Home Medicine No genetic causality between obesity and benign paroxysmal vertigo: A two-sample Mendelian randomization study
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No genetic causality between obesity and benign paroxysmal vertigo: A two-sample Mendelian randomization study

  • Zhiyan Guo , Bingyu Huang , Lingxiao Gan , Shanshan Liang and Ying Liu EMAIL logo
Published/Copyright: April 5, 2024
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Open Medicine
From the journal Open Medicine Volume 19 Issue 1

Abstract

Objective:

We applied Mendelian randomization to explore the causal relationship between obesity and benign paroxysmal vertigo (BPV).

Methods:

We chose two types of obesity diseases. Obesity due to excessive calories and other or unspecified obesity from the FinnGen database. We used genomic significance (p < 5 × 10−8) to obtain independent single nucleotide polymorphisms (SNPs) as instrumental variables. Similarly, genome-wide association study data for the disease BPV were selected from the FinnGen database. R was then used to test the data for multiplicity and heterogeneity, as well as to detect the effect of individual SNPs on the results. Random effects inverse variance weighting was used as the main statistical analysis.

Results:

First, by analyzing, we found an outlier in obesity due to excessive calories (rs12956821). Outliers were then removed, and the statistical results were analyzed without heterogeneity (p > 0.05) and horizontal pleiotropy (p > 0.05), as well as individual SNPs having no effect on the results. Meanwhile, random-effects IVW results showed obesity due to excessive calories (p = 0.481; OR = 0.941), and other or unspecified obesity (p = 0.640; OR = 0.964).

Conclusions:

The present study did not find a causal relationship between the above two obesity types and BPV at the genetic level.

Keywords: obesity; benign paroxysmal vertigo; genome-wide association study; Mendelian randomization

1 Introduction

Benign paroxysmal vertigo (BPV) is a common form of vertigo and is also one of the most common forms of peripheral vestibular dysfunction seen in clinical practice. With a lifetime frequency of 2.4%, the illness is categorized as primary or secondary and has a significant recurrence rate [1]. Patients typically experience vertigo and nystagmus symptoms as a result of head position changes [2]. At present, the pathogenesis of BPV is not fully understood, and the etiology of the disease is unknown in most patients and is generally thought to be related to the production of abnormal otoliths in the semicircular canals [3]. Researchers have shown that a number of risk factors, including old age, head trauma, Meniere’s illness, vascular disease, and vitamin D insufficiency, have an impact on the recurrence rate of BPV [4]. Metabolic diseases such as osteoporosis, type I diabetes, hyperlipidemia, gout, and hypertension are strong risk factors for BPV [5]. However, there is currently a lack of consensus and insufficient study on these risk variables [6].

Over the past few decades, there has been a sharp rise in obesity, a metabolic disorder that puts human health at risk [7]. A body mass index of greater than 30 is currently considered the definition of obesity [8]. Excessive caloric consumption, physical activity, and a complex web of social, environmental, and genetic variables all play a role in the development of obesity [9,10]. In people who are genetically predisposed to fat storage, imbalanced energy intake and expenditure often manifest more pronouncedly. This could be due to interactions between brain rewards and homeostatic circuits [11].

Type 1 diabetes, cardiovascular disease, metabolic syndrome, chronic renal disease, hyperlipidemia, hypertension, and several cancers are among the illnesses that obesity increases the risk of developing [12]. Similar to this, a number of metabolic conditions are conducive to the development of BPV [5]. In addition, obesity and BPV seem to be connected in some way based on recent clinical practice observations [13–15]. Determining whether obesity development can increase the likelihood of the occurrence and recurrence of BPV, as well as elucidating the connection between obesity and BPV, becomes crucial. Given the dearth of studies in this area at the moment and the difficulties in running clinical randomized controlled trials. We planned to investigate the genetic basis of the causal relationship between obesity and BPV using Mendelian randomized genome-wide association studies (GWAS) [16–19].

Mendelian randomization (MR) study designs follow Mendel’s laws of inheritance, which state that if a genotype determines a phenotype, then that genotype can be associated with a disease through that phenotype. In order to explore the association between phenotype and disease or between illness and disease, genotype might be employed as an instrumental variable (IV) [20]. Studies using MR can also avoid the effects of confounding variables that were present in earlier clinical studies [21]. GWAS have identified more than 100 independent genes associated with common obesity states in large samples [22]. Genetic variants linked to a higher risk of obesity have been found in several recent GWAS in large patient samples [23]. In order to investigate the relationship between obesity and BPV, two types of obesity (obesity due to excessive calories and other or unspecified obesity) were chosen from the GWAS database.

2 Methods

2.1 GWAS summary data for obesity due to excess calories and other or unspecified obesity

Maximum GWAS summary data were chosen from the FinnGen database (https://r9.finngen.fi), including obesity due to excessive calories and other or unspecified obesity [24]. The 370,945 participants in the obesity due to excessive calories type of study included 15,045 in the case group, 355,902 in the control group, and a total of 20,170,080 single nucleotide polymorphisms (SNPs). The 366,927 participants in the other type of obesity study were from Europe, with 11,025 in the case group and 355,902 in the control group, for a total of 20,170,026 SNPs. The International Classification of Diseases, Tenth Edition (ICD-10) codes E66.0 and E66.8/E66.9 were used to define two distinct types of obesity, and two distinct types of obesity-associated SNPs were used as genetic IVs, respectively, obesity due to excess calories and other or unspecified obesity. For more information on participants, genotyping, interpolation, and quality control, visit the FinnGen Web site (https://risteys.finregistry.fi/endpoints/E4_OBESITYCAL) and (https://risteys.finregistry.fi/endpoints/E4_OBESITYNAS).

2.2 GWAS summary data for BPV

The largest BPV’s GWAS summary data were chosen from the FinnGen database (https://r9.finngen.fi) [24]. The 367,374 European participants in this GWAS included 8,280 in the case group and 359,094 in the control group, for a total of 20,170,074 SNPs. The International Classification of Diseases, 10th edition (ICD-10) codes for H81.8 were used to define all cases. For more information on BPV regarding participants, genotyping, interpolation, and quality control, visit the FinnGen website (https://risteys.finregistry.fi/endpoints/H8_BPV).

