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Sex-specific associations of sex hormone binding globulin and risk of bladder cancer

  • Junyong Ou , Hai Bi , Haobin Zhou , Zhanyi Zhang , Peichen Duan , Haoming Yin , Zezhen Zhou , Zhixin Xie , Xiaojun Tian , Jianfei Ye EMAIL logo and Shudong Zhang EMAIL logo
Published/Copyright: February 28, 2025
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Open Medicine
From the journal Open Medicine Volume 20 Issue 1

Abstract

Background

Males have a three times higher risk of a diagnosis of bladder cancer (Bca) than females. Sex hormone-binding globulin (SHBG) may be associated with Bca risk. However, the sex-specific role of SHBG in Bca remains unclear. In this study, we aimed to determine the role of SHBG in Bca.

Methods

A sex-specific univariable Mendelian randomization (MR) analysis involving 369,426 men and 395,375 women was conducted to assess the causal relationship between SHBG and testosterone and Bca risk. Sensitivity analyses and multivariable MR were conducted to confirm the robustness of our results. Linkage disequilibrium score regression assessed the genetic correlation between these diseases influenced by heredity.

Results

Univariable MR results showed that one-SD elevated SHBG was related to a low risk of Bca in males (OR: 0.60, 95% CI: 0.39–0.93; p = 0.022) but had no benefit in females. Genetically predicted BT was positively associated with Bca risk in males (OR: 1.59; 95% CI: 1.06–2.40; p  =  0.027). In multivariable MR, higher SHBG levels were not related to male Bca risk after controlling for BT.

Conclusions

Our findings do not provide evidence to support a causal relationship between SHBG and Bca risk in males although an association was observed in the univariable analysis. Further research is needed to identify the underlying pathways.

Keywords: bladder cancer; sex hormone binding globulin; risk; testosterone; genome-wide association studies

1 Introduction

Bladder cancer (Bca) is a common malignant tumor of the urinary system. It is a major economic burden on the healthcare system and is well known to be associated with sex bias [1]. Sex differences in Bca incidence have been observed in epidemiological and clinical studies, with a male-to-female risk ratio of 3:1 in terms of diagnosis [2,3]. Although smoking and exposure to occupational carcinogens are factors that contribute to the sex-dependent differences in Bca incidence, Bca still occurs in males after controlling exposure to these carcinogenic factors [4–6]. Therefore, intrinsic factors are likely to play key roles in urothelial carcinogenesis. Experimental and clinical evidence suggests the involvement of androgens and androgen receptors (AR) [7,8]. However, not all studies have reached unanimous conclusions.

Sex hormones and their receptors have been posited as potential contributory factors responsible for sex-based disparities in Bca incidence [9]. Androgens are likely to contribute to sexual dimorphism in Bca by directly and indirectly influencing various cellular processes, such as the synthesis of cytokines, growth factors, and vasoactive substances. Sex hormone-binding globulin (SHBG) is involved in binding to sex hormones and regulating their biological activity [2]. Nevertheless, establishing these associations conclusively through randomized controlled trials poses considerable challenges. Observational studies face difficulties in distinguishing the effects of SHBG levels from those attributable to sex hormones, given their intricate interrelationship. Furthermore, there is a lack of research investigating the sex-specific roles of SHBG in Bca.

To address the lack of experimental evidence for SHBG involvement in Bca, we used a Mendelian randomization (MR) study design, using naturally occurring genetic variants that affect SHBG levels throughout life [10]. Genetic variants are determined at conception; therefore, using this approach establishes the role of SHBG in Bca, excluding the potential confounding effects of socioeconomic position or other factors. This research utilized linkage disequilibrium score regression (LDSC) analysis of GWAS summary statistics to investigate the genetic associations among SHBG, BT, and Bca, with a focus on hereditary contributions. We conducted a sex-specific MR analysis using published single nucleotide polymorphisms (SNPs) to predict SHBG in both males and females and controlled for bioavailable testosterone (BT) levels.

2 Materials and methods

2.1 Genetic correlation analysis

LDSC is an effective method for analyzing genetic correlations [11]. We employed LDSC to examine the shared polygenic structure between diseases, complementing MR analysis. Linkage disequilibrium (LD) scores and weights for the European population were precomputed from 1,000 Genomes data by LDSC’s original developers. The analysis utilized the R package “ldscr.”

2.2 Research design

Initially, we employed univariate MR to evaluate the overall influence of SHBG and BT on Bca risk. Subsequently, we conducted a multivariable MR analysis to examine the direct and independent effects of these traits on the observed outcomes. This study followed the MR guidelines based on three key assumptions: a close relationship between genetic markers and SHBG, the independence of instrumental variables (IVs) from confounding factors, and the exclusive effect of IVs on Bca through SHBG [12] (Figure 1). The data utilized in this study were derived from publicly available genome-wide association studies (GWAS), which have been granted ethical approval and informed consent.

