Methyltransferase-like 13 (METTL13) is a member of the methyltransferase-like (METTL) family characterized by two conserved seven-beta-strand(7BS) catalytic domains. Current evidence identifies METTL13 primarily as a dual protein methyltransferase that modifies the translation elongation factor 1 A(eEF1A), including Lys55 dimethylation and N-terminal methylation. Through this best-established mechanism, METTL13 enhances eEF1A GTPase activity, reshapes translation elongation and codon-specific translational output, and promotes protein production in cells. In multiple cancer settings, METTL13 and the eEF1A-K55 methylation axis are associated with increased translational demand, tumor progression, and Ras-driven tumorigenesis. At the same time, accumulating studies indicate that METTL13 functions are strongly context dependent. Beyond its canonical eEF1A-centered role, METTL13 has been linked to additional regulatory programs, including the c-Cbl/SERCA2a axis, RNA-associated pathways, and disease-specific signaling networks, although these noncanonical mechanisms remain less well defined. Intriguingly, METTL13 may also exert protective or tumor-suppressive effects in selected contexts, such as ischemic heart failure, hereditary deafness, and clear cell renal cell carcinoma. In this narrative review, we summarize the structural and functional features of METTL13, its regulatory network, and current evidence for its roles in malignant and non-malignant diseases. By integrating structural features, molecular modification mechanisms, translational control, disease pathophysiology, and early clinical-translation evidence, this review reframes METTL13 as a context-dependent regulator of proteome adaptation and highlights unresolved mechanistic questions regarding substrate specificity, microenvironment-dependent functional outputs, and context-specific intervention strategies.

Autoimmune regulator (AIRE) enables medullary thymic epithelial cells (mTECs) to express a broad but selective repertoire of tissue-restricted antigens (TRAs), thereby supporting central T-cell tolerance. Recent studies showing that AIRE forms transcriptionally active condensates provide a framework for understanding how chromatin recognition, enhancer-associated cofactor recruitment, three-dimensional genome organization and transcriptional elongation are coordinated during TRA induction. In this view, sparse TRA expression reflects the low probability that a given locus reaches a permissive chromatin and cofactor state, whereas high output may result from local enrichment of BRD4, P-TEFb, Mediator-associated co-activators and elongation machinery after activation. Recent findings on thymic mimetic cells, human thymic spatial organization and peripheral RORγt-associated antigen-presenting cells are discussed as related contexts, with particular attention to the current lack of direct evidence for mTEC-like AIRE condensate mechanisms outside mTECs. Together, these studies place AIRE condensates within a broader regulatory landscape of chromatin gating, transcriptional kinetics and mTEC state diversity.

The tumor microenvironment (TME) is a dynamic and heterogeneous ecosystem whose abnormal vasculature, dense extracellular matrix, metabolic reprogramming and immunosuppression collectively hinder drug penetration, drive therapeutic resistance and limit responses to immunotherapy. TME-responsive nanomedicine provides an emerging toolbox to both monitor and actively remodel the microenvironment for precision cancer therapy. In this narrative review, we first summarize key pathological features of the TME and their impact on drug delivery across classical barriers, including the blood-brain, cutaneous and ocular interfaces, as well as circulating and bone-marrow niches in hematologic malignancies. We then discuss design principles of endogenous and exogenous stimuli-responsive nanoplatforms, and how these systems enable TME monitoring via liquid biopsy, spatial multi-omics and real-time imaging, and TME modulation through metabolic reprogramming, immune activation, vascular normalization and extracellular-matrix remodeling. Finally, we highlight major translational challenges and future opportunities, emphasizing the roles of artificial intelligence, multiscale and quantum-inspired modeling, and closed-loop theranostic strategies in optimizing TME-responsive nanomedicines for clinically meaningful benefit.