2.3 Genetic instrumental variants selection

As IVs for the study, two types of obesity (obesity due to excess calories and other or unspecified obesity) were chosen. The IVs chosen for this study satisfy the three hypotheses of MR analysis: IVs and exposure factors are related, IVs are not related to confounders, and IVs influence outcomes through exposure factors. First, we identified important SNPs for both forms of obesity using the genome-wide significance of p < 5 × 10−8. Then, r 2 < 0.001 and clumping distance = 10,000 kb were used to eliminate the strong LD-induced chaining imbalance between SNPs. Then, we eliminated SNPs associated with BPV (p < 1 × 10−5). After conducting a literature search, we discovered the following confounding factors associated with BPV: female gender, hypertension, diabetes, hyperlipidemia, osteoporosis, and vitamin D defenses [4,25,26]. Confounding variables were eliminated using the PhenoScanner database [27]. The intermediate allele frequency palindromic SNPs were then removed. Additionally, we chose SNPs with F-statistics >10 as IVs to ensure a greater correlation between IVs and exposure [28]. F = β 2/SE2 was used to calculate the F statistic [29]. Use the formula R 2 = (2 × EAF × (1 − EAF) × β 2)/[(2 × EAF × (1 − EAF) × β 2) + (2 × EAF × (1 − EAF) × N × SE2] to calculate R 2 [30], where β represents the estimated genetic influence on obesity and SE represents the genetic influence’s standard error. In the GWAS for the SNP-obesity connection, N is the sample size and EAF is the impact allele frequency. In the end, we obtained eight SNPs associated with obesity due to excessive calories and six SNPs associated with other or unspecified obesity (Table 1). Before getting obesity due to excessive calories SNPs, we excluded three palindromic SNPs (rs12507026, rs2076308, rs4517468), six confounding SNPs (rs1446585, rs6567160, rs9928094, rs1861410, rs2867131, rs7189927), and no SNPs associated with BPV existed, and these eight SNPs were used as IV (F-statistics >10). Before getting other or unspecified obesity SNPs, we excluded six confounding SNPs (rs11030104, rs7563362, rs10938398, rs538656, rs62048402, rs72892910), the absence of BPV-associated SNPs, and palindromic SNPs, of which six were used as IV (F-statistics >10).

Table 1

Obesity genetic IVs in benign paroxysmal positional vertigo GWAS

SNP EA NEA EAF β SE p β SE p
Exposure (obesity due to excess calories) GWAS Outcome (BPV) GWAS
rs12956821 G T 0.359 −0.070 0.012 1.54 × 10−8 −0.052 0.017 0.001
rs1595215 G A 0.230 −0.083 0.014 6.71 × 10−9 −0.011 0.019 0.575
rs17587238 A G 0.080 0.121 0.021 1.05 × 10−8 −0.029 0.029 0.324
rs34783010 T G 0.259 −0.088 0.014 1.23 × 10−10 −0.006 0.018 0.748
rs3972483 A C 0.215 0.096 0.014 1.38 × 10−11 −0.014 0.019 0.465
rs5011431 A G 0.346 0.069 0.012 2.36 × 10−8 0.016 0.017 0.327
rs72546309 T C 0.104 −0.111 0.020 2.90 × 10−8 0.026 0.026 0.316
rs826583 G A 0.214 0.079 0.014 2.88 × 10−8 −0.021 0.019 0.285
Exposure (Other or unspecified obesity) GWAS Outcome (BPV) GWAS
rs10938398 A G 0.472 0.091 0.014 4.19 × 10−11 0.035 0.016 0.029
rs11030104 G A 0.166 −0.104 0.019 3.59 × 10−8 0.032 0.021 0.133
rs13030967 G A 0.616 0.085 0.014 2.83 × 10−9 −0.001 0.016 0.933
rs2300861 T C 0.545 −0.081 0.014 5.12 × 10−9 −0.026 0.016 0.098
rs3734555 A G 0.331 0.091 0.014 2.76 × 10−10 −0.022 0.017 0.185
rs4289073 T G 0.567 −0.086 0.014 5.14 × 10−10 0.016 0.016 0.306
rs67553175 A G 0.208 0.115 0.017 5.14 × 10−12 −0.015 0.020 0.451
rs7563362 G A 0.854 0.153 0.020 4.42 × 10−14 −0.021 0.022 0.351
rs888154 A C 0.332 −0.086 0.015 6.38 × 10−9 −0.001 0.017 0.957

Abbreviations: GWAS, genome‐wide association study; SNP, single‐nucleotide polymorphism; EA, effect allele; NEA, non‐effect allele; EAF, effect allele frequency; β, the size of the obesity effect allele’s regression coefficient; SE, standard error; BPV, benign paroxysmal vertigo.

2.4 Statistical and MR analysis

2.4.1 Association of obesity genetic IVs with BPV GWAS

From two obesity GWAS pooled datasets, we retrieved eight and nine separate genetic IVs. The results showed a correlation between each genetic IV and the GWAS for BPV (Table 1).

2.4.2 Pleiotropy and heterogeneity test

Using the TwoSampleMR and MRPRESSO packages in R (version 4.3.1), we conducted a two-sample MR analysis of obesity and BPV [31]. MR Egger’s intercept test and the MR-PRESSO method were used to detect horizontal pleiotropy [32,33]. The p > 0.05 shows that the IV for the obesity gene does not have horizontal pleiotropy for GWAS for BPV. The Cochran and Rucker Q statistic were used to detect heterogeneity in the MR analysis [34,35], with p > 0.05 indicating no heterogeneity. The distortion test for MR-PRESSO analysis was used to detect the presence of outliers in our MR analysis, which usually have an impact on the heterogeneity of the data. We need to reanalyze the results after removing the outliers [32].

2.4.3 MR analysis

The mr_egger, weighted median, inverse variance weighting (IVW), simple mode, and weighted mode methods were used to analyze the causal relationship between obesity and BPV. We mainly used the results of IVW as the primary basis [36]. The mr_egger, weighted median, simple mode, and weighted mode methods were used as a basis for ancillary judgments [37,38]. Obesity and BPV are causally related when p < 0.05.

