Home Medicine OKAIN: A comprehensive oncology knowledge base for the interpretation of clinically actionable alterations
Article Open Access

OKAIN: A comprehensive oncology knowledge base for the interpretation of clinically actionable alterations

  • Zhenhua Yang , Chunwei Xu , Mingmin Wang , Xinxiu Meng , Kai Wang and Aodi Wang EMAIL logo
Published/Copyright: October 30, 2025
Download Article (PDF)
Open Medicine
From the journal Open Medicine Volume 20 Issue 1

Abstract

The increased use of next-generation sequencing in clinical genetic testing has resulted in the identification of several genetic variations with possible therapeutic implications. We developed OKAIN (https://szcube.origimed.com), an algorithm tool that assesses clinically actionable mutations using a precision oncology knowledge database. OKAIN employs a weighted evidence analysis system to deliver final clinical annotation outcomes for intricate variations. As of now, OKAIN has amassed over 100,000 variants in 1,239 cancer-associated genes, encompassing 12,409 entries of therapeutic evidence in 471 genes. This collection highlights 2,600 Level A evidence entries in 66 genes, with 864 entries derived from the National Medical Products Administration labels or Chinese guidelines. OKAIN acts as a precision oncology knowledge base for the assessment of clinically actionable alterations, integrating exhaustive data related to cancer-associated genomic variants and therapeutic efficacy. Analyzing patient variants with OKAIN reveals more actionable targeted therapy or immunotherapy options, potentially improving treatment outcomes.

Keywords: precision oncology; tumor knowledge base; genomic alterations; classification system; weighted evidence analysis

1 Introduction

Precision oncology is a rapidly emerging field that involves the molecular profiling of tumors to discern diagnostic, prognostic, and therapeutic implications [1–3]. Patients are increasingly undergoing multigene sequencing of individual tumors to identify potential tumor biomarkers that could be effectively targeted with corresponding drugs. Both the Food and Drug Administration (FDA) and the National Medical Products Administration (NMPA) have approved numerous drugs based on these biomarkers, such as larotrectinib. For example, larotrectinib can be successfully used as a treatment when an NTRK fusion is identified in a solid tumor patient without a known acquired resistance mutation.

While there is a broad consensus on the interpretation of certain genomic alterations, such as epidermal growth factor receptor (EGFR) T790M and EGFR L858R, a large number of genetic variants that lack consensus for interpretation pose a significant challenge [4–6], including co-mutations and acquired drug-resistance variants. The use of precision medical technology in oncology has led to the widespread adoption of next-generation sequencing (NGS) large panel detection as the primary clinical approach. This method allows for comprehensive coverage of rare mutation targets, systematic identification of co-occurring mutations in tumors, and significant improvements in clinical detection efficiency. However, accurately interpreting rare mutations remains a major clinical challenge. Therefore, it is necessary to create a precision oncology knowledge base that offers centralized, freely accessible, and accurately interpreted clinical information on genomic data. This tool would assist clinicians in interpreting genomic alterations detected in patient tumor samples, enabling them to make optimal treatment decisions.

Existing knowledge bases designed to aid in the clinical interpretation of alterations include resources such as Clinical Interpretation of Variants in Cancer (CIViC) [4] and OncoKB [5]. However, most of these databases provide either the final clinical annotation results or multiple pieces of clinical interpretation evidence for the alterations. Additionally, thorough annotations of gene variations of Chinese drugs are not considered in most of those databases.

To address this issue, we present OKAIN, a knowledge base for precision oncology that assesses clinically actionable alterations. OKAIN includes a wide range of information related to genomic variants associated with cancer and their effectiveness in treatment. Its purpose is to offer physicians precise and structured interpretations of cancer mutations found in patients’ tumors, thereby facilitating clinical decision making.

OKAIN provides comprehensive insights into the therapeutic efficacy of co-mutations, acquired drug-resistant variants, and rare mutations, assisting physicians in precisely treating patients with complex variants. The knowledge base includes a weighted evidence analysis system that conducts a thorough analysis of the evidence related to the therapeutic efficacy of a tumor patient’s cancer-associated genomic variants. This system enables the acquisition of robust evidence of therapeutic efficacy in tumor patients.

2 Methods

OKAIN (Version 1.0, 2024) accommodates clinically relevant cancer variants, including single nucleotide variants, frameshifts, insertions, deletions, gene rearrangements, copy number variations, and changes in expression levels. These variants are described unambiguously using the HGVS nomenclature [7,8]. OKAIN contains information about the biological effects and treatment implications of specific cancer genes and their variations. As shown in Figure 1, the data are sourced from a variety of authoritative entities, encompassing the FDA, NMPA, clinical guidelines, peer-reviewed scientific journals, and major conference proceedings, among others. Biological and clinical implications are meticulously reviewed by oncologist teams. To ensure a clear and precise representation of data, we will structure the information systematically. The structured data will include genes, variants, indication, drug, potency, source of evidence, level of evidence, and description of evidence. The weighted evidence analysis system to deliver final clinical annotation outcomes for intricate variations. The OKAIN dataset is mainly used for clinical research and to enhance OrigiMed’s clinical reporting. Users can access this dataset through an intuitive and interactive web interface at https://szcube.origimed.com.

Figure 1 OKAIN workflow.
Figure 1

OKAIN workflow.

In accordance with guidelines from the American Society of Clinical Oncology, the Association for Molecular Pathology, the College of American Pathologists, and the European Society for Medical Oncology [9,10], as well as information from public databases like OncoKB and consensus among oncologists, we have developed levels of evidence classification system (Table 1).

Table 1

Levels of evidence classification system

Potency Category Therapeutic
Response Level A A biomarker predictive of response to FDA/NMPA-approved therapies or those recommended by clinical guidelines in this indication
Level B A biomarker predictive of response to therapies, demonstrated by extensive retrospective studies or prospective investigations (Phase III clinical studies), in this indication
Level C C1. A biomarker predictive of response to FDA/NMPA-approved therapies or those recommended by clinical guidelines in another indication
C2. A biomarker predictive of response to therapies, demonstrated by small-scale retrospective studies or early-stage prospective studies (Phase I or II clinical studies) in this indication
Level D D1. A biomarker predictive of response to therapies, demonstrated by a limited number of case reports in this indication
D2. A biomarker predictive of response to therapies, supported by preclinical study results
Resistance Level R1 A biomarker predictive of resistance to therapies, authorized by the FDA/NMPA or advised in professional clinical guidelines in this indication
Level R2 R2B. A biomarker predictive of resistance to therapies, demonstrated by extensive retrospective studies or prospective investigations (Phase III clinical studies), in this indication
R2C. A biomarker predictive of resistance to therapies, demonstrated by small-scale retrospective studies or early-stage prospective studies (Phase I or II clinical studies) in this indication
R2D1. A biomarker predictive of resistance to therapies, demonstrated by a limited number of case reports in this indication
R2D2. A biomarker predictive of resistance to therapies, supported by preclinical study results

Continual research on the efficacy of genomic variants often produces conflicting evidence regarding the effectiveness of specific gene alterations. This poses a significant obstacle to the rapid interpretation of genomic alterations. To address this issue, OKAIN’s weighted evidence analysis system performs a comprehensive analysis of all therapeutic efficacy evidence for a specific genomic variant related to a particular drug, to determine the highest degree of efficacy for that drug. The highest level of efficacy is then evaluated against all variants of the gene, resulting in efficacy data for all gene variants in relation to the medication (Figure 2).

Figure 2 OKAIN’s weighted evidence analysis system. The Highest Efficacy Level indicates the maximal therapeutic effect for the specific genomic variant in response to a specific drug.
Figure 2

OKAIN’s weighted evidence analysis system. The Highest Efficacy Level indicates the maximal therapeutic effect for the specific genomic variant in response to a specific drug.

Within this framework, sensitivity evidence levels (A, B, C, D) exhibit direct correspondence with resistance evidence levels (R1, R2B, R2C, R2D), respectively, when weighted for a specific gene–tumor–drug–variant association. Sensitivity evidence levels follow a hierarchical order from highest to lowest (A → B → C → D), while resistance evidence levels descend correspondingly (R1 → R2B → R2C → R2D).

OKAIN prioritizes negative clinical evidence, discouraging the use of targeted therapies when the evidence suggests the therapy may be ineffective or controversial. When weighing the evidence level for multiple variants based on a specific drug, the evidence for drug resistance and conflicting evidence is prioritized over the level of evidence for sensitivity.

The Highest Efficacy Level represents the most clinically significant evidence tier for a specific gene–tumor–drug–variant, encompassing both sensitivity and resistance classifications following weighting analysis. For example, a variant may concurrently exhibit Level A, Level C, Level D, Level R2B, and Level R2D, wherein the Highest Efficacy Level would report Level A (highest sensitivity) and Level R2B (highest resistance).

The First Weighted Level denotes the definitive therapeutic efficacy prediction for a specific genomic variant in a given tumor type, derived directly from the Highest Efficacy Level. When conflicting evidence exists (e.g., concurrent sensitivity and resistance classifications), the system outputs “Conflict.”

The Second Weighted Level denotes the consensus therapeutic efficacy for all variants of a gene within a specified drug–tumor context, derived through aggregation of First Weighted Levels. This tier exclusively retains the highest efficacy level (sensitivity or resistance) observed across variants. When multiple distinct sensitivity types coexist within the definitive First Weighted Levels, prioritization follows the hierarchy: Resistance → Conflict → Response, preserving only the highest-priority classification. Should the Second Weighted Level manifest as “Conflict,” the final display will default to “Resistance” paired with the Highest Resistance Level, thereby prioritizing patient safety through avoidance of contentious therapeutic approaches.

3 Results

3.1 Levels of evidence

OKAIN categorizes the evidence for sensitivity to targeted therapies into four levels (A, B, C, and D) for each genetic alteration, based on the strength of clinical and preclinical data supporting the use of the mutation as a predictive biomarker.