BackgroundCervical cancer is a leading cause of gynecologic cancer mortality, especially in low- and middle-income countries. Early detection through screening is essential to reduce incidence and death rates. Advances in high-risk HPV molecular assays, liquid-based cytology (LBC), and AI-assisted diagnostics have transformed screening strategies. However, a systematic, quantitative assessment remains lacking. This study uses cross-database validation and bibliometrics to explore cervical cancer screening trends. It provides insights for clinical practice and future research.MethodologyThis study is a bibliometric analysis rather than a traditional systematic review. We searched Web of Science and PubMed for cervical cancer screening articles from 2000 to 2024. Criteria included clinical trials, systematic reviews, meta-analyses, observational studies, and animal experiments. Conference abstracts and non-academic publications were excluded. After deduplication using CiteSpace, 640 unique articles from PubMed were cross-validated with WoSCC data. We used VOSviewer, CiteSpace, and R for data analysis. Co-occurrence and cluster analysis identified research trends. This bibliometric analysis was reported in accordance with the BIBLIO checklist and informed, where applicable, by the GLOBAL guidance for reporting bibliometric analyses.ObjectivesThe study analyzes research trends in cervical cancer screening using Web of Science and PubMed. It identifies high-frequency keywords, research collaboration networks, technological advances, and geographical patterns. Findings highlight global focus on HPV, cytology, and AI. These trends help guide scientific policy and clinical practices.ResultsThe study includes 1,160 articles from 2000 to 2024, showing a steady increase in publications. The US, China, and India lead in research output. Philip E. Castle is the most prolific author, and Harvard University has the highest citation rate. Core topics include “cervical cancer,” “HPV,” and “screening.” Emerging trends involve “positive women,” “impact,” and “AI.” This signals a shift toward precise and automated screening.ConclusionThe study demonstrates increased academic interest in cervical cancer screening technologies from 2000 to 2024. Research has focused on advancing screening methods, early detection, and effective program implementation. Future efforts should prioritize detection accuracy and enhance accessibility in low-resource settings. We must also standardize clinical protocols for cervical cancer prevention.

Immune imbalance is the core pathophysiological mechanism of the deterioration of β-cell function driven by lipid metabolism disorders. Toll-like receptor 4 (TLR4) inflammatory signaling is a key pathway that mediates lipotoxic injury in β-cells, but the underlying mechanism needs to be further elucidated. Transmembrane protein 24 (TMEM24) is a key transporter that regulates pulsatile insulin secretion, but its pathophysiology in lipotoxicity remains unclear. In this study, we investigate whether TLR4-mediated lipotoxicity is affected by the inhibition of TMEM24 expression. The PPI network shows that TLR4 is associated with both insulin secretion and ER stress proteins in islets from obese rats. Using in vitro lipotoxic β-cell models, we found that TMEM24 is the target signal of palmitic acid (PA)-induced insulin secretion impairment in islet β-cells, and TLR4 plays a mediating role in this process. Mechanistically, TLR4 mediates lipotoxicity by binding to TMEM24 and downregulating its protein expression to suppress PI3K/AKT signaling, leading to β-cell dysfunction. TLR4 knockout ameliorates islet function impairment through TMEM24/PI3K/AKT signaling in HFD-induced obese rats. Taken together, our results show that TLR4 mediates lipotoxicity in islet β-cells by inhibiting the TMEM24/PI3K/AKT pathway, and the mechanism of TLR4-mediated lipotoxicity is elucidated from the perspective of insulin vesicular secretion.

Background: Diabetic foot ulcers (DFU) constitute a major complication arising from diabetes mellitus. Emerging research findings have underscored the pivotal contribution of cellular senescence to the pathophysiological development of wounds exhibiting delayed healing; nevertheless, the molecular regulatory networks governing this process in DFU pathogenesis remain incompletely elucidated. Methods: DFU-related transcriptomic datasets were acquired from public databases. Biomarkers were identified through machine learning algorithms combined with expression validation. To evaluate the diagnostic predictive capacity of identified biomarkers for DFU, a nomogram prediction model was developed and validated. Further analyses included Gene Set Enrichment Analysis (GSEA), molecular network regulation, immune infiltration profiling, and drug prediction. Subsequently, the expression profiles of these biomarkers were quantitatively assessed through reverse transcription quantitative PCR (RT-qPCR) methodology. Results: Four feature genes were identified using machine learning. Among them, CXCR2 and SIGLEC7 passed expression validation and were significantly up-regulated in DFU groups across two datasets (p < 0.05), confirming their potential as biomarkers. A nomogram constructed based on these two biomarkers demonstrated high discriminative accuracy and good calibration (decision curve net benefit > 0, AUC = 0.99). GSEA indicated that CXCR2 and SIGLEC7 were both enriched in the cytokine-cytokine receptor interaction pathway as well as other functionally associated pathways. Molecular regulatory network analysis indicated that both CXCR2 and SIGLEC7 were predicted to be regulated by transcription factors (TFs) such as SOX2. Immune infiltration analysis showed a significant strong positive correlation between CXCR2 and activated mast cells (correlation coefficient (cor) = 0.72, p < 0.001), and between SIGLEC7 and macrophages M0 (cor = 0.71, p < 0.001). Drug prediction identified 12 drugs targeting CXCR2 (e.g., Indoprofen) and one drug targeting SIGLEC7 (N-acetyl-alpha-D-glucosamine). Validation through Reverse Transcription quantitative Polymerase Chain Reaction (RT-qPCR) revealed that CXCR2 and SIGLEC7 expression levels were markedly increased in the DFU group, showing statistically significant differences (p<0.05), which aligned with the bioinformatics analysis outcomes Conclusion: This study identified CXCR2 and SIGLEC7 as SASPRG-related biomarkers in DFU through bioinformatic analysis, providing new theoretical support and a basis for early diagnosis and treatment of DFU. ### Competing Interest Statement The authors have declared no competing interest.

