Inner Mongolia Medical University

Colorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality. Although Synaptotagmin 8 (SYT8) has been implicated in tumorigenesis, its role in CRC is poorly understood. Transcriptomic and clinical data from TCGA and five GEO datasets were analyzed, and survival analysis together with nomogram modeling was applied to evaluate the prognostic value of SYT8. Functional enrichment and immune infiltration analyses were performed to investigate its potential roles and its impact on the tumor microenvironment. SYT8 expression in CRC and adjacent normal tissues was validated by qRT-PCR and western blotting. Knocking down experiments in vitro were conducted to assess its effects on cell proliferation, migration, and related signaling pathways. Compared to normal samples, SYT8 was significantly highly expressed in CRC tissues. Additionally, elevated SYT8 expression was strongly associated with poorer overall survival and identified as an independent prognostic factor. Functional enrichment analysis indicated its potential involvement in multiple signaling pathways, including MAPK and PI3K-Akt. Immune-related analyses revealed that tumors with high SYT8 expression exhibited increased Treg infiltration and upregulation of immune checkpoint molecules PDCD1 and LAG3. Significantly, downregulation of SYT8 suppressed HT29 cell viability, proliferation, and migration. Moreover, SYT8 downregulation notably reduced the phosphorylation of Akt and ERK1/2 in HT29 cells. SYT8 plays a critical role in the development and progression of CRC and holds potential as a prognostic biomarker, as well as a novel therapeutic target.

To investigate the relationship among the along perivascular space (ALPS) index, conventional neuroimaging markers, and cognitive impairment in patients with relapsing–remitting multiple sclerosis (RRMS). This study included 45 RRMS patients and 41 healthy controls (HC). All participants underwent clinical evaluation, magnetic resonance imaging (MRI), and comprehensive cognitive assessments. Cognitive function was assessed using the Brief International Cognitive Assessment for MS (BICAMS), which includes the Symbol Digit Modalities Test (SDMT), California Verbal Learning Test–II (CVLT-II), and Brief Visuospatial Memory Test–Revised (BVMT-R). Additional tests evaluated attention, executive function, verbal fluency, and global cognition. Cognitive impairment was defined as a Z‑score ≤ -1.5 in at least two of the three BICAMS domains. Spearman correlation and multiple linear regression analyses were used to examine associations between neuroimaging metrics and cognitive scores in RRMS patients. Backward stepwise logistic regression was performed to identify variables independently associated with cognitive impairment. RRMS patients had a significantly lower ALPS index compared to HC (t = -2.225, q = 0.029). Within the RRMS group, patients with cognitive impairment showed further reductions in the ALPS index. Multiple linear regression confirmed that the ALPS index was significantly associated with Z‑scores of the Symbol Digit Modalities Test (SDMT; β = 0.415, q = 0.003), PASAT-3 s (Paced Auditory Serial Addition Test-3 s; β = 0.305, q = 0.037), PASAT-2 s (β = 0.429, q = 0.002) and Controlled Oral Word Association Test (COWA; β = 0.305, q = 0.044). In addition, a negative correlation was observed between white matter lesion number (WMLN) and the Z‑scores of COWA (β = -0.340, q = 0.013). In the backward stepwise logistic regression model, the ALPS index (OR = 0.044, 95% CI: 0.003–0.776, q = 0.033) and normalized white matter volume (nWMV; OR = 0.764, 95% CI: 0.599–0.975, q = 0.030) were retained as variables independently associated with cognitive impairment. Our study suggests that both a reduced ALPS index and lower nWMV are independently associated with cognitive impairment in RRMS. These findings implicate the combined roles of impaired interstitial fluid clearance and structural integrity in RRMS-related cognitive dysfunction. As a non-invasive MR metric, the ALPS index may serve as a potential complementary biomarker for assessing cognitive risk in RRMS.