Level A includes specific alterations that have been approved by the FDA/NMPA or recommended by clinical professional guidelines as predictive of response to particular therapies in specific tumors. The FDA has approved avapritinib as a treatment for adult patients with unresectable or metastatic gastrointestinal stromal tumor (GIST) that harbor a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including PDGFRA D842V mutations. Avapritinib is a tyrosine kinase inhibitor that targets PDGFRA and PDGFRA D842 mutants, as well as multiple KIT proto-oncogene (KIT) exon 11, 11/17, and 17 mutations with half-maximal inhibitory concentrations (IC50s) less than 25 nM. In vitro cellular assays, avapritinib inhibited the autophosphorylation of KIT D816V and PDGFRA D842V mutants, which are associated with resistance to approved kinase inhibitors. The IC50 for KIT D816V was 4 nM and for PDGFRA D842V was 30 nM. Therefore, the use of avapritinib to treat GIST patients with PDGFRA D842V mutations is classified as Level A (Figure 3).

Figure 3 Examples of the OKAIN levels of evidence. The level of evidence shows the efficacy for a specific genomic variant related to a particular drug.
Figure 3

Examples of the OKAIN levels of evidence. The level of evidence shows the efficacy for a specific genomic variant related to a particular drug.

Level B includes specific alterations that serve as predictive biomarkers of response to therapies. These alterations have been established through large-scale retrospective studies or prospective studies, at least Phase III, in particular types of tumors. The ZETA Trial, a Phase III study, showed that patients with medullary thyroid cancer (MTC) who had a somatic RET M918T mutation had a higher objective response rate to vandetanib (55%) than patients with sporadic MTC tumors that lacked a somatic M918T mutation (33%) [11]. In vitro studies have shown that vandetanib inhibits the tyrosine kinase activity of various receptor tyrosine kinases, including the EGFR and vascular endothelial growth factor (VEGFR) families, Ret proto-oncogene (RET), protein tyrosine kinase 6 (BRK), TEK receptor tyrosine kinase (TIE2), and members of the EPH receptor and Src kinase families. These kinases play a role in both normal cellular functions and pathological processes such as oncogenesis, metastasis, tumor angiogenesis, and maintenance of the tumor microenvironment. The RET M918T mutation in MTC is classified as Level B based on emerging Phase III clinical data (Figure 3).

Level C is divided into two sub-levels: C1 and C2. Level C1 includes alterations that have received FDA/NMPA approval or are recommended by clinical professional guidelines as predictive of response to therapies in different types of tumors. For example, anaplastic lymphoma kinase (ALK) rearrangements are found in 2–7% of non-small-cell lung cancer (NSCLC) patients [12,13]. The FDA has approved several ALK TKIs, including crizotinib, alectinib, ceritinib, brigatinib, and lorlatinib, for treating ALK-positive NSCLC. Studies have also shown that ALK TKIs produce significant clinical responses in ALK-positive non-NSCLC patients [14–21]. The available evidence indicates that targeted therapy may be beneficial for these patients. As a result, ALK rearrangement is classified as Level C1 in non-NSCLC tumors, based on evidence derived from NSCLC. Level C2 includes alterations that predict biomarkers of response to therapies, as established by small retrospective or prospective studies (Phase I or II) in specific types of tumors. Phosphatase and tensin homolog (PTEN) is often deregulated in advanced prostate cancers, leading to the activation of the PI3K-Akt-mTOR pathway and increased cell survival. A Phase II study (NCT00976755) of everolimus, an mTOR inhibitor, was conducted in patients with metastatic castration-resistant prostate cancer. The study found that PTEN deletion was associated with higher disease remission rates and improved progression-free survival (PFS) [22]. According to the emerging Phase II clinical data, PTEN deletion is classified as a Level C2 mutation in prostate cancer (Figure 3).

Level D is subdivided into Levels D1 and D2. These levels include alterations that are candidate predictive biomarkers of response to therapies based solely on a few reported cases in specific tumors (Level D1) or preclinical studies (Level D2). Futibatinib is a potent inhibitor that targets the FGFR family. It has high affinity for FGFR 1, 2, 3, and 4, with IC50 values below 4 nM. Futibatinib forms a covalent bond with FGFR, effectively inhibiting FGFR phosphorylation, disrupting downstream signaling pathways, and reducing the viability of cancer cells harboring FGFR alterations, including fusions/rearrangements, amplifications, and mutations. Clinical observations have shown that patients with gastric cancer featuring FGFR2 amplification respond to futibatinib treatment [23,24]. Consequently, in the context of gastric cancer, FGFR2 amplification has been classified as a Level D1 mutation (Figure 3).

OKAIN classifies evidence for resistance into two main levels: R1 and R2. Level R1 includes alterations that have been approved by the FDA/NMPA or recommended by clinical professional guidelines as predictive of resistance to therapies in specific tumors. An example of this is the PDGFRA D842V mutation, which has been shown to cause resistance to imatinib in patients with GISTs (Figure 3). Resistance evidence Level R2 is subdivided into R2B, R2C, and R2D, which correspond to sensitivity evidence levels B, C, and D, respectively. This stratification facilitates the precise weighting of clinical evidence.

3.2 Examples of weighted analysis interpretation

OKAIN logs all clinical data for each genomic alteration, enabling physicians to comprehensively review the therapeutic implications. A single genetic variant may correspond to multiple efficacy levels for a given therapeutic strategy (Figure 4). The evidence analysis system is designed to help physicians obtain conclusive evidence of therapeutic efficacy for cancer patients quickly and succinctly.

Figure 4 Examples of OKAIN weighted analysis interpretation. The level of evidence shows the efficacy for the specific genomic variant related to a particular drug. The Highest Efficacy Level indicates the maximal therapeutic effect for the specific genomic variant in response to a specific drug. The First Weighted Level indicates the ultimate drug efficacy for the specific genomic variant, as determined after applying a weighting analysis. If the Highest Efficacy Level presents conflicting evidence, the system will output “Conflict.” The Second Weighted Level specifies the definitive efficacy for all variants of the gene. If the highest level presents conflicting evidence, the system outputs “Conflict.” The display shows the ultimate efficacy for all variants of the gene related to the drug. “*” prompting that the sensitivity of ALK rearrangement and ALK G1269A co-mutation is controversial.
Figure 4

Examples of OKAIN weighted analysis interpretation. The level of evidence shows the efficacy for the specific genomic variant related to a particular drug. The Highest Efficacy Level indicates the maximal therapeutic effect for the specific genomic variant in response to a specific drug. The First Weighted Level indicates the ultimate drug efficacy for the specific genomic variant, as determined after applying a weighting analysis. If the Highest Efficacy Level presents conflicting evidence, the system will output “Conflict.” The Second Weighted Level specifies the definitive efficacy for all variants of the gene. If the highest level presents conflicting evidence, the system outputs “Conflict.” The display shows the ultimate efficacy for all variants of the gene related to the drug. “*” prompting that the sensitivity of ALK rearrangement and ALK G1269A co-mutation is controversial.

The FDA/NMPA has approved several ALK TKIs for treating NSCLC patients with ALK rearrangement. Crizotinib, ceritinib, ensartinib, alectinib, brigatinib, and lorlatinib are all designated as Level A for this rearrangement. Additionally, numerous preclinical studies have classified this rearrangement as Level D, predicting sensitivity to ALK TKIs [25–27]. The weighting system prioritizes the highest efficacy level for genomic alterations with multiple levels. Therefore, ALK rearrangement is categorized as Level A for crizotinib, ceritinib, ensartinib, alectinib, brigatinib, and lorlatinib. If conflicting evidence is present for the highest level, the system outputs “Conflict.” As shown in Figure 4, the ALK rearrangement and ALK G1269A co-mutation are classified as Level D and R2D for alectinib, according to various literature sources [28–31]. In this case, the system would output “Conflict” when weighted. OKAIN highlights resistant clinical evidence to ensure patients do not lose valuable treatment time due to potentially ineffective targeted drugs, even if the ALK rearrangement is classified as Level A for alectinib. The co-occurrence of ALK rearrangement and ALK G1269A mutation is ultimately categorized as “Level R2*”, with “*” indicating that the sensitivity of this co-mutation to alectinib is controversial. Similarly, ALK rearrangement and ALK G1269A co-mutations are ultimately classified as “Level R2*” [32,33]. When the highest level of evidence indicates resistance, the ALK rearrangement and ALK G1269A co-mutations are ultimately classified as Level R2 for crizotinib and entrectinib [25,30,31].

3.3 Quantity of evidence in the OKAIN knowledge base

To date, OKAIN has amassed over 100,000 variants in 1,239 cancer-associated genes, encompassing 12,409 entries of therapeutic evidence in 471 genes. This collection highlights 2,600 Level A evidence entries in 66 genes, with 864 entries derived from either the NMPA label or Chinese guidelines (Table S1). The EGFR, erb-B2 receptor tyrosine kinase 2 (ERBB2/HER2), ALK, KIT, MET proto-oncogene (MET), and B-Raf proto-oncogene (BRAF) genes are associated with the largest numbers of therapeutic evidence (Figure 5a). Lung carcinoma is the largest proportion of therapeutic evidence by tumor type, due to its association with the largest number of therapeutic strategies (Figure 5b).

Figure 5 Distribution of therapeutic evidence. (a) Distribution of therapeutic evidence for genes in OKAIN knowledge base when ranked by the number of interpretations in the database. (b) Distribution of therapeutic evidence for different tumor types in OKAIN knowledge base when ranked by the number of interpretations in the clinical data.
Figure 5

Distribution of therapeutic evidence. (a) Distribution of therapeutic evidence for genes in OKAIN knowledge base when ranked by the number of interpretations in the database. (b) Distribution of therapeutic evidence for different tumor types in OKAIN knowledge base when ranked by the number of interpretations in the clinical data.