2.4.4 Single SNP effect analysis

We used “mr_scatter_plot” in R to verify the causal relationship between obesity and BPV [39]. “mr_forest_plot” was used to determine individual SNP effect sizes in the effect of obesity on BPV [40]. The “mr_leaveoneout_plot” sensitivity analysis to determine whether the relationship between obesity and BPV is affected by each SNP [41].

  1. Ethics approval and consent to participate: Ethical review approval has been obtained for the Finnish study. The present study was analyzed using information from its database. No additional ethical review approval was required.

3 Results

3.1 Pleiotropy and heterogeneity of obesity genetic IVs

First, in the MR analysis between obesity due to excess calories and BPV by MR-PRESSO, we found an outlier (rs12956821). The analysis between other obesity or obesity of unknown type and BPV did not show any outliers. Finally, the analysis of the results of removing outliers continues. The results showed no horizontal pleiotropy or heterogeneity for each obesity type and BPV (Table 2).

Table 2

Tests of pleiotropy and heterogeneity of genetic instrumental variants for two types of obesity

mr_egger PRESSO mr_egger IVW
Intercept SE p p Q Q_df p Q Q_df p
Pleiotropy test (obesity due to excess calories genetic IVs) Heterogeneity test (obesity due to excess calories genetic IVs)
0.068 0.045 0.192 0.628 2.268 5 0.811 18.871 6 0.605
Pleiotropy test (other or unspecified obesity genetic IVs) Heterogeneity test (other or unspecified obesity genetic IVs)
0.071 0.063 0.321 0.362 4.278 4 0.370 5.650 5 0.342

Abbreviations: GWAS, genome‐wide association study; IVW, inverse variance weighted; MR, Mendelian randomization; SE, standard error.

p > 0.05 represents no significant pleiotropy and heterogeneity.

3.2 Obesity was not associated with BPV

We used MR analysis to determine the causal relationship between the two types of obesity and BPV at the gene level after removing the outliers. IVW (β = −0.060; p = 0.481; odds ratio [OR] = 0.941; 95% confidence interval [95% CI]: 0.796–1.113) analyzed the causality results of obesity due to excess calories and BPV, and other tests similarly supported IVW’s results. IVW (β = −0.037; p = 0.640; OR = 0.964; 95% CI: 0.825–1.125) analyzed the causality results of other or unspecified obesity and BPV, and other tests similarly support IVW’s results (Table 3). In summary, our analyses show that there is no connection between genetic alterations in obesity brought on by obesity due to excess calories and other or unspecified obesity for BPV.

Table 3

Causal association of obesity with BPV

Method N β SE p OR 95% CI
Obesity due to excess calories
mr_egger 7 −0.821 0.512 0.170 0.440 0.161–1.201
Weighted median 7 −0.106 0.108 0.326 0.899 0.728–1.111
IVW 7 −0.060 0.085 0.481 0.941 0.796–1.113
Simple mode 7 −0.224 0.179 0.258 0.800 0.563–1.136
Weighted mode 7 −0.213 0.176 0.273 0.808 0.572–1.142
Other or unspecified obesity
mr_egger 6 −0.843 0.703 0.296 0.430 0.109–1.705
Weighted median 6 −0.091 0.093 0.327 0.913 0.760–1.096
IVW 6 −0.052 0.081 0.521 0.949 0.809–1.113
Simple mode 6 −0.133 0.147 0.408 0.876 0.656–1.169
Weighted mode 6 −0.137 0.139 0.368 0.872 0.664–1.144

Abbreviations: IVW, inverse variance weighted; MR, Mendelian randomization; N, number of single‐nucleotide polymorphism; β, the size of the obesity effect allele’s regression coefficient; SE, standard error; OR, odds ratio; 95%CI, 95% confidence interval; BPV, benign paroxysmal vertigo. p < 0.05 indicates a causal relationship between obesity and BPV.

3.3 No significant bias in single obesity SNP effect

It was shown by MR analysis that the effect of each SNP change on obesity does not have an effect on BPV (Figure 1). The same is demonstrated for the studies of the individual SNP effect values (Figure 2). At the same time, the leave-one-out sensitivity analysis we performed showed that the final results did not receive an effect when we removed any obese SNP (Figure 3).

Figure 1 Individual estimates about the putative causal effect of obesity on BPV. (a) Obesity due to excess calories and benign paroxysmal vertigo. (b) Other or unspecified obesity and benign paroxysmal vertigo. IVW, inverse variance weighted; MR, Mendelian randomization; SNP, single‐nucleotide polymorphism. BPV, benign paroxysmal vertigo.
Figure 1

Individual estimates about the putative causal effect of obesity on BPV. (a) Obesity due to excess calories and benign paroxysmal vertigo. (b) Other or unspecified obesity and benign paroxysmal vertigo. IVW, inverse variance weighted; MR, Mendelian randomization; SNP, single‐nucleotide polymorphism. BPV, benign paroxysmal vertigo.

Figure 2 Forest plot of obesity associated with BPV. (a) Obesity due to excess calories and benign paroxysmal vertigo. (b) Other or unspecified obesity and benign paroxysmal vertigo. MR, Mendelian randomization. BPV, benign paroxysmal vertigo.
Figure 2

Forest plot of obesity associated with BPV. (a) Obesity due to excess calories and benign paroxysmal vertigo. (b) Other or unspecified obesity and benign paroxysmal vertigo. MR, Mendelian randomization. BPV, benign paroxysmal vertigo.

Figure 3 MR leave‐one‐out sensitivity analysis for the effect of obesity SNPs on BPV. (a) Obesity due to excess calories and benign paroxysmal vertigo. (b) Other or unspecified obesity and benign paroxysmal vertigo. MR, Mendelian randomization; SNP, single‐nucleotide polymorphism. BPV, benign paroxysmal vertigo.
Figure 3

MR leave‐one‐out sensitivity analysis for the effect of obesity SNPs on BPV. (a) Obesity due to excess calories and benign paroxysmal vertigo. (b) Other or unspecified obesity and benign paroxysmal vertigo. MR, Mendelian randomization; SNP, single‐nucleotide polymorphism. BPV, benign paroxysmal vertigo.