Knowledge of the mechanisms through which common single-nucleotide polymorphisms (SNPs) modulate colorectal cancer (CRC) susceptibility is central to elucidating the molecular basis of this disease. Genome-wide association studies (GWAS) reveal noncoding SNPs influencing CRC susceptibility, yet their functional mechanisms, particularly through gene expression dysregulation, DNA methylation alterations, and interactions with gut microbiota, remain uncharacterized. Through integrative analysis, systematically exploring the effects of genetic variations on gene expression heterogeneity, DNA methylation, and gut microbiome is expected to yield potential biomarkers for early diagnosis and intervention of CRC. An integrative framework is developed to prioritize causal risk genes at CRC-associated GWAS loci, applying the SMR&HEIDI (Summary-data-based Mendelian randomization and heterogeneity in dependent instruments) and TSMR (Two-sample Mendelian Randomisation) methods. The findings were validated via gene expression and TF binding affinity. 10 tissue-specific gene-SNP pairs, 3 blood eQTL-gene pairs, 26 gene-CpG-SNP regulatory modules, and 39 microbiota-associated gene-SNP pairs are identified. A few potential regulatory influences on CRC development associated with genes and variants, such as POU5F1B and rs10797801, were identified. Moreover, the genetic variants disrupted TF binding affinity while only a few promoted the binding of transcription factors (TFs). The data integration enabled us to prioritize genes according to different regulatory mechanisms, such as gene expression and DNA methylation, and bridge the gap between statistical associations and biological functionality. Multi-omics integration reveals some causal risk genes and variants implicated in CRC. These findings offer novel insight into the molecular mechanisms underlying CRC susceptibility and provide valuable clues for diagnosis and therapeutic intervention strategies.

Patients with peripheral T cell lymphoma (PTCL) who achieved tumor response with first-line standard therapy were at high risk of disease relapse. We explored golidocitinib (150 mg once daily) as maintenance therapy for this group of patients (JACKPOT26, NCT06511869). This study included two cohorts: patients achieving a complete response (Cohort 1 (CR), N = 30) and a partial response (Cohort 2 (PR), N = 18) during induction stage. All enrolled patients were transplant ineligible or did not have a transplant plan. All dosed patients were included in the efficacy and safety analysis. In Cohort 1, the 24-month disease free survival (DFS) rate was 74.2% with golidocitinib treatment. In nodal subtypes (AITL, NOS, ALK- ALCL), the 24-month DFS rate was 62.7%. In Cohort 2, median progression free survival (PFS) was 17.4 months, and 24-month PFS rate was 48.6%. Nine out of 18 patients with initial PR achieved complete response, leading to a complete response rate of 50.0%, and median duration of response of 23.9 months. The most common ≥grade 3 treatment-related treatment-emergent adverse events (TRAEs) were hematological adverse events in nature, including neutrophil count decreased (47.9%), white blood cell count decreased (31.3%), lymphocyte count decreased (14.6%) and leukopenia (12.5%). The majority of these TRAEs were reversible and clinically manageable. TRAEs leading to treatment interruption and discontinuation occurred in 60.4% and 10% of patients, respectively. No TRAEs leading to fatal outcomes were reported. This study suggests the potential of golidocitinib as maintenance therapy for patients with PTCL.