Obstructive sleep apnoea (OSA) and type 2 diabetes mellitus (T2DM) frequently co-occur, with long noncoding RNAs (lncRNAs) implicated in their shared pathophysiology (T2DM-OSA). LncRNA sex determining region Y-box protein 2 (SOX2) overlapping transcript (SOX2OT) is downregulated in diabetic models. This study investigated SOX2OT's regulatory roles using in vivo and in vitro T2DM-OSA models. Intermittent hypoxia (IH) and high glucose (HG) significantly suppressed SOX2OT expression in murine systems and HepG2 hepatocytes. SOX2OT overexpression enhanced glucose consumption and uptake in HG/IH-treated cells by activating insulin receptor substrate/phosphatidylinositol 3-kinase/protein kinase B (IRS/PI3K/AKT) signaling. Concurrently, SOX2OT attenuated oxidative stress (reactive oxygen species (ROS), malondialdehyde (MDA)) while elevating antioxidant activity (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px)), and suppressed inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β)). Mechanistically, SOX2OT functioned as a competing endogenous RNA for microRNA-552-5p (miR-552-5p) to depress SOX2 expression. Crucially, SOX2 knockdown abolished SOX2OT-mediated cytoprotection. Thus, SOX2OT ameliorates insulin resistance in T2DM-OSA through IRS/PI3K/AKT activation and miR-552-5p/SOX2-mediated suppression of oxidative stress and inflammation.

Objectives Bladder carcinoma (BC) is a common malignancy of the urinary tract. As a new hallmark of cancer for drug therapy, RNA-binding proteins (RBPs) are key regulatory factors in alternative splicing events. This work is to uncover the relationship between BC and RBP in order to find drug targets in BC. Methods In this work, data from single-cell RNA-seq GSE1355337, PRJNA662018, and the TCGA-Bladder urothelial carcinoma (BLCA) cohorts are integrated to identify their relationships. A scoring system is constructed according to RBPs gene expression and patients’ survival. A network is constructed to analyze the alternative splicing events and RBP genes. Results A scoring system identified 321 RBPs significantly associated with the prognosis of patients. Subsequent typing of these RBP genes in two single-cell datasets demonstrated that most of the RBP genes had variable copy numbers. Three RBP clusters were identified. Using RBP genes as a signature in BC epithelial cells allows for differentiation between different grades of BC samples. The novel RBP genes-based subtype system reflects BC clinical staging. Notably, CellChat analysis revealed that the RBP genes-associated cell subtypes of T cells had extensive interactions with epithelial cells. Further analysis showed that the ligand-receptor pair MIF-CXCR4 mediated the communication between RBP-associated subtypes of BC epithelial cells and T cells. Conclusions Taken together, RBP genes are associated with BC progress and offer new indicators for precision medicine in BC.

Apigenin 7-glucoside (A7G) can suppress cell proliferation and trigger apoptosis in cervical cancer cells. Considering that hypoxia is associated with the malignant phenotypes in cervical cancer, this study aimed to uncover whether A7G exhibits suppressive effects on the hypoxia-induced malignant phenotype of cervical cancer cells (HeLa cells). Compared to normoxia, hypoxia can enhance the malignant phenotypes of HeLa cells, including cell proliferation, reduced sensitivity against chemotherapeutic agents (oxaliplatin and paclitaxel), cancer stemness, migration, and invasion. A7G intervention (20, 40, and 60 mu M) could impair these malignant phenotypes of HeLa cells and upregulate the expression level of total and nuclear p16 proteins. Molecular docking analysis showed the interaction between anion exchanger 1 and A7G. In p16-silencing HeLa cells, the anticancer effects of A7G were absent. Therefore, hypoxia derives malignant phenotypes of HeLa cells, which could be impeded by A7G in a p16-dependent manner.