4 Discussion

In this study, we explored the causal relationship between obesity and BPV at the genetically inherited level. After effective screening of SNPs and removal of outliers using MR and using obesity-associated SNPs as our genetic IVs, we analyzed that there was no horizontal pleiotropy (p > 0.05) or heterogeneity (p > 0.05) in the SNPs for the two obesity types and BPV, respectively. Meanwhile, we found that all five MR analyses, mainly IVW, showed that the two types of obesity, obesity due to excess calories and other or unspecified obesity, respectively, were not causally correlated genetically with BPV (p > 0.05).

Clinically, we observe that patients with BPV tend to be elderly, female, and have metabolic disorders such as diabetes mellitus, hypertension, hyperlipidemia, and osteoporosis [42]. These factors that contribute to BPV are commonly associated with the onset and progression of obesity. Despite the fact that there is little in-depth literature on the subject, there is also no literature that negates the existence of a relationship between the two. Only a few observational studies have explored the existence of a relationship and the fact that obesity is sometimes used as a confounding factor in exploring vertigo with other disorders [43–46]. At the same time, it is widely recognized in research that obesity is a high-risk predisposing factor for a variety of diseases. Therefore, there has been ambiguity in defining whether there is some association between obesity and BPV and the magnitude of the association. Limitations in conducting clinical trials exploring the relationship seem to have created an obstacle in resolving this issue. In recent years, with the widespread use of MR experiments, we have found ideas to solve the problem. Since parental alleles are randomly assigned to offspring, single nucleotide site variants can be more appropriately used to genetically explore the relationship between obesity and BPV [47]. However, at the genetic level, this study did not find a significant causal relationship between the two. BPV is one of the many vertigo disorders; other vertigo disorders include vestibular neuritis, Meniere’s disease, central vertigo, and others [48]. Similarly, obesity, as we know it, possesses multiple types. It has been shown that obesity negatively affects residual dizziness in BPV patients after otolith repositioning operations [13]. Additionally, in studies of adults with and without dizziness or vertigo, the difference in body mass index and obesity was found to be significantly higher in the group with dizziness [14]. Thus, some studies have observed an association between obesity and vertigo. Metabolic disorders such as hypertension, diabetes, and hyperlipidemia associated with obesity can cause cerebrovascular atherosclerosis as well as the development of insufficient arterial blood supply, which can cause vertigo. There are no more refined studies exploring the relationship between BPV and obesity at the clinical and genetic levels. In this study, BPV, obesity due to excess calories, and other or unspecified obesity were selected as relatively common types of vertigo and obesity. The relationship between BPV and obesity due to excess calories and other or unspecified obesity was explored. The number of obese patients is increasing today, and the adverse effects on them are manifold. Although this study did not conclude that there is a genetic and hereditary association between obesity and BPV, we cannot ignore other clinical effects that obesity may have on the occurrence and recurrence of BPV.

5 Limitations

There are also some limitations to this study. First, since the gene IVs for obesity and the GWAS for BPV are of European origin, the results of the study may not necessarily be genetically relevant for populations of other origins. Second, since only the two most common types of obesity (obesity due to excess calories and other or unspecified obesity) were selected in this study, it does not have much significance as a guide for other types of obesity, such as drug-induced obesity and obesity hypoventilation syndrome. Next, future clinical trials are necessary in this study to further elucidate that there is no causal relationship between obesity and BPV.

6 Conclusion

Although our analyses did not indicate a causal relationship between obesity due to excess calories and other or unspecified obesity and BPV in terms of genetic inheritance, we cannot rule out the existence of some unknown relationship between the two at the non-genetic level. Therefore, a broader and deeper investigation of the relationship is needed in the future.

Abbreviations

BPV

benign paroxysmal vertigo

EAF

effect allele frequency

GWAS

genome-wide association study

IVs

instrumental variables

IVW

inverse variance weighting

MR

Mendelian randomization

OR

odds ratio

SE

standard error

SNPs

single nucleotide polymorphisms

95% CI

95% confidence interval

tel: +86-13977175003

Acknowledgements

The authors would like to acknowledge the participants and investigators of the FinnGen study.

  1. Funding information: This study was supported by a grant from the National Natural Science Foundation of China (82360456,81901394).

  2. Author contributions: Ying Liu and Zhiyan Guo designed the study; Zhiyan Guo and Bingyu Huang wrote the manuscript; Zhiyan Guo, Lingxiao Gan, and Shanshan Liang performed the statistical analysis. All authors agreed to the published version of the manuscript.

  3. Conflict of interest: No relevant disclosures.

  4. Data availability statement: All datasets generated and/or analyzed during the current study are available in the FinnGen repository (https://r9.finngen.fi). The analyzed code in R can be found on the website (https://mrcieu.github.io/TwoSampleMR/articles/index.html).

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Received: 2023-11-23
Revised: 2024-02-04
Accepted: 2024-03-04
Published Online: 2024-04-05

© 2024 the author(s), published by De Gruyter

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

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https://doi.org/10.1515/med-2024-0940
Keywords for this article
obesity; benign paroxysmal vertigo; genome-wide association study; Mendelian randomization
Creative Commons
BY 4.0