Figure 1 Study design. Bca: bladder cancer; SHBG: sex hormone-binding globulin.
Figure 1

Study design. Bca: bladder cancer; SHBG: sex hormone-binding globulin.

2.3 Data sources

2.3.1 Selection of genetic variants associated with exposure

In order to mitigate bias stemming from sample overlap, we utilized nonoverlapping datasets for each exposure-outcome pair. We selected SNPs from GWASs in the UK Biobank to serve as IVs for SHBG (GWAS ID: ieu-b-4871 for males, ieu-b-4870 for females) and BT (GWAS ID: ieu-b-4868 for males, ieu-b-4869 for females) of European ancestry [13]. SHBG genetic variations were derived from the UK Biobank’s summary sex-specific GWAS (185,221 white British males and 214,989 white British females). BT genetic variations were derived from the UK Biobank’s summary sex-specific GWAS (184,205 white British males and 180,386 white British females). We examined SNPs with genome-wide significance (p < 5 × 10−8) and utilized LD analysis to eliminate SNPs with mutual LD above the limit (LD clumping panel kb = 5,000, R 2 < 0.01) [14].

To address potential pleiotropy, we chose variables known to be involved with Bca. For instance, body mass index (BMI) might be a driver [15] or downstream factor [13] of SHBG. We used the PhenoScannerV2 (www.phenoscanner.medschl.ca.ac.uk) to exclude confounders, such as BMI, smoking, long-term exposure to industrial chemicals, arsenic contamination, chemotherapy drugs, such as cyclophosphamide, or pioglitazone for type 2 diabetes [5,16,17]. Finally, we included 48 and 66 SNPs as IVs for SHBG in males and females, respectively, and 53 and 77 SNPs as IVs for BT in males and females, respectively. To validate the strength of the identified SNPs, we produced F-statistics and conditional F-statistics for univariate and multivariable MR analyses.

2.3.2 Genetic variants associated with Bca

Summary data on the sex-specific genetic variants of Bca were obtained from FinnGen R10 comprising 175,121 European individuals (1,115 Bca cases and 174,006 controls) [18]. The GWAS analyses were adjusted for principal components.

2.3.3 Genetic variants for multivariable MR

We employed multivariable MR analysis to control for BT since SHBG was strongly related to this particular variable [13]. Genetic predictors of SHBG and BT were obtained from the UK Biobank. We excluded duplicate SNPs and those with a high correlation (r 2 > 0.05) using LDLink. The remaining SNPs were used for multivariable MR analysis.

2.3.4 Statistical analysis

The primary MR approach was inverse variance weighting (IVW), employed to assess the effect of a one-standard deviation (SD) increment in genetically predicted exposure on the outcome, which was reported as odds ratio (OR) accompanied by a 95% confidence interval (CI). Other MR methods, such as MR-Egger, weighted median, and weighted mode, were also used to investigate the consistency of effect estimates.

As a first step, SNPs with a genome-wide significance level of p < 5 × 10−8 and an F-statistic >10 were carefully selected. To address potential confounding factors, we utilized the PhenoScannerV2 website to exclude genetic confounders associated with Bca. For the assessment of heterogeneity and horizontal pleiotropy, Cochran’s Q statistic was employed to quantify heterogeneity, while radial MR was utilized to eliminate outliers [19]. Additionally, MR-Egger regression and the MR-Presso method were employed to evaluate the influence of horizontal pleiotropy upon effect estimations. Sensitivity analysis was conducted through leave-one-out tests to assess the effects of individual variants on the observed associations. For multivariable MR, the test for heterogeneity and pleiotropy were similar to those described above for univariate MR [20].

R2 indicates the proportion of SHBG variation that may be attributed to SNPs.

Furthermore, the required sample size for Bca events was estimated using the log OR, which measures the patient-to-non-patient ratio. All MR analyses were performed using the two-sample MR and MR packages in R (version 4.1.0).

3 Results

3.1 Genetic correlation analysis

The results of the genetic correlation analysis are presented in Table 1. We estimated a positive genetic correlation between the following pairs of diseases: SHBG (male) and Bca (male) (rg = 0.663, p-value = 1.52 × 10−05), SHBG (female) and Bca (female) (rg = 0.697, p-value = 7.95 × 10−58), and BT (male), and Bca (male) (rg = 0.563, p-value = 1.12 × 10−39).