3.4 Clinically actionable variations in Chinese patients

To quantify the potential clinical impact of prospective broad tumor genomic testing, we annotated the variants in a publicly available dataset of 10,194 solid tumors with China Pan-cancer cohort (OrigiMed, Nature 2022) using the OKAIN knowledge base (Version 1.0, 2024) and the OncoKB (http://oncokb.org/, v4.13) knowledge base, respectively [34]. As shown in Figure 6, Tables S2 and S3, the proportions of OKAIN and OncoKB actionability were 74.1% of patients (N  =  7,555 harbored at least one gene variant with a variable highest level of clinical evidence, Level A, 34.7%; Level B, 0.8%; Level C, 20.5%; Level D, 18.2%) and 67.8% (N  =  6,911, Level 1, 34.5%; Level 2, 1.0%; Level 3, 19.4%; Level 4, 12.9%), respectively. Complete concordance in clinical actionability annotations was observed, with all 6,911 OncoKB-annotated actionable cases similarly classified as actionable by OAKIN. McNemar’s test was used to assess inter-system differences. Relative to OncoKB, the OKAIN knowledge base demonstrated significantly broader patient coverage (74.1 vs 67.8%; P < 0.001) for targeted or immunotherapeutic eligibility, reflecting its systematic evidence aggregation framework for genomic aberration-specific efficacy data.

Figure 6 Clinical actionability of somatic variants in the China Pan-cancer cohort. Variants were assigned to different levels of clinical actionability according to OKAIN knowledge base. (a) Distribution of the highest level of actionable variants across all patients. (b) Distribution of highest level of actionable variants across tumor types.
Figure 6

Clinical actionability of somatic variants in the China Pan-cancer cohort. Variants were assigned to different levels of clinical actionability according to OKAIN knowledge base. (a) Distribution of the highest level of actionable variants across all patients. (b) Distribution of highest level of actionable variants across tumor types.

Discrepancies between OncoKB and OKAIN in identifying patients for therapies and drug sensitivities to actionable variants are highlighted by differences in their clinical assessment and evidence integration (Tables S4, S5 and S6). These variations may stem from OKAIN’s inclusion of additional clinical factors, such as hormone receptor (HR) and HER2 status, in its assessment criteria. The FDA’s approval of capivasertib, in combination with fulvestrant for adult patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer with PIK3CA/AKT1/PTEN-alterations post-progression on endocrine therapy, underscores the significance of these factors. When a patient’s HR or HER2 status is either unknown or not HR-positive and HER2-negative, the evidence level assigned to capivasertib for treating breast cancer is adjusted to Level C. Additionally, it may stem from the inclusion of drugs approved in China and recommended by the Chinese Society of Clinical Oncology (CSCO) guidelines (https://www.csco.org.cn/) in OKAIN, which are not listed in OncoKB, such as almonertinib. Moreover, OKAIN’s consideration of a broader evidence base may explain these differences. For example, based on clinical trial data, patients with renal cell carcinoma who have Von Hippel-Lindau tumor suppressor (VHL) alterations may benefit from treatments like sunitinib, sorafenib, bevacizumab, or axitinib [35]. Concurrently, preclinical findings indicate that GISTs harboring the KIT A502_Y503dup mutation may be less responsive to imatinib therapy [36].

4 Discussion

The adoption of NGS in clinical genetic testing has become widespread, leading to the discovery of numerous genetic variants that may impact clinical decision-making. This highlights the significance and advantages of standardized interpretation of these variants [9]. There are several resources available to aid in the clinical interpretation of genetic alterations, such as CIViC [4], OncoKB [5], COSMIC [37], the JAX Clinical Knowledge base [38], the Cancer Driver Log [39], and the Precision Medicine Knowledge Base [40]. These databases offer either the final clinical annotation results or multiple pieces of clinical interpretation evidence related to the alterations. However, until now, there has been a lack of databases published specifically to interpret genetic variants in China. In this context, OKAIN emerges as the first precision oncology knowledge base published in China. This resource offers physicians detailed and structured interpretations of cancer mutations found in patient tumors, along with evidence of therapeutic efficacy through a weighted analysis system. Its potential to enhance precision oncology practice in China is significant.

Like other classification systems [5,9], OKAIN divides the sensitivity evidence into four levels for each mutation, based on the available clinical and preclinical data that support the use of the mutation as a predictive biomarker. The evidence sensitivity levels, ranked from highest to lowest, are A, B, C, and D. Therapeutic implications approved by FDA/NMPA or recommended by clinical professional guidelines for specific tumors are classified as level A. All other therapeutic implications are classified as levels B, C, and D, respectively. The significance of the latter lies in its potential to offer new therapeutic strategies for cancer patients, including off-label use of cancer drugs and enrollment in appropriate clinical trials. However, we do not recommend using cancer drugs off-label for different tumor types due to the limited evidence supporting their efficacy. It is important to consider the safety profile and accessibility of these medications as well as the variability in their effectiveness across different tumors. For example, the results of a phase II trial (NCT00903175) demonstrate the variability of patient outcomes when treated with everolimus for renal cell carcinoma. Patients who retained PTEN expression had a median PFS of 5.3 months, while those who lost PTEN expression experienced a significantly longer median PFS of 10.5 months (P < 0.001) [41]. This finding suggests that PTEN status may have predictive value in this context. In contrast, data from another study on transitional cell carcinoma suggest that PTEN loss may be associated with resistance to everolimus. This indicates that the efficacy of this drug is not consistent across different tumor types and that molecular profiles should be carefully considered before off-label application [42].

Although clinical and preclinical studies suggest that certain gene mutations may respond to specific targeted drugs, it is important to note that the gene may not actually be the target of the drug. Currently, there is insufficient research to explain this phenomenon adequately. For example, biomarker analyses of the BERIL-1 trial showed that patients with squamous cell carcinoma of the head and neck, who also had TP53 alterations, benefited from the combination of buparlisib and paclitaxel in terms of survival [43]. However, further investigation is required to establish a definitive link between TP53 alterations and improved outcomes with this drug combination. Therefore, although TP53 alterations are not currently considered agents in OKAIN, they are still recorded for reference.

OKAIN continuously records new clinical data, including updates to NMPA/FDA labels, professional guidelines, and scientific literature, ensuring that the weighted level of evidence remains current. For example, RET rearrangement was not considered as level A in thyroid cancer until December 1, 2020, when the FDA approved pralsetinib for the treatment of adult and pediatric patients (12 years of age and older) with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and are radioactive iodine-refractory. This timely inclusion of new clinical data enhances the utility of OKAIN for making informed therapeutic decisions.

OKAIN plans to conduct weighted analyses for complex variants, including multiple genetic variants, rather than solely focusing on single-gene alterations. Additionally, they aim to establish a platform where physicians can engage in discussions and provide comments on variant annotations, aiding in their accurate understanding of these alterations.

OKAIN has entered clinical practice across multiple settings, supporting critical oncology workflows including: (1) interpretation of NGS reports to deliver clinically actionable results, (2) genetic counseling sessions, and (3) Molecular Tumor Board discussions by providing evidence for therapeutic decision-making. Ongoing real-world studies are quantitatively assessing OKAIN’s implementation fidelity, impact on therapeutic recommendations, and broader utility in precision oncology pathways.

5 Conclusions

OKAIN is a knowledge base for cancer genomics and precision treatment, including therapies approved in China and those recommended by Chinese clinical guidelines. OKAIN presents an extensive array of evidence, enhanced by a specialized weighting system, facilitating precision treatment for clinicians and patients with complex variations. Analyzing patient variants with OKAIN reveals more actionable targeted therapy or immunotherapy options, potentially improving treatment outcomes.

# Zhenhua Yang and Chunwei Xu contributed equally to the study.

Acknowledgments

The authors appreciate the support of all participants for this study.

  1. Funding information: This work is supported by the China Postdoctoral Science Foundation (2022M723207), the Medical Scientific Research Foundation of Zhejiang Province of China (2023KY666), the Zhejiang Traditional Chinese Medicine Science Fund Project (2024ZL372), and the Qiantang Cross Fund Project (2023-16).

  2. Author contributions: Aodi Wang, Zhenhua Yang, Chunwei Xu, Mingmin Wang, and Xinxiu Meng collectively contributed to the conceptualization and design of the OKAIN knowledge base’s logical framework. They also played a pivotal role in supervising the ongoing updates and the rigorous review process of the knowledge content. Aodi Wang, Zhenhua Yang, and Chunwei Xu were instrumental in the data gathering and analytical efforts. Zhenhua Yang took the lead in composing the initial draft of the manuscript. Subsequently, Aodi Wang, Chunwei Xu, Xinxiu Meng, and Kai Wang joined Zhenhua Yang in meticulously reviewing and editing the text to ensure its coherence and scholarly integrity. Zhenhua Yang and Chunwei Xu are the first co-authors and contributed equally to the study. All authors have meticulously reviewed, provided input, and consented to the final version of the manuscript.

  3. Conflict of interest: The authors declare that they have no conflict of interest.

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

References

[1] Schwartzberg L, Kim ES, Liu D, Schrag D. Precision oncology: who, how, what, when, and when not? Am Soc Clin Oncol Educ Book. 2017;7:160–9.10.1200/EDBK_174176Search in Google Scholar

[2] Li X, Warner JL. A review of precision oncology knowledge bases for determining the clinical actionability of genetic variants. Front Cell Dev Biol. 2020;8:48.10.3389/fcell.2020.00048Search in Google Scholar

[3] Sicklick JK, Kato S, Okamura R, Schwaederle M, Hahn ME, Williams CB, et al. Molecular profiling of cancer patients enables personalized combination therapy: the I-PREDICT study. Nat Med. 2019;25(5):744–50.10.1038/s41591-019-0407-5Search in Google Scholar

[4] Griffith M, Spies NC, Krysiak K, McMichael JF, Coffman AC, Danos AM, et al. CIViC is a community knowledge base for expert crowdsourcing the clinical interpretation of variants in cancer. Nat Genet. 2017;49(2):170–4.10.1038/ng.3774Search in Google Scholar

[5] Chakravarty D, Gao J, Phillips SM, Phillips SM, Kundra R, Zhang H, et al. OncoKB: a precision oncology knowledge base. JCO Precis Oncol. 2017;1:1–16.10.1200/PO.17.00011Search in Google Scholar

[6] Gray SW, Hicks-Courant K, Cronin A, Rollins BJ, Weeks JC. Physicians’ attitudes about multiplex tumor genomic testing. J Clin Oncol. 2014;32(13):1317–23.10.1200/JCO.2013.52.4298Search in Google Scholar