Articles in the same Issue

  1. Research Articles
  2. EDNRB inhibits the growth and migration of prostate cancer cells by activating the cGMP-PKG pathway
  3. STK11 (LKB1) mutation suppresses ferroptosis in lung adenocarcinoma by facilitating monounsaturated fatty acid synthesis
  4. Association of SOX6 gene polymorphisms with Kashin-Beck disease risk in the Chinese Han population
  5. The pyroptosis-related signature predicts prognosis and influences the tumor immune microenvironment in dedifferentiated liposarcoma
  6. METTL3 attenuates ferroptosis sensitivity in lung cancer via modulating TFRC
  7. Identification and validation of molecular subtypes and prognostic signature for stage I and stage II gastric cancer based on neutrophil extracellular traps
  8. Novel lumbar plexus block versus femoral nerve block for analgesia and motor recovery after total knee arthroplasty
  9. Correlation between ABCB1 and OLIG2 polymorphisms and the severity and prognosis of patients with cerebral infarction
  10. Study on the radiotherapy effect and serum neutral granulocyte lymphocyte ratio and inflammatory factor expression of nasopharyngeal carcinoma
  11. Transcriptome analysis of effects of Tecrl deficiency on cardiometabolic and calcium regulation in cardiac tissue
  12. Aflatoxin B1 induces infertility, fetal deformities, and potential therapies
  13. Serum levels of HMW adiponectin and its receptors are associated with cytokine levels and clinical characteristics in chronic obstructive pulmonary disease
  14. METTL3-mediated methylation of CYP2C19 mRNA may aggravate clopidogrel resistance in ischemic stroke patients
  15. Understand how machine learning impact lung cancer research from 2010 to 2021: A bibliometric analysis
  16. Pressure ulcers in German hospitals: Analysis of reimbursement and length of stay
  17. Metformin plus L-carnitine enhances brown/beige adipose tissue activity via Nrf2/HO-1 signaling to reduce lipid accumulation and inflammation in murine obesity
  18. Downregulation of carbonic anhydrase IX expression in mouse xenograft nasopharyngeal carcinoma model via doxorubicin nanobubble combined with ultrasound
  19. Feasibility of 3-dimensional printed models in simulated training and teaching of transcatheter aortic valve replacement
  20. miR-335-3p improves type II diabetes mellitus by IGF-1 regulating macrophage polarization
  21. The analyses of human MCPH1 DNA repair machinery and genetic variations
  22. Activation of Piezo1 increases the sensitivity of breast cancer to hyperthermia therapy
  23. Comprehensive analysis based on the disulfidptosis-related genes identifies hub genes and immune infiltration for pancreatic adenocarcinoma
  24. Changes of serum CA125 and PGE2 before and after high-intensity focused ultrasound combined with GnRH-a in treatment of patients with adenomyosis
  25. The clinical value of the hepatic venous pressure gradient in patients undergoing hepatic resection for hepatocellular carcinoma with or without liver cirrhosis
  26. Development and validation of a novel model to predict pulmonary embolism in cardiology suspected patients: A 10-year retrospective analysis
  27. Downregulation of lncRNA XLOC_032768 in diabetic patients predicts the occurrence of diabetic nephropathy
  28. Circ_0051428 targeting miR-885-3p/MMP2 axis enhances the malignancy of cervical cancer
  29. Effectiveness of ginkgo diterpene lactone meglumine on cognitive function in patients with acute ischemic stroke
  30. The construction of a novel prognostic prediction model for glioma based on GWAS-identified prognostic-related risk loci
  31. Evaluating the impact of childhood BMI on the risk of coronavirus disease 2019: A Mendelian randomization study
  32. Lactate dehydrogenase to albumin ratio is associated with in-hospital mortality in patients with acute heart failure: Data from the MIMIC-III database
  33. CD36-mediated podocyte lipotoxicity promotes foot process effacement
  34. Efficacy of etonogestrel subcutaneous implants versus the levonorgestrel-releasing intrauterine system in the conservative treatment of adenomyosis
  35. FLRT2 mediates chondrogenesis of nasal septal cartilage and mandibular condyle cartilage
  36. Challenges in treating primary immune thrombocytopenia patients undergoing COVID-19 vaccination: A retrospective study
  37. Let-7 family regulates HaCaT cell proliferation and apoptosis via the ΔNp63/PI3K/AKT pathway
  38. Phospholipid transfer protein ameliorates sepsis-induced cardiac dysfunction through NLRP3 inflammasome inhibition
  39. Postoperative cognitive dysfunction in elderly patients with colorectal cancer: A randomized controlled study comparing goal-directed and conventional fluid therapy
  40. Long-pulsed ultrasound-mediated microbubble thrombolysis in a rat model of microvascular obstruction
  41. High SEC61A1 expression predicts poor outcome of acute myeloid leukemia
  42. Comparison of polymerase chain reaction and next-generation sequencing with conventional urine culture for the diagnosis of urinary tract infections: A meta-analysis
  43. Secreted frizzled-related protein 5 protects against renal fibrosis by inhibiting Wnt/β-catenin pathway
  44. Pan-cancer and single-cell analysis of actin cytoskeleton genes related to disulfidptosis
  45. Overexpression of miR-532-5p restrains oxidative stress response of chondrocytes in nontraumatic osteonecrosis of the femoral head by inhibiting ABL1
  46. Autologous liver transplantation for unresectable hepatobiliary malignancies in enhanced recovery after surgery model
  47. Clinical analysis of incomplete rupture of the uterus secondary to previous cesarean section
  48. Abnormal sleep duration is associated with sarcopenia in older Chinese people: A large retrospective cross-sectional study
  49. No genetic causality between obesity and benign paroxysmal vertigo: A two-sample Mendelian randomization study
  50. Identification and validation of autophagy-related genes in SSc
  51. Long non-coding RNA SRA1 suppresses radiotherapy resistance in esophageal squamous cell carcinoma by modulating glycolytic reprogramming
  52. Evaluation of quality of life in patients with schizophrenia: An inpatient social welfare institution-based cross-sectional study
  53. The possible role of oxidative stress marker glutathione in the assessment of cognitive impairment in multiple sclerosis
  54. Compilation of a self-management assessment scale for postoperative patients with aortic dissection
  55. Left atrial appendage closure in conjunction with radiofrequency ablation: Effects on left atrial functioning in patients with paroxysmal atrial fibrillation