Table 1

Results of genetic correlation analysis

Trait1 Trait2 Genetic correlation Standard error p-value
SHBG (male) Bca (male) 0.663 0.144 1.52 × 10−5
SHBG (female) Bca (female) 0.697 0.043 7.95 × 10−58
BT (male) Bca (male) 0.563 0.043 1.12 × 10−39
BT (female) Bca (female) −0.286 0.202 0.156

SHBG: sex hormone-binding globulin; BT: bioavailable testosterone; Bca: bladder cancer.

3.2 IVs

In the univariate MR analysis, we employed 48 and 66 genome-wide significant SNPs previously reported in males and females, respectively, for the assessment of SHBG. Furthermore, 53 and 77 genome-wide significant SNPs previously identified in males and females, respectively, were utilized for investigating BT. Following the methodology outlined by Burgess et al., all SNPs had an F-statistic exceeding >10, indicating the absence of weak instruments in univariate MR analysis (Table S1).

3.3 Causal effect of SHBG on Bca using univariable MR

The random-effects IVW approach was the main analytical method employed. In two sample MR, there was no indication of instrumental heterogeneity (Cochran’s Q test, p > 0.05). One SD elevated SHBG was related to a low risk of Bca in males OR: 0.60, 95% CI: 0.39–0.93; p = 0.022; Bonferroni’s correction [p = 0.05/2]). The causal effect estimation of the MR-Egger test and other methods were similar in direction and magnitude. However, genetically predicted SHBG had no association with Bca in females (OR: 1.32, 95% CI: 0.99–1.75 p = 0.061) (Figure 2).

Figure 2 Univariable MR results of SHBG using different methods. (a) The combined forest plot of SHBG on Bca. (b) The scatter plots of SHBG on Bca in males. (c) The scatter plots of SHBG on Bca in females. The number of genetic variants, OR, 95% CI, p values, and MR methods of associations are contained. SNPs(N): the number of single-nucleotide polymorphisms used as IVs; OR: the combined causal effect; CI: confidence interval; SHBG: sex hormone binding globulin; Bca: bladder cancer.
Figure 2

Univariable MR results of SHBG using different methods. (a) The combined forest plot of SHBG on Bca. (b) The scatter plots of SHBG on Bca in males. (c) The scatter plots of SHBG on Bca in females. The number of genetic variants, OR, 95% CI, p values, and MR methods of associations are contained. SNPs(N): the number of single-nucleotide polymorphisms used as IVs; OR: the combined causal effect; CI: confidence interval; SHBG: sex hormone binding globulin; Bca: bladder cancer.

One SD increase in BT was associated with a significantly increased Bca risk in males (OR: 1.59; 95% CI: 1.06–2.40; p  =  0.027). However, the result did not reach statistical significance after Bonferroni’s correction (p = 0.05/2), indicating a suggestive causal association. MR analyses, such as MR-Egger, weighted median, and weighted mode, were similar in direction and magnitude. In females, genetically predicted BT was unrelated to Bca (OR: 1.38, 95% CI: 0.94–2.02; p = 0.098) (Figure 3). The scatter plots of univariable MR analyses performed on FinnGen data using different methods showing the effect of exposure on Bca in male and female. The single MR effect of univariable MR analyses showing the effect of exposure on Bca is shown in Figure S1.

Figure 3 Univariable MR results of BT using different methods. (a) The combined forest plot of BT on Bca. (b) The scatter plots of BT on Bca in males. (c) The scatter plots of BT on Bca in females. The number of genetic variants, OR, 95% CI, p values, and MR methods of associations are contained. SNPs(N): the number of single-nucleotide polymorphisms used as IVs; OR: the combined causal effect; CI: confidence interval; Bca: bladder cancer.
Figure 3

Univariable MR results of BT using different methods. (a) The combined forest plot of BT on Bca. (b) The scatter plots of BT on Bca in males. (c) The scatter plots of BT on Bca in females. The number of genetic variants, OR, 95% CI, p values, and MR methods of associations are contained. SNPs(N): the number of single-nucleotide polymorphisms used as IVs; OR: the combined causal effect; CI: confidence interval; Bca: bladder cancer.

The MR-Egger intercept test was employed to assess pleiotropy. There was no directional pleiotropy found using MR-Egger regression or MR-PRESSO analysis (Table 2). The results of a leave-one-out sensitivity analysis demonstrated that no one SNP was responsible for the overall impact of sex hormones on Bca (Figure S2). The MR funnel diagram was symmetrical (Figure S3).