[7] Den Dunnen JT, Dalgleish R, Maglott DR, Hart RK, Greenblatt MS, McGowan-Jordan J, et al. HGVS recommendations for the description of sequence variants: 2016 update. Hum Mutat. 2016;37(6):564–9.10.1002/humu.22981Search in Google Scholar

[8] Den Dunnen JT, Antonarakis SE. Mutation nomenclature extensions and suggestions to describe complex mutations: a discussion. Hum Mutat. 2000;15(1):7–12.10.1002/(SICI)1098-1004(200001)15:1<7::AID-HUMU4>3.0.CO;2-NSearch in Google Scholar

[9] Li MM, Datto M, Duncavage EJ, Kulkarni S, Lindeman NI, Roy S, et al. Standards and guidelines for the interpretation and reporting of sequence variants in cancer: a joint consensus recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists. J Mol Diagn. 2017;19(1):4–23.10.1016/j.jmoldx.2016.10.002Search in Google Scholar

[10] Mateo J, Chakravarty D, Dienstmann R, Jezdic S, Gonzalez-Perez A, Lopez-Bigas N, et al. A framework to rank genomic alterations as targets for cancer precision medicine: the esmo scale for clinical actionability of molecular targets (ESCAT). Ann Oncol. 2018;29(9):1895–902.10.1093/annonc/mdy263Search in Google Scholar

[11] Langmuir PB, Yver A. Vandetanib for the treatment of thyroid cancer. Clin Pharmacol Ther. 2012;91(1):71–80.10.1038/clpt.2011.272Search in Google Scholar PubMed

[12] Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S, et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature. 2007;448(7153):561–6.10.1038/nature05945Search in Google Scholar PubMed

[13] Kwak EL, Bang YJ, Camidge DR, Shaw AT, Solomon B, Maki RG, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010;363(18):1693–703.10.1056/NEJMoa1006448Search in Google Scholar PubMed PubMed Central

[14] Hsiao SY, He HL, Weng TS, Lin CY, Chao CM, Huang WT, et al. Colorectal cancer with EML4-ALK fusion gene response to alectinib: a case report and review of the literature. Case Rep Oncol. 2021;14(1):232–8.10.1159/000511069Search in Google Scholar PubMed PubMed Central

[15] Hu J, Zhang B, Yao F, Fu Y, Chen D, Li D, et al. Acquired multiple mutations ALK I1171N, L1196M and G1202R mediate lorlatinib resistance in EML4-ALK-rearranged malignant pleural mesothelioma: a case report. Ther Adv Respir Dis. 2020;14:1753466620935770.10.1177/1753466620935770Search in Google Scholar PubMed PubMed Central

[16] Godbert Y, de Figueiredo BH, Bonichon F, Chibon F, Hostein I, Pérot G, et al. Remarkable response to crizotinib in woman with anaplastic lymphoma kinase-rearranged anaplastic thyroid carcinoma. J Clin Oncol. 2015;33(20):e84–7.10.1200/JCO.2013.49.6596Search in Google Scholar PubMed

[17] Zhou Y, Lizaso A, Mao X, Yang N, Zhang Y. Novel AMBRA1-ALK fusion identified by next-generation sequencing in advanced gallbladder cancer responds to crizotinib: a case report. Ann Transl Med. 2020;8(17):1099.10.21037/atm-20-1007Search in Google Scholar PubMed PubMed Central

[18] Hui B, Zhang J, Shi X, Xing F, Shao YW, Wang Y, et al. EML4-ALK, a potential therapeutic target that responds to alectinib in ovarian cancer. Jpn J Clin Oncol. 2020;50(12):1470–4.10.1093/jjco/hyaa156Search in Google Scholar PubMed

[19] Zhao P, Peng L, Wu W, Zheng Y, Jiang W, Zhang H, et al. Carcinoma of unknown primary with EML4-ALK fusion response to ALK inhibitors. Oncologist. 2019;24(4):449–54.10.1634/theoncologist.2018-0439Search in Google Scholar PubMed PubMed Central

[20] Yakirevich E, Resnick MB, Mangray S, Wheeler M, Jackson CL, Lombardo KA, et al. Oncogenic ALK fusion in rare and aggressive subtype of colorectal adenocarcinoma as a potential therapeutic target. Clin Cancer Res. 2016;22(15):3831–40.10.1158/1078-0432.CCR-15-3000Search in Google Scholar PubMed

[21] Amatu A, Somaschini A, Cerea G, Bosotti R, Valtorta E, Buonandi P, et al. Novel CAD-ALK gene rearrangement is drugable by entrectinib in colorectal cancer. Br J Cancer. 2015;113(12):1730–4.10.1038/bjc.2015.401Search in Google Scholar PubMed PubMed Central

[22] Templeton AJ, Dutoit V, Cathomas R, Rothermundt C, Bärtschi D, Dröge C, et al. Phase 2 trial of single-agent everolimus in chemotherapy-naive patients with castration-resistant prostate cancer (SAKK 08/08). Eur Urol. 2013;64(1):150–8.10.1016/j.eururo.2013.03.040Search in Google Scholar PubMed

[23] Doi T, Shitara K, Kojima T, Kuboki Y, Matsubara N, Bando H, et al. Phase I study of the irreversible fibroblast growth factor receptor 1–4 inhibitor futibatinib in Japanese patients with advanced solid tumors. Cancer Sci. 2023;114(2):574.10.1111/cas.15486Search in Google Scholar PubMed PubMed Central

[24] Meric-Bernstam F, Bahleda R, Hierro C, Sanson M, Bridgewater J, Arkenau H, et al. Futibatinib, an irreversible FGFR1–4 inhibitor, in patients with advanced solid tumors harboring FGF/FGFR aberrations: a phase I dose-expansion study. Cancer Discovery. 2022;12(2):402–15.10.1158/2159-8290.CD-21-0697Search in Google Scholar PubMed PubMed Central

[25] Mizuta H, Okada K, Araki M, Adachi J, Takemoto A, Kutkowska J, et al. Gilteritinib overcomes lorlatinib resistance in ALK-rearranged cancer. Nat Commun. 2021;12(1):1261.10.1038/s41467-021-21396-wSearch in Google Scholar PubMed PubMed Central

[26] Mologni L, Ceccon M, Pirola A, Chiriano G, Piazza R, Scapozza L, et al. NPM/ALK mutants resistant to ASP3026 display variable sensitivity to alternative ALK inhibitors but succumb to the novel compound PF-06463922. Oncotarget. 2015;6(8):5720–34.10.18632/oncotarget.3122Search in Google Scholar PubMed PubMed Central

[27] Gainor JF, Dardaei L, Yoda S, Friboulet L, Leshchiner I, Katayama R, et al. Molecular mechanisms of resistance to first-and second-generation ALK inhibitors in ALK-rearranged lung cancer. Cancer Discovery. 2016;6(10):1118–33.10.1158/2159-8290.CD-16-0596Search in Google Scholar PubMed PubMed Central

[28] Yoshimura Y, Kurasawa M, Yorozu K, Puig O, Bordogna W, Harada N. Antitumor activity of alectinib, a selective ALK inhibitor, in an ALK-positive NSCLC cell line harboring G1269A mutation: efficacy of alectinib against ALK G1269A mutated cells. Cancer Chemother Pharmacol. 2016;77(3):623–8.10.1007/s00280-016-2977-ySearch in Google Scholar PubMed

[29] Kim S, Kim TM, Kim DW, Go H, Keam B, Lee SH, et al. Heterogeneity of genetic changes associated with acquired crizotinib resistance in ALK-rearranged lung cancer. J Thorac Oncol. 2013;8(4):415–22.10.1097/JTO.0b013e318283dcc0Search in Google Scholar PubMed

[30] Fontana D, Ceccon M, Gambacorti-Passerini C, Mologni L. Activity of second-generation ALK inhibitors against crizotinib-resistant mutants in an NPM-ALK model compared to EML4-ALK. Cancer Med. 2015;4(7):953–65.10.1002/cam4.413Search in Google Scholar PubMed PubMed Central

[31] Amin AD, Li L, Rajan SS, Gokhale V, Groysman MJ, Pongtornpipat P, et al. TKI sensitivity patterns of novel kinase-domain mutations suggest therapeutic opportunities for patients with resistant ALK + tumors. Oncotarget. 2016;7(17):23715–29.10.18632/oncotarget.8173Search in Google Scholar PubMed PubMed Central

[32] Yang Y, Huang J, Wang T, Zhou J, Zheng J, Feng J, et al. Decoding the evolutionary response to ensartinib in patients with ALK-positive NSCLC by dynamic circulating tumor DNA sequencing. J Thorac Oncol. 2021;16(5):827–39.10.1016/j.jtho.2021.01.1615Search in Google Scholar PubMed

[33] Yang Y, Zhou J, Zhou J, Feng J, Zhuang W, Chen J, et al. Efficacy, safety, and biomarker analysis of ensartinib in crizotinib-resistant, ALK-positive non-small-cell lung cancer: a multicentre, phase 2 trial. Lancet Respir Med. 2020;8(1):45–53.10.1016/S2213-2600(19)30252-8Search in Google Scholar PubMed

[34] Wu L, Yao H, Chen H, Wang A, Guo K, Gou W, et al. Landscape of somatic alterations in large-scale solid tumors from an Asian population. Nat Commun. 2022;13(1):4264.10.1038/s41467-022-31780-9Search in Google Scholar PubMed PubMed Central

[35] Choueiri TK, Vaziri SA, Jaeger E, Elson P, Wood L, Bhalla IP, et al. von Hippel-Lindau gene status and response to vascular endothelial growth factor targeted therapy for metastatic clear cell renal cell carcinoma. J Urol. 2008;180(3):860–6.10.1016/j.juro.2008.05.015Search in Google Scholar PubMed

[36] Smith BD, Kaufman MD, Lu WP, Gupta A, Leary CB, Wise SC, et al. Ripretinib (DCC-2618) is a switch control kinase inhibitor of a broad spectrum of oncogenic and drug-resistant KIT and PDGFRA variants. Cancer Cell. 2019;35(5):738–51.10.1016/j.ccell.2019.04.006Search in Google Scholar PubMed