  56. Effect of anterior femoral cortical notch grade on postoperative function and complications during TKA surgery: A multicenter, retrospective study
  57. Clinical characteristics and assessment of risk factors in patients with influenza A-induced severe pneumonia after the prevalence of SARS-CoV-2
  58. Analgesia nociception index is an indicator of laparoscopic trocar insertion-induced transient nociceptive stimuli
  59. High STAT4 expression correlates with poor prognosis in acute myeloid leukemia and facilitates disease progression by upregulating VEGFA expression
  60. Factors influencing cardiovascular system-related post-COVID-19 sequelae: A single-center cohort study
  61. HOXD10 regulates intestinal permeability and inhibits inflammation of dextran sulfate sodium-induced ulcerative colitis through the inactivation of the Rho/ROCK/MMPs axis
  62. Mesenchymal stem cell-derived exosomal miR-26a induces ferroptosis, suppresses hepatic stellate cell activation, and ameliorates liver fibrosis by modulating SLC7A11
  63. Endovascular thrombectomy versus intravenous thrombolysis for primary distal, medium vessel occlusion in acute ischemic stroke
  64. ANO6 (TMEM16F) inhibits gastrointestinal stromal tumor growth and induces ferroptosis
  65. Prognostic value of EIF5A2 in solid tumors: A meta-analysis and bioinformatics analysis
  66. The role of enhanced expression of Cx43 in patients with ulcerative colitis
  67. Choosing a COVID-19 vaccination site might be driven by anxiety and body vigilance
  68. Role of ICAM-1 in triple-negative breast cancer
  69. Cost-effectiveness of ambroxol in the treatment of Gaucher disease type 2
  70. HLA-DRB5 promotes immune thrombocytopenia via activating CD8+ T cells
  71. Efficacy and factors of myofascial release therapy combined with electrical and magnetic stimulation in the treatment of chronic pelvic pain syndrome
  72. Efficacy of tacrolimus monotherapy in primary membranous nephropathy
  73. Mechanisms of Tripterygium wilfordii Hook F on treating rheumatoid arthritis explored by network pharmacology analysis and molecular docking
  74. FBXO45 levels regulated ferroptosis renal tubular epithelial cells in a model of diabetic nephropathy by PLK1
  75. Optimizing anesthesia strategies to NSCLC patients in VATS procedures: Insights from drug requirements and patient recovery patterns
  76. Alpha-lipoic acid upregulates the PPARγ/NRF2/GPX4 signal pathway to inhibit ferroptosis in the pathogenesis of unexplained recurrent pregnancy loss
  77. Correlation between fat-soluble vitamin levels and inflammatory factors in paediatric community-acquired pneumonia: A prospective study
  78. CD1d affects the proliferation, migration, and apoptosis of human papillary thyroid carcinoma TPC-1 cells via regulating MAPK/NF-κB signaling pathway
  79. miR-let-7a inhibits sympathetic nerve remodeling after myocardial infarction by downregulating the expression of nerve growth factor
  80. Immune response analysis of solid organ transplantation recipients inoculated with inactivated COVID-19 vaccine: A retrospective analysis
  81. The H2Valdien derivatives regulate the epithelial–mesenchymal transition of hepatoma carcinoma cells through the Hedgehog signaling pathway
  82. Clinical efficacy of dexamethasone combined with isoniazid in the treatment of tuberculous meningitis and its effect on peripheral blood T cell subsets
  83. Comparison of short-segment and long-segment fixation in treatment of degenerative scoliosis and analysis of factors associated with adjacent spondylolisthesis
  84. Lycopene inhibits pyroptosis of endothelial progenitor cells induced by ox-LDL through the AMPK/mTOR/NLRP3 pathway
  85. Methylation regulation for FUNDC1 stability in childhood leukemia was up-regulated and facilitates metastasis and reduces ferroptosis of leukemia through mitochondrial damage by FBXL2
  86. Correlation of single-fiber electromyography studies and functional status in patients with amyotrophic lateral sclerosis
  87. Risk factors of postoperative airway obstruction complications in children with oral floor mass
  88. Expression levels and clinical significance of serum miR-19a/CCL20 in patients with acute cerebral infarction
  89. Physical activity and mental health trends in Korean adolescents: Analyzing the impact of the COVID-19 pandemic from 2018 to 2022
  90. Evaluating anemia in HIV-infected patients using chest CT
  91. Ponticulus posticus and skeletal malocclusion: A pilot study in a Southern Italian pre-orthodontic court
  92. Causal association of circulating immune cells and lymphoma: A Mendelian randomization study
  93. Assessment of the renal function and fibrosis indexes of conventional western medicine with Chinese medicine for dredging collaterals on treating renal fibrosis: A systematic review and meta-analysis
  94. Comprehensive landscape of integrator complex subunits and their association with prognosis and tumor microenvironment in gastric cancer
  95. New target-HMGCR inhibitors for the treatment of primary sclerosing cholangitis: A drug Mendelian randomization study
  96. Population pharmacokinetics of meropenem in critically ill patients
  97. Comparison of the ability of newly inflammatory markers to predict complicated appendicitis
  98. Comparative morphology of the cruciate ligaments: A radiological study
  99. Immune landscape of hepatocellular carcinoma: The central role of TP53-inducible glycolysis and apoptosis regulator
  100. Serum SIRT3 levels in epilepsy patients and its association with clinical outcomes and severity: A prospective observational study
  101. SHP-1 mediates cigarette smoke extract-induced epithelial–mesenchymal transformation and inflammation in 16HBE cells
  102. Acute hyper-hypoxia accelerates the development of depression in mice via the IL-6/PGC1α/MFN2 signaling pathway
  103. The GJB3 correlates with the prognosis, immune cell infiltration, and therapeutic responses in lung adenocarcinoma
  104. Physical fitness and blood parameters outcomes of breast cancer survivor in a low-intensity circuit resistance exercise program
  105. Exploring anesthetic-induced gene expression changes and immune cell dynamics in atrial tissue post-coronary artery bypass graft surgery
  106. Empagliflozin improves aortic injury in obese mice by regulating fatty acid metabolism
  107. Analysis of the risk factors of the radiation-induced encephalopathy in nasopharyngeal carcinoma: A retrospective cohort study