Table 2

Sensitive analyses result in univariable MR for Bca

Outcome Exposure IVW- Q test MR-Egger MR-Presso Global test
p-value Intercept SE p-value p-value
Bca
Male SHBG 0.987 −0.017 0.017 0.317 0.994
BT 0.849 0.011 0.015 0.463 0.816
Female SHBG 0.250 −0.003 0.009 0.779 0.312
BT 0.663 0.016 0.017 0.343 0.576

IVW: inverse-variance weighted; SE: standard error; SHBG: sex hormone-binding globulin; BT: bioavailable testosterone; Bca: bladder cancer.

3.4 Causal effect of SHBG on Bca using multivariable MR

After adjusting for BT in the multivariable MR for males, genetically predicted increased SHBG was not associated with the risk of Bca (OR: 1.08; 95% CI: 0.65–1.81; p  =  0.763). After controlling for SHBG, the causal relationship between BT and Bca did not remain statistically significant (OR: 0.85; 95% CI: 0.63–1.15; p  =  0.301) (Figure 4). The conditional F-statistics for the SHBG and BT were 40.2 and 95.0%, respectively. The conditional F-statistics indicated the absence of weak instruments in multivariable MR. Cochran’s Q statistic testing indicated the absence of heterogeneity in multivariable MR. Horizontal pleiotropy was not observed (Table 3). In direction and magnitude, the estimations were stable to the multivariable in MR-Egger, MR-Lasso, and MR-Presso approaches.

Figure 4 Multivariable MR results of SHBG and BT. The number of genetic variants, OR, 95% CI, p values, and MR methods of associations are contained. SNPs(N), the number of single-nucleotide polymorphisms used as IVs; OR, the combined causal effect; CI, confidence interval; p value, p value of the causal estimate; SHBG: sex hormone-binding globulin; Bca: bladder cancer; IVW: inverse variance weighted.
Figure 4

Multivariable MR results of SHBG and BT. The number of genetic variants, OR, 95% CI, p values, and MR methods of associations are contained. SNPs(N), the number of single-nucleotide polymorphisms used as IVs; OR, the combined causal effect; CI, confidence interval; p value, p value of the causal estimate; SHBG: sex hormone-binding globulin; Bca: bladder cancer; IVW: inverse variance weighted.

Table 3

Conditional F-statistics and sensitive analyses result in multivariable MR for Bca in males

Outcome Exposure F-statistics Q-test MR-Egger MR-Presso Global test
Q-statistic Q_p Intercept SE p-value p-value
Bca
SHBG 40.177 59.574 0.976 −0.006 0.008 0.431 0.977
BT 95.046

SE: standard error; SHBG: sex hormone-binding globulin; BT: bioavailable testosterone; Bca: bladder cancer.

4 Discussion

Understanding the influence of sex differences on the incidence, prevalence, and severity of Bca has become an increasingly important area of research. Sex should be regarded as a crucial biological variable to be included in future Bca research [21]. To the best of our knowledge, this study is the first to examine the sex-specific risk of Bca from a genetic perspective. We investigated the relationship between SHBG and Bca using univariate and multivariable MR analyses.

The glycoprotein SHBG is predominantly synthesized in the liver and exists as a homodimeric protein with a molecular weight of 90–100 kDa. Its binding ability extends to all androgens and estrogens, except for dehydroepiandrosterone sulfate and androstenedione. The free hormone hypothesis suggests that because binding proteins are the gatekeepers of steroid action, the biological activity of a hormone is best represented by the concentration of the free hormone rather than its total concentration. Notably, SHBG contributes considerably to the balance between free and protein-bound components of plasma and serves as a transporter of steroid hormones, facilitating their transport from the point of synthesis to their target location. Particularly for androgens, interactions with SHBG and albumin determine the delicate balance between bioavailability and total testosterone, thereby controlling tissue exposure. This balance can be influenced by factors such as aging, genetics, and various pathological conditions that affect target tissue hormone exposure [22]. Although the precise mechanism is yet unknown, it is conceivable that the regulatory function of SHBG in modulating the levels of free/BT in the bloodstream contributes to this protective association.

Additionally, SHBG may play a role in male Bca through other pathways. The development of Bca is influenced by inflammation in several ways. Chronic inflammation can cause DNA damage and mutations in bladder epithelial cells, thereby increasing the risk of Bca [23]. Bca cells can trigger an “inflammatory cytokine storm,” stimulating the secretion of tumor growth-promoting factors and weakening the cytotoxic function of immune cells. Cytokines and growth factors released by these cells may stimulate Bca cell proliferation [24]. Increased levels of reactive oxygen species, lipid peroxidation products, pro-inflammatory cytokines, and pro-angiogenic factors may induce inflammatory responses, ultimately activating Bca angiogenesis [25]. SHBG inhibits inflammation in vitro, which is not altered by co-supplementation with testosterone or estradiol [26], supporting a pathway through inflammation. Further investigation into potential pathways, especially those associated with sex-specific responses to SHBG and Bca, would be beneficial. Similarly, a meta-analysis of previous clinical trials showed that androgen deprivation therapy (ADT) may have antitumor effects on Bca [8]. However, these findings should be interpreted with caution. The relationship between ADT and Bca in previous observational studies has been inconsistent, and clinical trials to validate their efficacy are still lacking [7]. The efficacy of abiraterone and other approved anticancer agents for urothelial cancer in the treatment of Bca may be further elucidated through an ongoing clinical trial [27].