[37] Forbes SA, Beare D, Boutselakis H, Bamford S, Bindal N, Tate J, et al. COSMIC: somatic cancer genetics at high-resolution. Nucleic Acids Res. 2017;45(D1):D777–83.10.1093/nar/gkw1121Search in Google Scholar PubMed PubMed Central

[38] Patterson SE, Liu R, Statz CM, Durkin D, Lakshminarayana A, Mockus SM. The clinical trial landscape in oncology and connectivity of somatic mutational profiles to targeted therapies. Hum Genomics. 2016;10:4.10.1186/s40246-016-0061-7Search in Google Scholar PubMed PubMed Central

[39] Damodaran S, Miya J, Kautto E, Zhu E, Samorodnitsky E, Datta J, et al. Cancer driver log (CanDL): catalog of potentially actionable cancer mutations. J Mol Diagn. 2015;17(5):554–9.10.1016/j.jmoldx.2015.05.002Search in Google Scholar PubMed PubMed Central

[40] Huang L, Fernandes H, Zia H, Tavassoli P, Rennert H, Pisapia D, et al. The cancer precision medicine knowledge base for structured clinical-grade mutations and interpretations. J Am Med Inf Assoc. 2017;24(3):513–9.10.1093/jamia/ocw148Search in Google Scholar PubMed PubMed Central

[41] Voss MH, Chen D, Reising A, Marker M, Shi J, Xu J, et al. PTEN expression, not mutation status in TSC1, TSC2, or mTOR, correlates with the outcome on everolimus in patients with renal cell carcinoma treated on the randomized RECORD-3 trial. Clin Cancer Res. 2019;25(2):506–14.10.1158/1078-0432.CCR-18-1833Search in Google Scholar PubMed

[42] Seront E, Rottey S, Sautois B, Kerger J, D’Hondt LA, Verschaeve V, et al. Phase II study of everolimus in patients with locally advanced or metastatic transitional cell carcinoma of the urothelial tract: clinical activity, molecular response, and biomarkers. Ann Oncol. 2012;23(10):2663–70.10.1093/annonc/mds057Search in Google Scholar PubMed

[43] Soulieres D, Licitra L, Mesía R, Remenár E, Li S, Karpenko A, et al. Molecular alterations and buparlisib efficacy in patients with squamous cell carcinoma of the head and neck: biomarker analysis from BERIL-1. Clin Cancer Res. 2018;24(11):2505–16.10.1158/1078-0432.CCR-17-2644Search in Google Scholar PubMed

Received: 2025-03-17
Revised: 2025-07-28
Accepted: 2025-08-22
Published Online: 2025-10-30

© 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. Suppression of cathepsin B attenuates myocardial injury via limiting cardiomyocyte apoptosis
  156. Influence of sevoflurane combined with propofol anesthesia on the anesthesia effect and adverse reactions in children with acute appendicitis
  157. Identification of hub genes related to acute kidney injury caused by sevoflurane anesthesia and endoplasmic reticulum stress
  158. Efficacy and safety of PD-1/PD-L1 inhibitors in pancreatic ductal adenocarcinoma: a systematic review and Meta-analysis of randomized controlled trials
  159. The value of diagnostic experience in O-RADS MRI score for ovarian-adnexal lesions
  160. Health education pathway for individuals with temporary enterostomies using patient journey mapping
  161. Serum TLR8 as a potential diagnostic biomarker of coronary heart disease
  162. Intraoperative temperature management and its effect on surgical outcomes in elderly patients undergoing lichtenstein unilateral inguinal hernia repair
  163. Immunohistochemical profiling and neuroepithelial heterogeneity in immature ovarian teratomas: a retrospective digital pathology-based study
  164. Associated risk factors and prevalence of human papillomavirus infection among females visiting tertiary care hospital: a cross-sectional study from Nepal
  165. Comparative evaluation of various disc elution methods for the detection of colistin-resistant gram-negative bacteria
  166. Effect of timing of cholecystectomy on weight loss after sleeve gastrectomy in morbidly obese individuals with cholelithiasis: a retrospective cohort study
  167. Causal association between ceramide levels and central precocious puberty: a mendelian randomization study
  168. Novel predictive model for colorectal liver metastases recurrence: a radiomics and clinical data approach
  169. Relationship between resident physicians’ perceived professional value and exposure to violence
  170. Multiple sclerosis and type 1 diabetes: a Mendelian randomization study of European ancestry
  171. Rapid pathogen identification in peritoneal dialysis effluent by MALDI-TOF MS following blood culture enrichment
  172. Comparison of open and percutaneous A1 pulley release in pediatric trigger thumb: a retrospective cohort study
  173. Impact of combined diaphragm-lung ultrasound assessment on postoperative respiratory function in patients under general anesthesia recovery
  174. Development and internal validation of a nomogram for predicting short-term prognosis in ICU patients with acute pyelonephritis
  175. The association between hypoxic burden and blood pressure in patients with obstructive sleep apnea
  176. Promotion of asthenozoospermia by C9orf72 through suppression of spermatogonia activity via fructose metabolism and mitophagy
  177. Review Articles
  178. The effects of enhanced external counter-pulsation on post-acute sequelae of COVID-19: A narrative review
  179. Diabetes-related cognitive impairment: Mechanisms, symptoms, and treatments
  180. Microscopic changes and gross morphology of placenta in women affected by gestational diabetes mellitus in dietary treatment: A systematic review
  181. Review of mechanisms and frontier applications in IL-17A-induced hypertension
  182. Research progress on the correlation between islet amyloid peptides and type 2 diabetes mellitus
  183. 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
  184. The application of augmented reality in robotic general surgery: A mini-review
  185. The effect of Greek mountain tea extract and wheat germ extract on peripheral blood flow and eicosanoid metabolism in mammals
  186. Neurogasobiology of migraine: Carbon monoxide, hydrogen sulfide, and nitric oxide as emerging pathophysiological trinacrium relevant to nociception regulation
  187. Plant polyphenols, terpenes, and terpenoids in oral health
  188. Laboratory medicine between technological innovation, rights safeguarding, and patient safety: A bioethical perspective
  189. End-of-life in cancer patients: Medicolegal implications and ethical challenges in Europe
  190. The maternal factors during pregnancy for intrauterine growth retardation: An umbrella review
  191. Intra-abdominal hypertension/abdominal compartment syndrome of pediatric patients in critical care settings
  192. PI3K/Akt pathway and neuroinflammation in sepsis-associated encephalopathy
  193. Screening of Group B Streptococcus in pregnancy: A systematic review for the laboratory detection
  194. Giant borderline ovarian tumours – review of the literature
  195. Leveraging artificial intelligence for collaborative care planning: Innovations and impacts in shared decision-making – A systematic review
  196. Cholera epidemiology analysis through the experience of the 1973 Naples epidemic
  197. Risk factors of frailty/sarcopenia in community older adults: Meta-analysis
  198. Supplement strategies for infertility in overweight women: Evidence and legal insights
  199. Scurvy, a not obsolete disorder: Clinical report in eight young children and literature review
  200. A meta-analysis of the effects of DBS on cognitive function in patients with advanced PD
  201. Protective role of selenium in sepsis: Mechanisms and potential therapeutic strategies
  202. Strategies for hyperkalemia management in dialysis patients: A systematic review
  203. C-reactive protein-to-albumin ratio in peripheral artery disease
  204. Research progress on autophagy and its roles in sepsis induced organ injury
  205. Neuronutrition in autism spectrum disorders
  206. Pumilio 2 in neural development, function, and specific neurological disorders
  207. Antibiotic prescribing patterns in general dental practice- a scoping review
  208. Clinical and medico-legal reflections on non-invasive prenatal testing
  209. Smartphone use and back pain: a narrative review of postural pathologies
  210. Targeting endothelial oxidative stress in hypertension
  211. Exploring links between acne and metabolic syndrome: a narrative review
  212. Case Reports
  213. Delayed graft function after renal transplantation
  214. Semaglutide treatment for type 2 diabetes in a patient with chronic myeloid leukemia: A case report and review of the literature
  215. Diverse electrophysiological demyelinating features in a late-onset glycogen storage disease type IIIa case
  216. Giant right atrial hemangioma presenting with ascites: A case report
  217. Laser excision of a large granular cell tumor of the vocal cord with subglottic extension: A case report
  218. EsoFLIP-assisted dilation for dysphagia in systemic sclerosis: Highlighting the role of multimodal esophageal evaluation
  219. Molecular hydrogen-rhodiola as an adjuvant therapy for ischemic stroke in internal carotid artery occlusion: A case report
  220. Coronary artery anomalies: A case of the “malignant” left coronary artery and its surgical management
  221. Combined VAT and retroperitoneoscopy for pleural empyema due to nephro-pleuric fistula in xanthogranulomatous pyelonephritis
  222. A rare case of Opalski syndrome with a suspected multiple sclerosis etiology
  223. Newly diagnosed B-cell acute lymphoblastic leukemia demonstrating localized bone marrow infiltration exclusively in the lower extremities
  224. Rapid Communication
  225. Biological properties of valve materials using RGD and EC
  226. A single oral administration of flavanols enhances short-term memory in mice along with increased brain-derived neurotrophic factor
  227. Repeat influenza incidence across two consecutive influenza seasons
  228. Letter to the Editor
  229. Role of enhanced external counterpulsation in long COVID
  230. Expression of Concern
  231. Expression of concern “A ceRNA network mediated by LINC00475 in papillary thyroid carcinoma”
  232. Expression of concern “Notoginsenoside R1 alleviates spinal cord injury through the miR-301a/KLF7 axis to activate Wnt/β-catenin pathway”
  233. Expression of concern “circ_0020123 promotes cell proliferation and migration in lung adenocarcinoma via PDZD8”
  234. Corrigendum
  235. Corrigendum to “Empagliflozin improves aortic injury in obese mice by regulating fatty acid metabolism”
  236. Corrigendum to “Comparing the therapeutic efficacy of endoscopic minimally invasive surgery and traditional surgery for early-stage breast cancer: A meta-analysis”
  237. Corrigendum to “The progress of autoimmune hepatitis research and future challenges”
  238. Retraction
  239. Retraction of “miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway”
  240. Retraction of: “LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through downregulating SP-A by sponging to miR-424”
  241. Retraction of: “SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways”
  242. Special Issue Advancements in oncology: bridging clinical and experimental research - Part II
  243. Unveiling novel biomarkers for platinum chemoresistance in ovarian cancer
  244. Lathyrol affects the expression of AR and PSA and inhibits the malignant behavior of RCC cells
  245. The era of increasing cancer survivorship: Trends in fertility preservation, medico-legal implications, and ethical challenges
  246. Bone scintigraphy and positron emission tomography in the early diagnosis of MRONJ
  247. Meta-analysis of clinical efficacy and safety of immunotherapy combined with chemotherapy in non-small cell lung cancer
  248. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part IV
  249. Exploration of mRNA-modifying METTL3 oncogene as momentous prognostic biomarker responsible for colorectal cancer development
  250. Special Issue The evolving saga of RNAs from bench to bedside - Part III
  251. Interaction and verification of ferroptosis-related RNAs Rela and Stat3 in promoting sepsis-associated acute kidney injury
  252. The mRNA MOXD1: Link to oxidative stress and prognostic significance in gastric cancer
  253. Special Issue Exploring the biological mechanism of human diseases based on MultiOmics Technology - Part II
  254. Dynamic changes in lactate-related genes in microglia and their role in immune cell interactions after ischemic stroke
  255. A prognostic model correlated with fatty acid metabolism in Ewing’s sarcoma based on bioinformatics analysis
  256. Red cell distribution width predicts early kidney injury: A NHANES cross-sectional study
  257. Special Issue Diabetes mellitus: pathophysiology, complications & treatment
  258. Nutritional risk assessment and nutritional support in children with congenital diabetes during surgery
  259. Correlation of the differential expressions of RANK, RANKL, and OPG with obesity in the elderly population in Xinjiang
  260. A discussion on the application of fluorescence micro-optical sectioning tomography in the research of cognitive dysfunction in diabetes
  261. A review of brain research on T2DM-related cognitive dysfunction
  262. Metformin and estrogen modulation in LABC with T2DM: A 36-month randomized trial
  263. Special Issue Innovative Biomarker Discovery and Precision Medicine in Cancer Diagnostics
  264. CircASH1L-mediated tumor progression in triple-negative breast cancer: PI3K/AKT pathway mechanisms
https://doi.org/10.1515/med-2025-1289
Keywords for this article
precision oncology; tumor knowledge base; genomic alterations; classification system; weighted evidence analysis
Creative Commons
BY 4.0