To investigate the impact of four single nucleotide polymorphisms (SNPs) of the HIF1α gene and its interaction with Helicobacter pylori (H. pylori) infection on susceptibility to gastric cancer (GC). Logistic regression was used to test the relationship between four SNPs of HIF1α gene and the susceptibility of GC. A generalized multifactor dimensionality reduction (GMDR) model was used to assess the HIF1α gene-H. pylori infection interaction. Logistic regression analysis indicated that both the rs11549465-CT genotype and the T allele were associated with an increased risk of GC, adjusted OR (95

Abstract Highland barley was used as raw material to prepare slow-digested starch by double-enzyme enzymatic hydrolysis process. The non-targeted metabolomics method was used to analyze the correlation between the differences in metabolites of small molecules before and after double-enzyme enzymatic hydrolysis, and to explore the effect on the metabolism of highland barley starch after double-enzyme enzymatic hydrolysis. UHPLC-QTOF-MS detection showed that the main up-regulated metabolites and metabolic pathways in enzymolysis group were mainly flavonoids, and the main down-regulated metabolites and metabolic pathways were mainly lipid metabolism. The results showed that compared with the control group, the enzymatic hydrolysis group regulated the content of sugars and flavonoids in the enzymatic hydrolysis starch by affecting the metabolic pathways such as glycolysis and flavonoid production, thereby affecting the starch characteristics of the double enzyme enzymatic hydrolysis of highland barley flour and making it produce a more gentle blood glucose response in the human body.

Gastric cancer (GC) remains the third leading cause of cancer-related mortality in the world, and ninety-five percent of GC are stomach adenocarcinomas (STAD). The active ingredients of Croci Stigma, such as Isorhamnetin, Crocin, Crocetin and Kaempferol, all have antitumor activity. However, their chemical and pharmacological profiles remain to be elusive. In this study, network pharmacology was used to characterize the action mechanism of Croci Stigma. All compounds were obtained from the traditional Chinese medicine systems pharmacology (TCMSP) database, and active ingredients were selected by their oral bioavailability and drug-likeness index. The targets of Croci Stigma active ingredients were obtained from the traditional Chinese medicine integrated database (TCMID), whereas the related genes of STAD were obtained from DisGeNET platform. Cytoscape was used to undertake visual analyses of the Drug Ingredients–Gene Symbols–Disease (I–G–D) network, and 2 core genes including MAPK14, ERBB3 were obtained, which are the predicted targets of isorhamnetin (IH) and quercetin, respectively. Data analysis from TCGA platform showed that MAPK14 and ERBB3 all upregulated in STAD patients, but only the effect of MAPK14 expression on STAD patients’ survival was significant. Molecular docking showed that IH might affect the function of MAPK14 protein, and then the underlying action mechanisms of IH on STAD were experimentally validated using human gastric cancer cell line, HGC-27 cells. The results showed that IH can inhibit cell proliferation, migration, clonal formation, and arrest cell cycle, but promote the apoptosis of HGC-27 cells. qRT-PCR data demonstrated that IH downregulated the MAPK14 mRNA expression and EMT related genes. WB results showed that IH regulates MAPK/mTOR signaling pathway. These findings suggest that IH has the therapeutic potential for the treatment of STAD.