This study design has several strengths that contribute to the validity of our findings. This study adheres strictly to the assumptions of MR so that potential confounding factors and reverse causality are minimized, and an independent correlation between SHBG and Bca risk can be established. Moreover, LDSC aids in distinguishing true polygenic effects from confounding factors such as implicit associations and population stratification. Notably, this study is the first to comprehensively and systematically analyze prospective studies to evaluate the role of SHBG in Bca risk. We also employed MR-Egger, which provides robustness against pleiotropy, a potential limitation of MR. Replication with larger samples is required in such cases. Furthermore, the high F-statistics of the genetic instruments employed in this study mitigates concerns regarding the presence of weak instruments that could potentially introduce bias into our findings.

Despite its novelty, this study has several limitations. First, the research might have been influenced by survivorship bias and competing risks, which preclude the occurrence of Bca. We adjusted the common confounders of Bca. Second, compensatory processes or feedback mechanisms may dilute genetic effects, resulting in skewed MR estimations. However, this did not explain the observed beneficial association between SHBG and Bca. A common limitation is that non-muscle-invasive Bca is not distinguished from muscle-invasive disease. We could not stratify Bca across diagnostic types. Third, it is crucial to recognize a fundamental limitation of LDSC: while it indicates overall positive, negative, or absent genetic correlations, it does not account for mixed directional effects among shared genetic variants. We agree that the potential pleiotropic nature of the included variants and the shared genetic risk between SHBG and BT could distort the results. Consequently, additional research is needed to provide a more detailed quantification of polygenic overlap and deepen insights into the genetic interconnections between these diseases [28].

Regardless of the consistent and beneficial associations observed in this study, caution should be exercised when interpreting our findings [29]. Instead of focusing on the immediate results of an exogenous exposure, MR considers the long-term consequences of an endogenous one. Consequently, the impact on male Bca may not be significant in terms of factors that regulate SHBG.

Our findings do not provide evidence to support a causal relationship between SHBG and Bca risk in males. While an association was observed in the univariable analysis, this is likely influenced by shared genetic risk variants and the pleiotropic effects of the included variants. Further studies, including formal mediation analyses, are required to explore the potential interplay between SHBG, BT, and Bca risk.

Abbreviations

ADT

androgen deprivation therapy

AR

androgen receptor

Bca

bladder cancer

BMI

body mass index

CI

confidence interval

GWAS

genome-wide association study

IVs

instrumental variables

IVW

inverse variance-weighted

MR

Mendelian randomization

OR

odds ratio

SHBG

sex hormone-binding globulin

SNP

single nucleotide polymorphism

Acknowledgements

The authors acknowledge the efforts of the genome-wide association study consortia (GWAS) to provide high-quality resources for researchers.

  1. Funding information: This work was supported by the Beijing Natural Science Foundation (Z230014), the Key Clinical Projects of Peking University Third Hospital (BYSYFY2021046), and CSCO Clinical Oncology Research Foundation of Beijing (Y-tongshu2021/ms-0072).

  2. Author contributions: Conceptualization: J.Y.O., H.B., S.D.Z., J.F.Y.; search and evaluation: J.Y.O., H.B.Z., H.B.; data analysis: J.Y.O., H.B.Z., P.C.D., Z.Y.Z., Z.Z.Z., Z.X.X.; writing – original draft and visualization: J.Y.O., H.B.Z., P.C.D., Z.Y.Z., H.M.Y.; writing – review and revision: J.Y.O., S.D.Z., J.F.Y.; supervision and project management: S.D.Z., H.B., X.J.T.; resources: S.D.Z., H.B., J.F.Y., X.J.T.

  3. Conflict of interest: The authors declare that they have no conflicts of interest to disclose. This includes no financial or personal relationships with other people or organizations that could inappropriately influence the author’s work, including but not limited to employment, affiliation, grants, consultancies, honoraria, stock ownership, options, expert testimony, royalties, or patents.

  4. Data availability statement: The datasets for this study can be found in the GWAS Catalog [https://www.ebi.ac.uk/gwas/], FinnGen [https://www.finngen.fi/en], and Neale lab [http://www.nealelab.is/uk-biobank]. GWAS ID details can be found in methods or Supplementary Material.