Articles in the same Issue

  1. Research Articles
  2. Network pharmacological analysis and in vitro testing of the rutin effects on triple-negative breast cancer
  3. Impact of diabetes on long-term survival in elderly liver cancer patients: A retrospective study
  4. Knockdown of CCNB1 alleviates high glucose-triggered trophoblast dysfunction during gestational diabetes via Wnt/β-catenin signaling pathway
  5. Risk factors for severe adverse drug reactions in hospitalized patients
  6. Analysis of the effect of ALA-PDT on macrophages in footpad model of mice infected with Fonsecaea monophora based on single-cell sequencing
  7. Development and validation of headspace gas chromatography with a flame ionization detector method for the determination of ethanol in the vitreous humor
  8. CMSP exerts anti-tumor effects on small cell lung cancer cells by inducing mitochondrial dysfunction and ferroptosis
  9. Predictive value of plasma sB7-H3 and YKL-40 in pediatric refractory Mycoplasma pneumoniae pneumonia
  10. Antiangiogenic potential of Elaeagnus umbellata extracts and molecular docking study by targeting VEGFR-2 pathway
  11. Comparison of the effectiveness of nurse-led preoperative counseling and postoperative follow-up care vs standard care for patients with gastric cancer
  12. Comparing the therapeutic efficacy of endoscopic minimally invasive surgery and traditional surgery for early-stage breast cancer: A meta-analysis
  13. Adhered macrophages as an additional marker of cardiomyocyte injury in biopsies of patients with dilated cardiomyopathy
  14. Association between statin administration and outcome in patients with sepsis: A retrospective study
  15. Exploration of the association between estimated glucose disposal rate and osteoarthritis in middle-aged and older adults: An analysis of NHANES data from 2011 to 2018
  16. A comparative analysis of the binary and multiclass classified chest X-ray images of pneumonia and COVID-19 with ML and DL models
  17. Lysophosphatidic acid 2 alleviates deep vein thrombosis via protective endothelial barrier function
  18. Transcription factor A, mitochondrial promotes lymph node metastasis and lymphangiogenesis in epithelial ovarian carcinoma
  19. Serum PM20D1 levels are associated with nutritional status and inflammatory factors in gastric cancer patients undergoing early enteral nutrition
  20. Hydromorphone reduced the incidence of emergence agitation after adenotonsillectomy in children with obstructive sleep apnea: A randomized, double-blind study
  21. Vitamin D replacement therapy may regulate sleep habits in patients with restless leg syndrome
  22. The first-line antihypertensive nitrendipine potentiated the therapeutic effect of oxaliplatin by downregulating CACNA1D in colorectal cancer
  23. Health literacy and health-related quality of life: The mediating role of irrational happiness
  24. Modulatory effects of Lycium barbarum polysaccharide on bone cell dynamics in osteoporosis
  25. Mechanism research on inhibition of gastric cancer in vitro by the extract of Pinellia ternata based on network pharmacology and cellular metabolomics
  26. Examination of the causal role of immune cells in non-alcoholic fatty liver disease by a bidirectional Mendelian randomization study
  27. Clinical analysis of ten cases of HIV infection combined with acute leukemia
  28. Investigating the cardioprotective potential of quercetin against tacrolimus-induced cardiotoxicity in Wistar rats: A mechanistic insights
  29. Clinical observation of probiotics combined with mesalazine and Yiyi Baitouweng Decoction retention enema in treating mild-to-moderate ulcerative colitis
  30. Diagnostic value of ratio of blood inflammation to coagulation markers in periprosthetic joint infection
  31. Sex-specific associations of sex hormone binding globulin and risk of bladder cancer
  32. Core muscle strength and stability-oriented breathing training reduces inter-recti distance in postpartum women
  33. The ERAS nursing care strategy for patients undergoing transsphenoidal endoscopic pituitary tumor resection: A randomized blinded controlled trial
  34. The serum IL-17A levels in patients with traumatic bowel rupture post-surgery and its predictive value for patient prognosis
  35. Impact of Kolb’s experiential learning theory-based nursing on caregiver burden and psychological state of caregivers of dementia patients
  36. Analysis of serum NLR combined with intraoperative margin condition to predict the prognosis of cervical HSIL patients undergoing LEEP surgery
  37. Commiphora gileadensis ameliorate infertility and erectile dysfunction in diabetic male mice
  38. The correlation between epithelial–mesenchymal transition classification and MMP2 expression of circulating tumor cells and prognosis of advanced or metastatic nasopharyngeal carcinoma
  39. Tetrahydropalmatine improves mitochondrial function in vascular smooth muscle cells of atherosclerosis in vitro by inhibiting Ras homolog gene family A/Rho-associated protein kinase-1 signaling pathway
  40. A cross-sectional study: Relationship between serum oxidative stress levels and arteriovenous fistula maturation in maintenance dialysis patients
  41. A comparative analysis of the impact of repeated administration of flavan 3-ol on brown, subcutaneous, and visceral adipose tissue
  42. Identifying early screening factors for depression in middle-aged and older adults: A cohort study
  43. Perform tumor-specific survival analysis for Merkel cell carcinoma patients undergoing surgical resection based on the SEER database by constructing a nomogram chart
  44. Unveiling the role of CXCL10 in pancreatic cancer progression: A novel prognostic indicator
  45. High-dose preoperative intraperitoneal erythropoietin and intravenous methylprednisolone in acute traumatic spinal cord injuries following decompression surgeries
  46. RAB39B: A novel biomarker for acute myeloid leukemia identified via multi-omics and functional validation
  47. Impact of peripheral conditioning on reperfusion injury following primary percutaneous coronary intervention in diabetic and non-diabetic STEMI patients
  48. Clinical efficacy of azacitidine in the treatment of middle- and high-risk myelodysplastic syndrome in middle-aged and elderly patients: A retrospective study
  49. The effect of ambulatory blood pressure load on mitral regurgitation in continuous ambulatory peritoneal dialysis patients
  50. Expression and clinical significance of ITGA3 in breast cancer
  51. Single-nucleus RNA sequencing reveals ARHGAP28 expression of podocytes as a biomarker in human diabetic nephropathy
  52. rSIG combined with NLR in the prognostic assessment of patients with multiple injuries
  53. Toxic metals and metalloids in collagen supplements of fish and jellyfish origin: Risk assessment for daily intake
  54. Exploring causal relationship between 41 inflammatory cytokines and marginal zone lymphoma: A bidirectional Mendelian randomization study
  55. Gender beliefs and legitimization of dating violence in adolescents
  56. Effect of serum IL-6, CRP, and MMP-9 levels on the efficacy of modified preperitoneal Kugel repair in patients with inguinal hernia
  57. Effect of smoking and smoking cessation on hematological parameters in polycythemic patients
  58. Pathogen surveillance and risk factors for pulmonary infection in patients with lung cancer: A retrospective single-center study
  59. Necroptosis of hippocampal neurons in paclitaxel chemotherapy-induced cognitive impairment mediates microglial activation via TLR4/MyD88 signaling pathway
  60. Celastrol suppresses neovascularization in rat aortic vascular endothelial cells stimulated by inflammatory tenocytes via modulating the NLRP3 pathway
  61. Cord-lamina angle and foraminal diameter as key predictors of C5 palsy after anterior cervical decompression and fusion surgery
  62. GATA1: A key biomarker for predicting the prognosis of patients with diffuse large B-cell lymphoma
  63. Influencing factors of false lumen thrombosis in type B aortic dissection: A single-center retrospective study
  64. MZB1 regulates the immune microenvironment and inhibits ovarian cancer cell migration
  65. Integrating experimental and network pharmacology to explore the pharmacological mechanisms of Dioscin against glioblastoma
  66. Trends in research on preterm birth in twin pregnancy based on bibliometrics
  67. Four-week IgE/baseline IgE ratio combined with tryptase predicts clinical outcome in omalizumab-treated children with moderate-to-severe asthma
  68. Single-cell transcriptomic analysis identifies a stress response Schwann cell subtype
  69. Acute pancreatitis risk in the diagnosis and management of inflammatory bowel disease: A critical focus
  70. Effect of subclinical esketamine on NLRP3 and cognitive dysfunction in elderly ischemic stroke patients
  71. Interleukin-37 mediates the anti-oral tumor activity in oral cancer through STAT3
  72. CA199 and CEA expression levels, and minimally invasive postoperative prognosis analysis in esophageal squamous carcinoma patients
  73. Efficacy of a novel drainage catheter in the treatment of CSF leak after posterior spine surgery: A retrospective cohort study
  74. Comprehensive biomedicine assessment of Apteranthes tuberculata extracts: Phytochemical analysis and multifaceted pharmacological evaluation in animal models
  75. Relation of time in range to severity of coronary artery disease in patients with type 2 diabetes: A cross-sectional study
  76. Dopamine attenuates ethanol-induced neuronal apoptosis by stimulating electrical activity in the developing rat retina
  77. Correlation between albumin levels during the third trimester and the risk of postpartum levator ani muscle rupture
  78. Factors associated with maternal attention and distraction during breastfeeding and childcare: A cross-sectional study in the west of Iran
  79. Mechanisms of hesperetin in treating metabolic dysfunction-associated steatosis liver disease via network pharmacology and in vitro experiments
  80. The law on oncological oblivion in the Italian and European context: How to best uphold the cancer patients’ rights to privacy and self-determination?