  108. Reproductive outcomes in women with BRCA 1/2 germline mutations: A retrospective observational study and literature review
  109. Evaluation of upper airway ultrasonographic measurements in predicting difficult intubation: A cross-section of the Turkish population
  110. Prognostic and diagnostic value of circulating IGFBP2 in pancreatic cancer
  111. Postural stability after operative reconstruction of the AFTL in chronic ankle instability comparing three different surgical techniques
  112. Research trends related to emergence agitation in the post-anaesthesia care unit from 2001 to 2023: A bibliometric analysis
  113. Frequency and clinicopathological correlation of gastrointestinal polyps: A six-year single center experience
  114. ACSL4 mediates inflammatory bowel disease and contributes to LPS-induced intestinal epithelial cell dysfunction by activating ferroptosis and inflammation
  115. Affibody-based molecular probe 99mTc-(HE)3ZHER2:V2 for non-invasive HER2 detection in ovarian and breast cancer xenografts
  116. Effectiveness of nutritional support for clinical outcomes in gastric cancer patients: A meta-analysis of randomized controlled trials
  117. The relationship between IFN-γ, IL-10, IL-6 cytokines, and severity of the condition with serum zinc and Fe in children infected with Mycoplasma pneumoniae
  118. Paraquat disrupts the blood–brain barrier by increasing IL-6 expression and oxidative stress through the activation of PI3K/AKT signaling pathway
  119. Sleep quality associate with the increased prevalence of cognitive impairment in coronary artery disease patients: A retrospective case–control study
  120. Dioscin protects against chronic prostatitis through the TLR4/NF-κB pathway
  121. Association of polymorphisms in FBN1, MYH11, and TGF-β signaling-related genes with susceptibility of sporadic thoracic aortic aneurysm and dissection in the Zhejiang Han population
  122. Application value of multi-parameter magnetic resonance image-transrectal ultrasound cognitive fusion in prostate biopsy
  123. Laboratory variables‐based artificial neural network models for predicting fatty liver disease: A retrospective study
  124. Decreased BIRC5-206 promotes epithelial–mesenchymal transition in nasopharyngeal carcinoma through sponging miR-145-5p
  125. Sepsis induces the cardiomyocyte apoptosis and cardiac dysfunction through activation of YAP1/Serpine1/caspase-3 pathway
  126. Assessment of iron metabolism and iron deficiency in incident patients on incident continuous ambulatory peritoneal dialysis
  127. Tibial periosteum flap combined with autologous bone grafting in the treatment of Gustilo-IIIB/IIIC open tibial fractures
  128. The application of intravenous general anesthesia under nasopharyngeal airway assisted ventilation undergoing ureteroscopic holmium laser lithotripsy: A prospective, single-center, controlled trial
  129. Long intergenic noncoding RNA for IGF2BP2 stability suppresses gastric cancer cell apoptosis by inhibiting the maturation of microRNA-34a
  130. Role of FOXM1 and AURKB in regulating keratinocyte function in psoriasis
  131. Parental control attitudes over their pre-school children’s diet
  132. The role of auto-HSCT in extranodal natural killer/T cell lymphoma
  133. Significance of negative cervical cytology and positive HPV in the diagnosis of cervical lesions by colposcopy
  134. Echinacoside inhibits PASMCs calcium overload to prevent hypoxic pulmonary artery remodeling by regulating TRPC1/4/6 and calmodulin
  135. ADAR1 plays a protective role in proximal tubular cells under high glucose conditions by attenuating the PI3K/AKT/mTOR signaling pathway
  136. The risk of cancer among insulin glargine users in Lithuania: A retrospective population-based study
  137. The unusual location of primary hydatid cyst: A case series study
  138. Intraoperative changes in electrophysiological monitoring can be used to predict clinical outcomes in patients with spinal cavernous malformation
  139. Obesity and risk of placenta accreta spectrum: A meta-analysis
  140. Shikonin alleviates asthma phenotypes in mice via an airway epithelial STAT3-dependent mechanism
  141. NSUN6 and HTR7 disturbed the stability of carotid atherosclerotic plaques by regulating the immune responses of macrophages
  142. The effect of COVID-19 lockdown on admission rates in Maternity Hospital
  143. Temporal muscle thickness is not a prognostic predictor in patients with high-grade glioma, an experience at two centers in China
  144. Luteolin alleviates cerebral ischemia/reperfusion injury by regulating cell pyroptosis
  145. Therapeutic role of respiratory exercise in patients with tuberculous pleurisy
  146. Effects of CFTR-ENaC on spinal cord edema after spinal cord injury
  147. Irisin-regulated lncRNAs and their potential regulatory functions in chondrogenic differentiation of human mesenchymal stem cells
  148. DMD mutations in pediatric patients with phenotypes of Duchenne/Becker muscular dystrophy
  149. Combination of C-reactive protein and fibrinogen-to-albumin ratio as a novel predictor of all-cause mortality in heart failure patients
  150. Significant role and the underly mechanism of cullin-1 in chronic obstructive pulmonary disease
  151. Ferroptosis-related prognostic model of mantle cell lymphoma
  152. Observation of choking reaction and other related indexes in elderly painless fiberoptic bronchoscopy with transnasal high-flow humidification oxygen therapy
  153. A bibliometric analysis of Prader-Willi syndrome from 2002 to 2022
  154. The causal effects of childhood sunburn occasions on melanoma: A univariable and multivariable Mendelian randomization study
  155. Oxidative stress regulates glycogen synthase kinase-3 in lymphocytes of diabetes mellitus patients complicated with cerebral infarction
  156. Role of COX6C and NDUFB3 in septic shock and stroke
  157. Trends in disease burden of type 2 diabetes, stroke, and hypertensive heart disease attributable to high BMI in China: 1990–2019
  158. Purinergic P2X7 receptor mediates hyperoxia-induced injury in pulmonary microvascular endothelial cells via NLRP3-mediated pyroptotic pathway
  159. Investigating the role of oviductal mucosa–endometrial co-culture in modulating factors relevant to embryo implantation
  160. Analgesic effect of external oblique intercostal block in laparoscopic cholecystectomy: A retrospective study
  161. Elevated serum miR-142-5p correlates with ischemic lesions and both NSE and S100β in ischemic stroke patients
  162. Correlation between the mechanism of arteriopathy in IgA nephropathy and blood stasis syndrome: A cohort study