ObjectiveTo investigate the function of tropomyosin 4 (TPM4) using pan-cancer data, especially in gastric cancer (GC), using comprehensive bioinformatics analysis and molecular experiments.MethodsWe used UCSC Xena, The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), TIMER2.0, GEPIA, cBioPortal, Xiantao tool, and UALCAN websites and databases for the extraction of pan-cancer data on TPM4. TPM4 expression was investigated with respect to prognosis, genetic alterations, epigenetic alterations, and immune infiltration. RNA22, miRWalk, miRDB, Starbase 2.0, and Cytoscape were used for identifying and constructing the regulatory networks of lncRNAs, miRNAs, and TPM4 in GC. Data from GSCALite, drug bank databases, and Connectivity Map (CMap) were used to analyze the sensitivity of drugs dependent on TPM4 expression. Gene Ontology (GO), enrichment analyses of the Kyoto Encyclopedia of Genes and Genomes (KEGG), wound healing assays, and (Matrigel) transwell experiments were used to investigate the biological functions of TPM4 in GC.ResultThe findings of the comprehensive pan-cancer analysis revealed that TPM4 has a certain diagnostic and prognosis value in most cancers. Alterations in the expression of TPM4, including duplications and deep mutations, and epigenetic alterations revealed that TPM4 expression is related to the expression of DNA methylation inhibitors and RNA methylation regulators at high concentrations. Besides, TPM4 expression was found to correlate with immune cell infiltration, immune checkpoint (ICP) gene expression, the tumor mutational burden (TMB), and microsatellite instability (MSI). Neoantigens (NEO) were also found to influence its response to immunotherapy. A lncRNA-miRNA -TPM4 network was found to regulate GC development and progression. TPM4 expression was related to docetaxel,5-fluorouracil, and eight small molecular targeted drugs sensitivity. Gene function enrichment analyses revealed that genes that were co-expressed with TPM4 were enriched within the extracellular matrix (ECM)-related pathways. Wound-healing and (Matrigel) transwell assays revealed that TPM4 promotes cell migration and invasion. TPM4, as an oncogene, plays a biological role, perhaps via ECM remodeling in GC.ConclusionsTPM4 is a prospective marker for the diagnosis, treatment outcome, immunology, chemotherapy, and small molecular drugs targeted for pan-cancer treatment, including GC treatment. The lncRNA-miRNA-TPM4network regulates the mechanism underlying GC progression. TPM4 may facilitate the invasion and migration of GC cells, possibly through ECM remodeling.

Metabolic skeletal disorders remain a major clinical challenge. The complexity of this disease requires a strategy to address the net effects of both inflammation and impaired bone formation. microRNA-based gene therapy provides several therapeutic advantages totackle these issues. Herein, we describe a microRNA-21 (miR-21) delivery system with an additional therapeutic effect from that of the delivery carrier itself. Poly (salicylic acid) (PSA) is, for the first time, synthesized viapolycondensation of salicylic acid (SA), a bioactive ingredient widely used for anti-inflammation in medicine. PSA can self-assemble into nanoparticles (PSA-NPs) and can effectively deliver genes both in vitro and in vivo. The carrier was then attached to repetitive sequences of aspartate, serine, serine (DSS)6 for delivering miRNAs specifically to bone-formation surfaces. In vitro studies showed that miR-21@PSA-NP could effectively realize the intracellular delivery of miR-21 with low toxicity, while in vivo results indicated that the miR-21@PSA-NP-DSS6 prolonged blood circulation time, enhanced bone accumulation, and significantly improved the efficacy of miR-21-based bone anabolic therapy in osteoporotic mice. The constructed delivery system (miR-21@PSA-NP-DSS6) inherited the advantages of both SA and miR-21, which could ameliorate bone-inflamed niche and rescued the impaired bone formation ability. The synergy of anti-inflammatory and pro-osteogenic effects significantly improved trabecular bone microstructure in osteoporotic mice.

Cold and hypoxia are critical drivers of adaptation to high altitudes. Organisms at high altitudes have adapted to maximize the efficiency of oxygen utilization and are less prone to obesity and diabetes than those at low altitudes. Brown adipose tissue (BAT) dissipates energy in the form of heat in both humans and rodents; it also serves to regulate metabolism to curb obesity. However, the role of BAT in high-altitude populations is poorly understood. Serum exosomes can be easily obtained, enabling the study of BAT functions and identification of biomarkers in serum exosomes, both of which contribute to understanding the role of BAT in high-altitude populations. 18 F-Fluorodeoxyglucose ( 18 F-FDG) positron emission tomography integrated with computed tomography (PET/CT) is the gold standard for studying BAT in human adults. Here, we studied BAT in healthy high-altitude populations via PET/CT and serum exosomal microRNAs (miRNAs). The observations were validated in mouse tissues and demonstrated that high-altitude hypoxia activated BAT through attenuated white adipose tissue (WAT) secreted exosomal miR-210/92a, which enhanced the FGFR-1 expression in BAT.