  81. The prognostic value of the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and prognostic nutritional index for survival in patients with colorectal cancer
  82. Factors affecting the measurements of peripheral oxygen saturation values in healthy young adults
  83. Comparison and correlations between findings of hysteroscopy and vaginal color Doppler ultrasonography for detection of uterine abnormalities in patients with recurrent implantation failure
  84. The effects of different types of RAGT on balance function in stroke patients with low levels of independent walking in a convalescent rehabilitation hospital
  85. Causal relationship between asthma and ankylosing spondylitis: A bidirectional two-sample univariable and multivariable Mendelian randomization study
  86. Correlations of health literacy with individuals’ understanding and use of medications in Southern Taiwan
  87. Correlation of serum calprotectin with outcome of acute cerebral infarction
  88. Comparison of computed tomography and guided bronchoscopy in the diagnosis of pulmonary nodules: A systematic review and meta-analysis
  89. Curdione protects vascular endothelial cells and atherosclerosis via the regulation of DNMT1-mediated ERBB4 promoter methylation
  90. The identification of novel missense variant in ChAT gene in a patient with gestational diabetes denotes plausible genetic association
  91. Molecular genotyping of multi-system rare blood types in foreign blood donors based on DNA sequencing and its clinical significance
  92. Exploring the role of succinyl carnitine in the association between CD39⁺ CD4⁺ T cell and ulcerative colitis: A Mendelian randomization study
  93. Dexmedetomidine suppresses microglial activation in postoperative cognitive dysfunction via the mmu-miRNA-125/TRAF6 signaling axis
  94. Analysis of serum metabolomics in patients with different types of chronic heart failure
  95. Diagnostic value of hematological parameters in the early diagnosis of acute cholecystitis
  96. Pachymaran alleviates fat accumulation, hepatocyte degeneration, and injury in mice with nonalcoholic fatty liver disease
  97. Decrease in CD4 and CD8 lymphocytes are predictors of severe clinical picture and unfavorable outcome of the disease in patients with COVID-19
  98. METTL3 blocked the progression of diabetic retinopathy through m6A-modified SOX2
  99. The predictive significance of anti-RO-52 antibody in patients with interstitial pneumonia after treatment of malignant tumors
  100. Exploring cerebrospinal fluid metabolites, cognitive function, and brain atrophy: Insights from Mendelian randomization
  101. Development and validation of potential molecular subtypes and signatures of ocular sarcoidosis based on autophagy-related gene analysis
  102. Widespread venous thrombosis: Unveiling a complex case of Behçet’s disease with a literature perspective
  103. Uterine fibroid embolization: An analysis of clinical outcomes and impact on patients’ quality of life
  104. Discovery of lipid metabolism-related diagnostic biomarkers and construction of diagnostic model in steroid-induced osteonecrosis of femoral head
  105. Serum-derived exomiR-188-3p is a promising novel biomarker for early-stage ovarian cancer
  106. Enhancing chronic back pain management: A comparative study of ultrasound–MRI fusion guidance for paravertebral nerve block
  107. Peptide CCAT1-70aa promotes hepatocellular carcinoma proliferation and invasion via the MAPK/ERK pathway
  108. Electroacupuncture-induced reduction of myocardial ischemia–reperfusion injury via FTO-dependent m6A methylation modulation
  109. Hemorrhoids and cardiovascular disease: A bidirectional Mendelian randomization study
  110. Cell-free adipose extract inhibits hypertrophic scar formation through collagen remodeling and antiangiogenesis
  111. HALP score in Demodex blepharitis: A case–control study
  112. Assessment of SOX2 performance as a marker for circulating cancer stem-like cells (CCSCs) identification in advanced breast cancer patients using CytoTrack system
  113. Risk and prognosis for brain metastasis in primary metastatic cervical cancer patients: A population-based study
  114. Comparison of the two intestinal anastomosis methods in pediatric patients
  115. Factors influencing hematological toxicity and adverse effects of perioperative hyperthermic intraperitoneal vs intraperitoneal chemotherapy in gastrointestinal cancer
  116. Endotoxin tolerance inhibits NLRP3 inflammasome activation in macrophages of septic mice by restoring autophagic flux through TRIM26
  117. Lateral transperitoneal laparoscopic adrenalectomy: A single-centre experience of 21 procedures
  118. Petunidin attenuates lipopolysaccharide-induced retinal microglia inflammatory response in diabetic retinopathy by targeting OGT/NF-κB/LCN2 axis
  119. Procalcitonin and C-reactive protein as biomarkers for diagnosing and assessing the severity of acute cholecystitis
  120. Factors determining the number of sessions in successful extracorporeal shock wave lithotripsy patients
  121. Development of a nomogram for predicting cancer-specific survival in patients with renal pelvic cancer following surgery
  122. Inhibition of ATG7 promotes orthodontic tooth movement by regulating the RANKL/OPG ratio under compression force
  123. A machine learning-based prognostic model integrating mRNA stemness index, hypoxia, and glycolysis‑related biomarkers for colorectal cancer
  124. Glutathione attenuates sepsis-associated encephalopathy via dual modulation of NF-κB and PKA/CREB pathways
  125. FAHD1 prevents neuronal ferroptosis by modulating R-loop and the cGAS–STING pathway
  126. Association of placenta weight and morphology with term low birth weight: A case–control study
  127. Investigation of the pathogenic variants induced Sjogren’s syndrome in Turkish population
  128. Nucleotide metabolic abnormalities in post-COVID-19 condition and type 2 diabetes mellitus patients and their association with endocrine dysfunction
  129. TGF-β–Smad2/3 signaling in high-altitude pulmonary hypertension in rats: Role and mechanisms via macrophage M2 polarization
  130. Ultrasound-guided unilateral versus bilateral erector spinae plane block for postoperative analgesia of patients undergoing laparoscopic cholecystectomy
  131. Profiling gut microbiome dynamics in subacute thyroiditis: Implications for pathogenesis, diagnosis, and treatment
  132. Delta neutrophil index, CRP/albumin ratio, procalcitonin, immature granulocytes, and HALP score in acute appendicitis: Best performing biomarker?
  133. Anticancer activity mechanism of novelly synthesized and characterized benzofuran ring-linked 3-nitrophenyl chalcone derivative on colon cancer cells
  134. H2valdien3 arrests the cell cycle and induces apoptosis of gastric cancer
  135. Prognostic relevance of PRSS2 and its immune correlates in papillary thyroid carcinoma
  136. Association of SGLT2 inhibition with psychiatric disorders: A Mendelian randomization study
  137. Motivational interviewing for alcohol use reduction in Thai patients
  138. Luteolin alleviates oxygen-glucose deprivation/reoxygenation-induced neuron injury by regulating NLRP3/IL-1β signaling
  139. Polyphyllin II inhibits thyroid cancer cell growth by simultaneously inhibiting glycolysis and oxidative phosphorylation
  140. Relationship between the expression of copper death promoting factor SLC31A1 in papillary thyroid carcinoma and clinicopathological indicators and prognosis
  141. CSF2 polarized neutrophils and invaded renal cancer cells in vitro influence
  142. Proton pump inhibitors-induced thrombocytopenia: A systematic literature analysis of case reports
  143. The current status and influence factors of research ability among community nurses: A sequential qualitative–quantitative study
  144. OKAIN: A comprehensive oncology knowledge base for the interpretation of clinically actionable alterations
  145. The relationship between serum CA50, CA242, and SAA levels and clinical pathological characteristics and prognosis in patients with pancreatic cancer
  146. Identification and external validation of a prognostic signature based on hypoxia–glycolysis-related genes for kidney renal clear cell carcinoma
  147. Engineered RBC-derived nanovesicles functionalized with tumor-targeting ligands: A comparative study on breast cancer targeting efficiency and biocompatibility
  148. Relationship of resting echocardiography combined with serum micronutrients to the severity of low-gradient severe aortic stenosis
  149. Effect of vibration on pain during subcutaneous heparin injection: A randomized, single-blind, placebo-controlled trial
  150. The diagnostic performance of machine learning-based FFRCT for coronary artery disease: A meta-analysis
  151. Comparing biofeedback device vs diaphragmatic breathing for bloating relief: A randomized controlled trial
  152. Serum uric acid to albumin ratio and C-reactive protein as predictive biomarkers for chronic total occlusion and coronary collateral circulation quality
  153. Multiple organ scoring systems for predicting in-hospital mortality of sepsis patients in the intensive care unit
  154. Single-cell RNA sequencing data analysis of the inner ear in gentamicin-treated mice via intraperitoneal injection
  155. Suppression of cathepsin B attenuates myocardial injury via limiting cardiomyocyte apoptosis
  156. Influence of sevoflurane combined with propofol anesthesia on the anesthesia effect and adverse reactions in children with acute appendicitis
  157. Identification of hub genes related to acute kidney injury caused by sevoflurane anesthesia and endoplasmic reticulum stress
  158. Efficacy and safety of PD-1/PD-L1 inhibitors in pancreatic ductal adenocarcinoma: a systematic review and Meta-analysis of randomized controlled trials
  159. The value of diagnostic experience in O-RADS MRI score for ovarian-adnexal lesions
  160. Health education pathway for individuals with temporary enterostomies using patient journey mapping
  161. Serum TLR8 as a potential diagnostic biomarker of coronary heart disease
  162. Intraoperative temperature management and its effect on surgical outcomes in elderly patients undergoing lichtenstein unilateral inguinal hernia repair