To compare the clinical efficacy of all-inside reconstruction and traditional reconstruction in treating anterior cruciate ligament (ACL) injuries under knee arthroscopy. A total of 100 patients with ACL injuries admitted to the Affiliated Hospital of Inner Mongolia Medical University from January 2024 to December 2024 were prospectively enrolled and randomly divided into the all-inside reconstruction group (n = 50) and the traditional reconstruction group (n = 50) using the Random Number Table Method. Graft size, Tegner, IKDC, Lysholm scores, and VAS scores of both groups prior to surgery and at 3, 6, and 12 months postoperatively were compared, and the return-to-sport conditions at 1 year postoperatively were evaluated. The measurement data were analyzed by the independent samples t-test, and the categorical data were analyzed by the chi-square test, with P value < 0.05 considered statistically significant. The baseline data of the two groups were balanced (all P > 0.05). The graft length in the all-inside group was significantly shorter than that in the other (6.60 ± 0.42 cm vs. 8.10 ± 0.45 cm, P < 0.001), while there was no significant difference in diameter (P = 0.339). At each time point postoperatively, the Tegner, IKDC, and Lysholm scores of both groups were significantly improved, with no clinically significant difference between (the difference in Lysholm score at 12 months after surgery was 2.24 points, P = 0.032, but lower than MCID). The VAS score of the all-inside group at 12 months postoperatively was significantly lower (0.24 ± 0.12 vs. 0.87 ± 0.11, P < 0.001). In addition, at 1 year postoperative, the return-to-sport rate of this group was 64.0% (32/50), significantly higher than that of the other (42.0%, 21/50) (P < 0.05). All-inside ACL reconstruction can significantly shorten the required graft length, relieve long-term pain, and increase the return-to-sport rate while ensuring the effect of knee joint function recover. It is thus proved to be a safe and effective surgical method.

The prognosis for hepatocellular carcinoma remains grim. Combining radiotherapy with immune checkpoint blockade (ICB) has shown potential to enhance therapeutic outcomes, yet there is a pressing need for further advancements. Our previous research demonstrated that this combined approach suppresses ALKBH5 gene expression and increases m6A modification levels in hepatocellular carcinoma tissues. High-throughput sequencing and detailed molecular analysis revealed that inhibiting ALKBH5 amplifies CIITA m6A modifications post-therapy. This modulation triggers MHC II molecule expression in tumors, facilitating the presentation of tumor-associated antigens to CD4 + T lymphocytes and the recruitment of CD8 + T cells for an anti-tumor immune response. Building on these findings, we engineered a CIITA vector with a specific site mutation to confirm that the regulation of CIITA by the combined radiotherapy and immunotherapy is mediated through m6A methylation. Consequently, we established a comprehensive network involving ALKBH5, CIITA, MHC II, and CD4+ and CD8 + T cells. To elucidate the role and underlying molecular mechanisms of this combined therapy in reshaping the tumor immune microenvironment for hepatocellular carcinoma, we employed multi-omics approaches across in vitro, animal model, and clinical multi-dimensional studies, offering novel insights for enhancing treatment efficacy.

Brucella outer membrane proteins (Omps) are an important part of its cell wall and major virulence-related factors. Omp16 and Omp19 proteins are the advantageous antigens of Brucella and have been widely used in research on vaccines against brucellosis. As an emerging vaccine, the mRNA vaccine has unique advantages in the fight against intracellular parasitic bacteria. In this study, mRNA encoding the omp16 and omp19 genes of Brucella. melitensis (B. melitensis) was synthesized using in vitro transcription. The target mRNA was transfected into HEK 293T cells to evaluate protein expression levels and assess its immunogenicity. Finally, bioinformatic approaches were employed to analyze potential antigenic epitopes. In this study, the successfully constructed recombinant plasmids pIVTRup-omp16 and pIVTRup-omp19 were utilized to synthesize omp16-mRNA and omp19-mRNA, each approximately 600 nt in length. Western blot analysis detected the expression of proteins with molecular weights of 16 kDa and 19 kDa in HEK 293T cells at 24 h post-transfection with mRNA. Purified rOmp16 and rOmp19 had good immunogenicity, which could specifically bind to serum antibodies of brucellosis patients. rOmp16 had stronger immunogenicity than rOmp19. Epitope prediction showed that Omp16 contained seven epitopes and Omp19 contained six epitopes. In addition, Omp16 and Omp19 could form stable complexes with target receptors. Simulated immunization with Omp16 and Omp19 proteins significantly activated both CD4+ and CD8+ T cells. The immunogenic proteins were successfully expressed in cells based on the mRNA fragments synthesized from omp16 and omp19 genes of B. melitensis, which was a preliminary exploration for the preparation of B. melitensis mRNA vaccine.