With 5 rice varieties (Yifeng 3321, Yifeng 3315, Yifeng 3317, Yifeng 45, Yifeng 14-24) as the experimental objects, the aseptic seedling method was used to culture the rice seeds, and the HPLC was used to determine the content of amino acids in aseptic rice seedlings as well as the total content of 8 kinds of essential amino acids and the content of protein. And the content of protein and amino acids in the polished rice of 5 varieties was detected, and the analysis of variance was performed for screening of the varieties containing high essential amino acids. The rice with high essential amino acids could be produced to meet peopleu0027s rice quality requirements. The analysis of variance indicated that there were significant differences (F=39.262, p=0.01) in the content of essential amino acids among 5 kinds of rice varieties. By the Duncanu0027s multiple comparison, the differences among rice varieties were calculated to obtain screening results. The aseptic seedlings: Yifeng 3321 (7.268), Yifeng 3315 (6.395), Yifeng 3317 (5.698), Yifeng 45 (5.567), Yifeng 14-24 (5.190). Rice: Yifeng 3321 (2.998), Yifeng 14-24 (2.627), Yifeng 3317 (2.611), Yifeng 3315 (2.503), Yifeng 45 (2.281). Based on the estimated human daily requirement of essential amino acids and amino acids requirement pattern, it was found that the polished rice of 5 varieties was up to standard. The variety with the highest content of essential amino acids was Yifeng 3317 (3830 mg/100g), followed by Yifeng 3321 (3770 mg/100 g). The results showed that the high quality rice variety in this experiment was Yifeng 3321.

Objective: The incidence of gastric cancer is high in Chinese Tibetan. This study aimed to identify the differentially expressed microRNAs (miRNAs) and further explore their potential roles in Tibetan with gastric cancer so as to predict potential therapeutic targets.Methods: A total of 10 Tibetan patients (male: female = 6: 4) with gastric cancer were enrolled for isolation of matched gastric cancer and adjacent non-cancerous tissue samples. Affymetrix GeneChip microRNA 3.0 Array was employed for detection of miRNA expression in samples. Differential expression analysis between two sample groups was analyzed using Limma package. Then, MultiMiR package was used to predict targets for miRNAs. Following, the target genes were put into DAVID (Database for Annotation, Visualization and Integrated Discovery) to identify the significant pathways of miRNAs.Results: Using Limma package in R, a total of 27 differentially expressed miRNAs were screened out in gastric cancer, including 25 down-regulated (e.g. hsa-miR-148a-3p, hsa-miR-148b-3p and hsa-miR-363-3p) and 2 up-regulated miRNAs. According to multiMiR package, a number of 1445 target genes (e.g. Wnt1, KLF4 and S1PR1) of 13 differentially expressed miRNAs were screened out. Among those miRNAs, hsa-miR-148a-3p, hsa-miR-148b-3p and hsa-miR-363-3p were identified with the most target genes. Furthermore, three miRNAs were significantly enriched in numerous common cancer-related pathways, including "Wnt signaling pathway", "MAPK signaling pathway" and "Jak-STAT signaling pathway".Conclusions: The present study identified a downregulation and enrichment in cancer-related pathways of hsa-miR148a-3p, hsa-miR-148b-3p and hsa-miR-363-3p in Tibetan with gastric cancer, which can be suggested as therapeutic targets.

The highest risk areas of gastric cancer are currently Japan, Korea and China; Qinghai, a high-altitude area, has one of the highest gastric cancer rates in China. The incidence of gastric cancer is higher in the Tibetan ethnic group compared to that in the Han ethnic group in Qinghai. This study was conducted to determine the clinical characteristics of mitochondrial DNA (mtDNA) mutations and copy numbers among Tibetans with gastric cancer residing at high altitudes and investigate the association between adaptations to hypoxic conditions and oncogenesis. A total of 23 Tibetan gastric cancer patients and 40 matched controls were recruited in this study. Leukocyte mtDNA genes and copy numbers were analyzed. The haplogroups were classified based on mitochondrial gene sequences. A total of 56.5% of the study participants had used alcohol at some point in their lives and 73.9% were positive for Helicobacter pylori (H. pylori). Eight mutations in 8 mitochondrial genes were identified in 43.4% of the Tibetan cancer patient group. There were no significant differences in leukocyte mtDNA copy number levels based on smoking status, alchohol consumption, obesity or H. pylori infection between the control and cancer groups. Statistical differences were also not found between gastric cancer patients with and those without mtDNA mutations. The majority of Tibetan patients with gastric cancer belonged to the mitochondrial haplogroup M9. In conclusion, Tibetans with gastric cancer residing at high altitudes exhibited a wide spectrum of mtDNA mutations. However, leukocyte mtDNA copy numbers in stage II gastric cancer were not statistically different compared to those in healthy Tibetans.