  163. Immunohistochemical profiling and neuroepithelial heterogeneity in immature ovarian teratomas: a retrospective digital pathology-based study
  164. Associated risk factors and prevalence of human papillomavirus infection among females visiting tertiary care hospital: a cross-sectional study from Nepal
  165. Comparative evaluation of various disc elution methods for the detection of colistin-resistant gram-negative bacteria
  166. Effect of timing of cholecystectomy on weight loss after sleeve gastrectomy in morbidly obese individuals with cholelithiasis: a retrospective cohort study
  167. Causal association between ceramide levels and central precocious puberty: a mendelian randomization study
  168. Novel predictive model for colorectal liver metastases recurrence: a radiomics and clinical data approach
  169. Relationship between resident physicians’ perceived professional value and exposure to violence
  170. Multiple sclerosis and type 1 diabetes: a Mendelian randomization study of European ancestry
  171. Rapid pathogen identification in peritoneal dialysis effluent by MALDI-TOF MS following blood culture enrichment
  172. Comparison of open and percutaneous A1 pulley release in pediatric trigger thumb: a retrospective cohort study
  173. Impact of combined diaphragm-lung ultrasound assessment on postoperative respiratory function in patients under general anesthesia recovery
  174. Development and internal validation of a nomogram for predicting short-term prognosis in ICU patients with acute pyelonephritis
  175. The association between hypoxic burden and blood pressure in patients with obstructive sleep apnea
  176. Promotion of asthenozoospermia by C9orf72 through suppression of spermatogonia activity via fructose metabolism and mitophagy
  177. Review Articles
  178. The effects of enhanced external counter-pulsation on post-acute sequelae of COVID-19: A narrative review
  179. Diabetes-related cognitive impairment: Mechanisms, symptoms, and treatments
  180. Microscopic changes and gross morphology of placenta in women affected by gestational diabetes mellitus in dietary treatment: A systematic review
  181. Review of mechanisms and frontier applications in IL-17A-induced hypertension
  182. Research progress on the correlation between islet amyloid peptides and type 2 diabetes mellitus
  183. 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
  184. The application of augmented reality in robotic general surgery: A mini-review
  185. The effect of Greek mountain tea extract and wheat germ extract on peripheral blood flow and eicosanoid metabolism in mammals
  186. Neurogasobiology of migraine: Carbon monoxide, hydrogen sulfide, and nitric oxide as emerging pathophysiological trinacrium relevant to nociception regulation
  187. Plant polyphenols, terpenes, and terpenoids in oral health
  188. Laboratory medicine between technological innovation, rights safeguarding, and patient safety: A bioethical perspective
  189. End-of-life in cancer patients: Medicolegal implications and ethical challenges in Europe
  190. The maternal factors during pregnancy for intrauterine growth retardation: An umbrella review
  191. Intra-abdominal hypertension/abdominal compartment syndrome of pediatric patients in critical care settings
  192. PI3K/Akt pathway and neuroinflammation in sepsis-associated encephalopathy
  193. Screening of Group B Streptococcus in pregnancy: A systematic review for the laboratory detection
  194. Giant borderline ovarian tumours – review of the literature
  195. Leveraging artificial intelligence for collaborative care planning: Innovations and impacts in shared decision-making – A systematic review
  196. Cholera epidemiology analysis through the experience of the 1973 Naples epidemic
  197. Risk factors of frailty/sarcopenia in community older adults: Meta-analysis
  198. Supplement strategies for infertility in overweight women: Evidence and legal insights
  199. Scurvy, a not obsolete disorder: Clinical report in eight young children and literature review
  200. A meta-analysis of the effects of DBS on cognitive function in patients with advanced PD
  201. Protective role of selenium in sepsis: Mechanisms and potential therapeutic strategies
  202. Strategies for hyperkalemia management in dialysis patients: A systematic review
  203. C-reactive protein-to-albumin ratio in peripheral artery disease
  204. Research progress on autophagy and its roles in sepsis induced organ injury
  205. Neuronutrition in autism spectrum disorders
  206. Pumilio 2 in neural development, function, and specific neurological disorders
  207. Antibiotic prescribing patterns in general dental practice- a scoping review
  208. Clinical and medico-legal reflections on non-invasive prenatal testing
  209. Smartphone use and back pain: a narrative review of postural pathologies
  210. Targeting endothelial oxidative stress in hypertension
  211. Exploring links between acne and metabolic syndrome: a narrative review
  212. Case Reports
  213. Delayed graft function after renal transplantation
  214. Semaglutide treatment for type 2 diabetes in a patient with chronic myeloid leukemia: A case report and review of the literature
  215. Diverse electrophysiological demyelinating features in a late-onset glycogen storage disease type IIIa case
  216. Giant right atrial hemangioma presenting with ascites: A case report
  217. Laser excision of a large granular cell tumor of the vocal cord with subglottic extension: A case report
  218. EsoFLIP-assisted dilation for dysphagia in systemic sclerosis: Highlighting the role of multimodal esophageal evaluation
  219. Molecular hydrogen-rhodiola as an adjuvant therapy for ischemic stroke in internal carotid artery occlusion: A case report
  220. Coronary artery anomalies: A case of the “malignant” left coronary artery and its surgical management
  221. Combined VAT and retroperitoneoscopy for pleural empyema due to nephro-pleuric fistula in xanthogranulomatous pyelonephritis
  222. A rare case of Opalski syndrome with a suspected multiple sclerosis etiology
  223. Newly diagnosed B-cell acute lymphoblastic leukemia demonstrating localized bone marrow infiltration exclusively in the lower extremities
  224. Rapid Communication
  225. Biological properties of valve materials using RGD and EC
  226. A single oral administration of flavanols enhances short-term memory in mice along with increased brain-derived neurotrophic factor
  227. Repeat influenza incidence across two consecutive influenza seasons
  228. Letter to the Editor
  229. Role of enhanced external counterpulsation in long COVID
  230. Expression of Concern
  231. Expression of concern “A ceRNA network mediated by LINC00475 in papillary thyroid carcinoma”
  232. Expression of concern “Notoginsenoside R1 alleviates spinal cord injury through the miR-301a/KLF7 axis to activate Wnt/β-catenin pathway”
  233. Expression of concern “circ_0020123 promotes cell proliferation and migration in lung adenocarcinoma via PDZD8”
  234. Corrigendum
  235. Corrigendum to “Empagliflozin improves aortic injury in obese mice by regulating fatty acid metabolism”
  236. Corrigendum to “Comparing the therapeutic efficacy of endoscopic minimally invasive surgery and traditional surgery for early-stage breast cancer: A meta-analysis”
  237. Corrigendum to “The progress of autoimmune hepatitis research and future challenges”
  238. Retraction
  239. Retraction of “miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway”
  240. Retraction of: “LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through downregulating SP-A by sponging to miR-424”
  241. Retraction of: “SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways”
  242. Special Issue Advancements in oncology: bridging clinical and experimental research - Part II
  243. Unveiling novel biomarkers for platinum chemoresistance in ovarian cancer
  244. Lathyrol affects the expression of AR and PSA and inhibits the malignant behavior of RCC cells
  245. The era of increasing cancer survivorship: Trends in fertility preservation, medico-legal implications, and ethical challenges
  246. Bone scintigraphy and positron emission tomography in the early diagnosis of MRONJ
  247. Meta-analysis of clinical efficacy and safety of immunotherapy combined with chemotherapy in non-small cell lung cancer
  248. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part IV
  249. Exploration of mRNA-modifying METTL3 oncogene as momentous prognostic biomarker responsible for colorectal cancer development
  250. Special Issue The evolving saga of RNAs from bench to bedside - Part III
  251. Interaction and verification of ferroptosis-related RNAs Rela and Stat3 in promoting sepsis-associated acute kidney injury
  252. The mRNA MOXD1: Link to oxidative stress and prognostic significance in gastric cancer
  253. Special Issue Exploring the biological mechanism of human diseases based on MultiOmics Technology - Part II
  254. Dynamic changes in lactate-related genes in microglia and their role in immune cell interactions after ischemic stroke
  255. A prognostic model correlated with fatty acid metabolism in Ewing’s sarcoma based on bioinformatics analysis
  256. Red cell distribution width predicts early kidney injury: A NHANES cross-sectional study
  257. Special Issue Diabetes mellitus: pathophysiology, complications & treatment
  258. Nutritional risk assessment and nutritional support in children with congenital diabetes during surgery
  259. Correlation of the differential expressions of RANK, RANKL, and OPG with obesity in the elderly population in Xinjiang
  260. A discussion on the application of fluorescence micro-optical sectioning tomography in the research of cognitive dysfunction in diabetes
  261. A review of brain research on T2DM-related cognitive dysfunction
  262. Metformin and estrogen modulation in LABC with T2DM: A 36-month randomized trial
  263. Special Issue Innovative Biomarker Discovery and Precision Medicine in Cancer Diagnostics
  264. CircASH1L-mediated tumor progression in triple-negative breast cancer: PI3K/AKT pathway mechanisms
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2026 De Gruyter Brill
Downloaded on 4.2.2026 from https://www.degruyterbrill.com/document/doi/10.1515/med-2025-1289/html
Scroll to top button