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Received: 2024-05-09
Revised: 2025-01-24
Accepted: 2025-02-06
Published Online: 2025-02-28

© 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
  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. Review Articles
  156. The effects of enhanced external counter-pulsation on post-acute sequelae of COVID-19: A narrative review
  157. Diabetes-related cognitive impairment: Mechanisms, symptoms, and treatments
  158. Microscopic changes and gross morphology of placenta in women affected by gestational diabetes mellitus in dietary treatment: A systematic review
  159. Review of mechanisms and frontier applications in IL-17A-induced hypertension
  160. Research progress on the correlation between islet amyloid peptides and type 2 diabetes mellitus
  161. The safety and efficacy of BCG combined with mitomycin C compared with BCG monotherapy in patients with non-muscle-invasive bladder cancer: A systematic review and meta-analysis
  162. The application of augmented reality in robotic general surgery: A mini-review
  163. The effect of Greek mountain tea extract and wheat germ extract on peripheral blood flow and eicosanoid metabolism in mammals
  164. Neurogasobiology of migraine: Carbon monoxide, hydrogen sulfide, and nitric oxide as emerging pathophysiological trinacrium relevant to nociception regulation
  165. Plant polyphenols, terpenes, and terpenoids in oral health
  166. Laboratory medicine between technological innovation, rights safeguarding, and patient safety: A bioethical perspective
  167. End-of-life in cancer patients: Medicolegal implications and ethical challenges in Europe
  168. The maternal factors during pregnancy for intrauterine growth retardation: An umbrella review
  169. Intra-abdominal hypertension/abdominal compartment syndrome of pediatric patients in critical care settings
  170. PI3K/Akt pathway and neuroinflammation in sepsis-associated encephalopathy
  171. Screening of Group B Streptococcus in pregnancy: A systematic review for the laboratory detection
  172. Giant borderline ovarian tumours – review of the literature
  173. Leveraging artificial intelligence for collaborative care planning: Innovations and impacts in shared decision-making – A systematic review
  174. Cholera epidemiology analysis through the experience of the 1973 Naples epidemic
  175. Risk factors of frailty/sarcopenia in community older adults: Meta-analysis
  176. Supplement strategies for infertility in overweight women: Evidence and legal insights
  177. Scurvy, a not obsolete disorder: Clinical report in eight young children and literature review
  178. A meta-analysis of the effects of DBS on cognitive function in patients with advanced PD
  179. Protective role of selenium in sepsis: Mechanisms and potential therapeutic strategies
  180. Strategies for hyperkalemia management in dialysis patients: A systematic review
  181. C-reactive protein-to-albumin ratio in peripheral artery disease
  182. Case Reports
  183. Delayed graft function after renal transplantation
  184. Semaglutide treatment for type 2 diabetes in a patient with chronic myeloid leukemia: A case report and review of the literature
  185. Diverse electrophysiological demyelinating features in a late-onset glycogen storage disease type IIIa case
  186. Giant right atrial hemangioma presenting with ascites: A case report
  187. Laser excision of a large granular cell tumor of the vocal cord with subglottic extension: A case report
  188. EsoFLIP-assisted dilation for dysphagia in systemic sclerosis: Highlighting the role of multimodal esophageal evaluation
  189. Molecular hydrogen-rhodiola as an adjuvant therapy for ischemic stroke in internal carotid artery occlusion: A case report
  190. Coronary artery anomalies: A case of the “malignant” left coronary artery and its surgical management
  191. Rapid Communication
  192. Biological properties of valve materials using RGD and EC
  193. A single oral administration of flavanols enhances short-term memory in mice along with increased brain-derived neurotrophic factor
  194. Letter to the Editor
  195. Role of enhanced external counterpulsation in long COVID
  196. Expression of Concern
  197. Expression of concern “A ceRNA network mediated by LINC00475 in papillary thyroid carcinoma”
  198. Expression of concern “Notoginsenoside R1 alleviates spinal cord injury through the miR-301a/KLF7 axis to activate Wnt/β-catenin pathway”
  199. Expression of concern “circ_0020123 promotes cell proliferation and migration in lung adenocarcinoma via PDZD8”
  200. Corrigendum
  201. Corrigendum to “Empagliflozin improves aortic injury in obese mice by regulating fatty acid metabolism”
  202. Corrigendum to “Comparing the therapeutic efficacy of endoscopic minimally invasive surgery and traditional surgery for early-stage breast cancer: A meta-analysis”
  203. Corrigendum to “The progress of autoimmune hepatitis research and future challenges”
  204. Retraction
  205. Retraction of “miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway”