  163. Risk factors for progressive kyphosis after percutaneous kyphoplasty in osteoporotic vertebral compression fracture
  164. Predictive role of neuron-specific enolase and S100-β in early neurological deterioration and unfavorable prognosis in patients with ischemic stroke
  165. The potential risk factors of postoperative cognitive dysfunction for endovascular therapy in acute ischemic stroke with general anesthesia
  166. Fluoxetine inhibited RANKL-induced osteoclastic differentiation in vitro
  167. Detection of serum FOXM1 and IGF2 in patients with ARDS and their correlation with disease and prognosis
  168. Rhein promotes skin wound healing by activating the PI3K/AKT signaling pathway
  169. Differences in mortality risk by levels of physical activity among persons with disabilities in South Korea
  170. Review Articles
  171. Cutaneous signs of selected cardiovascular disorders: A narrative review
  172. XRCC1 and hOGG1 polymorphisms and endometrial carcinoma: A meta-analysis
  173. A narrative review on adverse drug reactions of COVID-19 treatments on the kidney
  174. Emerging role and function of SPDL1 in human health and diseases
  175. Adverse reactions of piperacillin: A literature review of case reports
  176. Molecular mechanism and intervention measures of microvascular complications in diabetes
  177. Regulation of mesenchymal stem cell differentiation by autophagy
  178. Molecular landscape of borderline ovarian tumours: A systematic review
  179. Advances in synthetic lethality modalities for glioblastoma multiforme
  180. Investigating hormesis, aging, and neurodegeneration: From bench to clinics
  181. Frankincense: A neuronutrient to approach Parkinson’s disease treatment
  182. Sox9: A potential regulator of cancer stem cells in osteosarcoma
  183. Early detection of cardiovascular risk markers through non-invasive ultrasound methodologies in periodontitis patients
  184. Advanced neuroimaging and criminal interrogation in lie detection
  185. Maternal factors for neural tube defects in offspring: An umbrella review
  186. The chemoprotective hormetic effects of rosmarinic acid
  187. CBD’s potential impact on Parkinson’s disease: An updated overview
  188. Progress in cytokine research for ARDS: A comprehensive review
  189. Utilizing reactive oxygen species-scavenging nanoparticles for targeting oxidative stress in the treatment of ischemic stroke: A review
  190. NRXN1-related disorders, attempt to better define clinical assessment
  191. Lidocaine infusion for the treatment of complex regional pain syndrome: Case series and literature review
  192. Trends and future directions of autophagy in osteosarcoma: A bibliometric analysis
  193. Iron in ventricular remodeling and aneurysms post-myocardial infarction
  194. Case Reports
  195. Sirolimus potentiated angioedema: A case report and review of the literature
  196. Identification of mixed anaerobic infections after inguinal hernia repair based on metagenomic next-generation sequencing: A case report
  197. Successful treatment with bortezomib in combination with dexamethasone in a middle-aged male with idiopathic multicentric Castleman’s disease: A case report
  198. Complete heart block associated with hepatitis A infection in a female child with fatal outcome
  199. Elevation of D-dimer in eosinophilic gastrointestinal diseases in the absence of venous thrombosis: A case series and literature review
  200. Four years of natural progressive course: A rare case report of juvenile Xp11.2 translocations renal cell carcinoma with TFE3 gene fusion
  201. Advancing prenatal diagnosis: Echocardiographic detection of Scimitar syndrome in China – A case series
  202. Outcomes and complications of hemodialysis in patients with renal cancer following bilateral nephrectomy
  203. Anti-HMGCR myopathy mimicking facioscapulohumeral muscular dystrophy
  204. Recurrent opportunistic infections in a HIV-negative patient with combined C6 and NFKB1 mutations: A case report, pedigree analysis, and literature review
  205. Letter to the Editor
  206. Letter to the Editor: Total parenteral nutrition-induced Wernicke’s encephalopathy after oncologic gastrointestinal surgery
  207. Erratum
  208. Erratum to “Bladder-embedded ectopic intrauterine device with calculus”
  209. Retraction
  210. Retraction of “XRCC1 and hOGG1 polymorphisms and endometrial carcinoma: A meta-analysis”
  211. Corrigendum
  212. Corrigendum to “Investigating hormesis, aging, and neurodegeneration: From bench to clinics”
  213. Corrigendum to “Frankincense: A neuronutrient to approach Parkinson’s disease treatment”
  214. Special Issue The evolving saga of RNAs from bench to bedside - Part II
  215. Machine-learning-based prediction of a diagnostic model using autophagy-related genes based on RNA sequencing for patients with papillary thyroid carcinoma
  216. Unlocking the future of hepatocellular carcinoma treatment: A comprehensive analysis of disulfidptosis-related lncRNAs for prognosis and drug screening
  217. Elevated mRNA level indicates FSIP1 promotes EMT and gastric cancer progression by regulating fibroblasts in tumor microenvironment
  218. Special Issue Advancements in oncology: bridging clinical and experimental research - Part I
  219. Ultrasound-guided transperineal vs transrectal prostate biopsy: A meta-analysis of diagnostic accuracy and complication rates
  220. Assessment of diagnostic value of unilateral systematic biopsy combined with targeted biopsy in detecting clinically significant prostate cancer
  221. SENP7 inhibits glioblastoma metastasis and invasion by dissociating SUMO2/3 binding to specific target proteins
  222. MARK1 suppress malignant progression of hepatocellular carcinoma and improves sorafenib resistance through negatively regulating POTEE
  223. Analysis of postoperative complications in bladder cancer patients
  224. Carboplatin combined with arsenic trioxide versus carboplatin combined with docetaxel treatment for LACC: A randomized, open-label, phase II clinical study
  225. Special Issue Exploring the biological mechanism of human diseases based on MultiOmics Technology - Part I
  226. Comprehensive pan-cancer investigation of carnosine dipeptidase 1 and its prospective prognostic significance in hepatocellular carcinoma
  227. Identification of signatures associated with microsatellite instability and immune characteristics to predict the prognostic risk of colon cancer
  228. Single-cell analysis identified key macrophage subpopulations associated with atherosclerosis
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