  206. Retraction of: “LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through downregulating SP-A by sponging to miR-424”
  207. Retraction of: “SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways”
  208. Special Issue Advancements in oncology: bridging clinical and experimental research - Part II
  209. Unveiling novel biomarkers for platinum chemoresistance in ovarian cancer
  210. Lathyrol affects the expression of AR and PSA and inhibits the malignant behavior of RCC cells
  211. The era of increasing cancer survivorship: Trends in fertility preservation, medico-legal implications, and ethical challenges
  212. Bone scintigraphy and positron emission tomography in the early diagnosis of MRONJ
  213. Meta-analysis of clinical efficacy and safety of immunotherapy combined with chemotherapy in non-small cell lung cancer
  214. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part IV
  215. Exploration of mRNA-modifying METTL3 oncogene as momentous prognostic biomarker responsible for colorectal cancer development
  216. Special Issue The evolving saga of RNAs from bench to bedside - Part III
  217. Interaction and verification of ferroptosis-related RNAs Rela and Stat3 in promoting sepsis-associated acute kidney injury
  218. The mRNA MOXD1: Link to oxidative stress and prognostic significance in gastric cancer
  219. Special Issue Exploring the biological mechanism of human diseases based on MultiOmics Technology - Part II
  220. Dynamic changes in lactate-related genes in microglia and their role in immune cell interactions after ischemic stroke
  221. A prognostic model correlated with fatty acid metabolism in Ewing’s sarcoma based on bioinformatics analysis
  222. Red cell distribution width predicts early kidney injury: A NHANES cross-sectional study
  223. Special Issue Diabetes mellitus: pathophysiology, complications & treatment
  224. Nutritional risk assessment and nutritional support in children with congenital diabetes during surgery
  225. Correlation of the differential expressions of RANK, RANKL, and OPG with obesity in the elderly population in Xinjiang
  226. A discussion on the application of fluorescence micro-optical sectioning tomography in the research of cognitive dysfunction in diabetes
  227. A review of brain research on T2DM-related cognitive dysfunction
  228. Metformin and estrogen modulation in LABC with T2DM: A 36-month randomized trial
  229. Special Issue Innovative Biomarker Discovery and Precision Medicine in Cancer Diagnostics
  230. CircASH1L-mediated tumor progression in triple-negative breast cancer: PI3K/AKT pathway mechanisms
https://doi.org/10.1515/med-2025-1163
Keywords for this article
bladder cancer; sex hormone binding globulin; risk; testosterone; genome-wide association studies
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. Review Articles
  156. The effects of enhanced external counter-pulsation on post-acute sequelae of COVID-19: A narrative review
  157. Diabetes-related cognitive impairment: Mechanisms, symptoms, and treatments
  158. Microscopic changes and gross morphology of placenta in women affected by gestational diabetes mellitus in dietary treatment: A systematic review
  159. Review of mechanisms and frontier applications in IL-17A-induced hypertension
  160. Research progress on the correlation between islet amyloid peptides and type 2 diabetes mellitus
  161. The safety and efficacy of BCG combined with mitomycin C compared with BCG monotherapy in patients with non-muscle-invasive bladder cancer: A systematic review and meta-analysis
  162. The application of augmented reality in robotic general surgery: A mini-review
  163. The effect of Greek mountain tea extract and wheat germ extract on peripheral blood flow and eicosanoid metabolism in mammals
  164. Neurogasobiology of migraine: Carbon monoxide, hydrogen sulfide, and nitric oxide as emerging pathophysiological trinacrium relevant to nociception regulation
  165. Plant polyphenols, terpenes, and terpenoids in oral health
  166. Laboratory medicine between technological innovation, rights safeguarding, and patient safety: A bioethical perspective
  167. End-of-life in cancer patients: Medicolegal implications and ethical challenges in Europe
  168. The maternal factors during pregnancy for intrauterine growth retardation: An umbrella review
  169. Intra-abdominal hypertension/abdominal compartment syndrome of pediatric patients in critical care settings
  170. PI3K/Akt pathway and neuroinflammation in sepsis-associated encephalopathy
  171. Screening of Group B Streptococcus in pregnancy: A systematic review for the laboratory detection
  172. Giant borderline ovarian tumours – review of the literature
  173. Leveraging artificial intelligence for collaborative care planning: Innovations and impacts in shared decision-making – A systematic review
  174. Cholera epidemiology analysis through the experience of the 1973 Naples epidemic
  175. Risk factors of frailty/sarcopenia in community older adults: Meta-analysis
  176. Supplement strategies for infertility in overweight women: Evidence and legal insights
  177. Scurvy, a not obsolete disorder: Clinical report in eight young children and literature review
  178. A meta-analysis of the effects of DBS on cognitive function in patients with advanced PD
  179. Protective role of selenium in sepsis: Mechanisms and potential therapeutic strategies
  180. Strategies for hyperkalemia management in dialysis patients: A systematic review
  181. C-reactive protein-to-albumin ratio in peripheral artery disease
  182. Case Reports
  183. Delayed graft function after renal transplantation
  184. Semaglutide treatment for type 2 diabetes in a patient with chronic myeloid leukemia: A case report and review of the literature
  185. Diverse electrophysiological demyelinating features in a late-onset glycogen storage disease type IIIa case
  186. Giant right atrial hemangioma presenting with ascites: A case report
  187. Laser excision of a large granular cell tumor of the vocal cord with subglottic extension: A case report
  188. EsoFLIP-assisted dilation for dysphagia in systemic sclerosis: Highlighting the role of multimodal esophageal evaluation
  189. Molecular hydrogen-rhodiola as an adjuvant therapy for ischemic stroke in internal carotid artery occlusion: A case report
  190. Coronary artery anomalies: A case of the “malignant” left coronary artery and its surgical management
  191. Rapid Communication
  192. Biological properties of valve materials using RGD and EC
  193. A single oral administration of flavanols enhances short-term memory in mice along with increased brain-derived neurotrophic factor
  194. Letter to the Editor
  195. Role of enhanced external counterpulsation in long COVID
  196. Expression of Concern
  197. Expression of concern “A ceRNA network mediated by LINC00475 in papillary thyroid carcinoma”
  198. Expression of concern “Notoginsenoside R1 alleviates spinal cord injury through the miR-301a/KLF7 axis to activate Wnt/β-catenin pathway”
  199. Expression of concern “circ_0020123 promotes cell proliferation and migration in lung adenocarcinoma via PDZD8”
  200. Corrigendum
  201. Corrigendum to “Empagliflozin improves aortic injury in obese mice by regulating fatty acid metabolism”
  202. Corrigendum to “Comparing the therapeutic efficacy of endoscopic minimally invasive surgery and traditional surgery for early-stage breast cancer: A meta-analysis”
  203. Corrigendum to “The progress of autoimmune hepatitis research and future challenges”
  204. Retraction
  205. Retraction of “miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway”
  206. Retraction of: “LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through downregulating SP-A by sponging to miR-424”
  207. Retraction of: “SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways”
  208. Special Issue Advancements in oncology: bridging clinical and experimental research - Part II
  209. Unveiling novel biomarkers for platinum chemoresistance in ovarian cancer
  210. Lathyrol affects the expression of AR and PSA and inhibits the malignant behavior of RCC cells
  211. The era of increasing cancer survivorship: Trends in fertility preservation, medico-legal implications, and ethical challenges
  212. Bone scintigraphy and positron emission tomography in the early diagnosis of MRONJ
  213. Meta-analysis of clinical efficacy and safety of immunotherapy combined with chemotherapy in non-small cell lung cancer
  214. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part IV
  215. Exploration of mRNA-modifying METTL3 oncogene as momentous prognostic biomarker responsible for colorectal cancer development
  216. Special Issue The evolving saga of RNAs from bench to bedside - Part III
  217. Interaction and verification of ferroptosis-related RNAs Rela and Stat3 in promoting sepsis-associated acute kidney injury
  218. The mRNA MOXD1: Link to oxidative stress and prognostic significance in gastric cancer
  219. Special Issue Exploring the biological mechanism of human diseases based on MultiOmics Technology - Part II
  220. Dynamic changes in lactate-related genes in microglia and their role in immune cell interactions after ischemic stroke
  221. A prognostic model correlated with fatty acid metabolism in Ewing’s sarcoma based on bioinformatics analysis
  222. Red cell distribution width predicts early kidney injury: A NHANES cross-sectional study
  223. Special Issue Diabetes mellitus: pathophysiology, complications & treatment
  224. Nutritional risk assessment and nutritional support in children with congenital diabetes during surgery
  225. Correlation of the differential expressions of RANK, RANKL, and OPG with obesity in the elderly population in Xinjiang
  226. A discussion on the application of fluorescence micro-optical sectioning tomography in the research of cognitive dysfunction in diabetes
  227. A review of brain research on T2DM-related cognitive dysfunction
  228. Metformin and estrogen modulation in LABC with T2DM: A 36-month randomized trial
  229. Special Issue Innovative Biomarker Discovery and Precision Medicine in Cancer Diagnostics
  230. CircASH1L-mediated tumor progression in triple-negative breast cancer: PI3K/AKT pathway mechanisms
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