TARDBP is a candidate diagnostic biomarker promoting tumor progression via impacting tumor immunity and tumor microenvironment.

In the realm of cancer research, particularly hepatocellular carcinoma (HCC), TAR DNA-binding protein (TARDBP) has transitioned from being associated with neurodegenerative diseases to emerging as a significant molecule in oncology due to its aberrant expression in HCC and other malignancies. This shift underlines the versatility of TARDBP and its critical role in tumorigenesis. Our study illuminates TARDBP's universal upregulation across various cancers, indicating its involvement in fundamental oncogenic processes and potential impact on genomic instability. The relationship between TARDBP expression and tumor mutational burden (TMB) across several cancers highlights its influence on a key hallmark of cancer progression. Additionally, TARDBP's interaction with immune and inflammatory factors within the tumor microenvironment, including its association with immune-stimulatory factors and inverse relationship with immune inhibitors, suggests its role in modulating immune evasion. Clinically, TARDBP's aberrant expression correlates with adverse patient outcomes in HCC, making it a promising candidate for therapeutic targeting. The study concludes that TARDBP holds significant potential as a novel therapeutic target in HCC and possibly other malignancies, meriting further exploration to integrate TARDBP-targeted therapies into cancer treatment protocols, thereby advancing the field of precision medicine.

Stapled transperineal rectovaginal fistula repair for low- and mid-level rectovaginal fistulas: A comparison study with rectal mucosal advancement flap repair.

BACKGROUND: As an innovative treatment, stapled transperineal rectovaginal fistula repair (STR) for rectovaginal fistula (RVF) has demonstrated effectiveness in preliminary reports. This study aims to compare STR with rectal mucosal advancement flap repair (RAF), a widely utilized surgical procedure, for the surgical outcome of the low- and mid-level RVF. METHODS: In this retrospective cohort study, patients with low- and mid-level RVF who underwent STR or RAF were included from both the Sixth Affiliated Hospital of Sun Yat-sen University and Xi'an Daxing Hospital. Among the 99 total patients, 77 underwent STR and 22 underwent RAF. Patient demographics, operative data, and outcomes were collected and analyzed. Recurrence rate and associated risk factors were evaluated. RESULTS: There were no statistically significant differences among patients in terms of clinical characteristics like age, BMI, aetiology, and fistula features. During the follow-up period of 20 months (interquartile range 3.0-41.8 months), a total of 28 patients relapsed, with a significantly lower recurrence rate in the STR group (20.8 %) than in the RAF group (54.6 %) (P = 0.005). In the multivariate Cox analysis, STR was an independent protective factor against recurrence (HR: 0.37, 95%CI: 0.17-0.79, P = 0.01). Logistic regression indicated that there was no statistically significant difference between these two procedures in terms of surgical complications (OR: 0.53, 95%CI: 0.19-1.48, P = 0.23). CONCLUSION: For low- and mid-level RVF, STR may be an alternative option for treatment modality that offers a lower recurrence rate, without observed disadvantage in terms of surgical complication rates.

Association between Dietary Inflammatory Index and Risk of Colorectal Adenomatous Polyps in Kashgar Prefecture of Xinjiang, China.

Malignant colorectal tumors and precancerous lesions are closely associated with chronic inflammation. Specific dietary patterns can increase chronic inflammation in the body, thereby promoting the occurrence of tumors and precancerous lesions. We have conducted a case-control study in Kashgar Prefecture, Xinjiang, China, to explore the association between the energy-adjusted dietary inflammatory index (E-DII) and the risk of colorectal adenomatous polyps (CAP). A total of 52 newly diagnosed patients with CAP and 192 controls at the First People's Hospital of Kashgar Prefecture were enrolled in this study. Dietary information was collected using a food frequency questionnaire. The E-DII was calculated based on dietary data, reflecting an individual's dietary inflammatory potential. Logistic regression models were used to evaluate the relationship between the E-DII and the risk of CAP, with adjustments for potential confounding factors. The results showed that the maximum anti- and pro-inflammatory values of E-DII were -4.33 and +3.48, respectively. Higher E-DII scores were associated with an increased risk of CAP, and this association remained statistically significant after adjusting for age, sex, body mass index, smoking status, and other relevant variables. Notably, a more pro-inflammatory dietary pattern may be related to an increased risk of developing CAP in Kashgar Prefecture.

Single-Cell RNA Sequencing Reveals Heterogeneity in the Tumor Microenvironment between Young-Onset and Old-Onset Colorectal Cancer.

BACKGROUND: The incidence of sporadic young-onset colorectal cancer (yCRC) is increasing. Compared with old-onset colorectal cancer (oCRC), yCRC has different clinical and molecular characteristics. However, the difference in the tumor microenvironment (TME) between yCRC and oCRC remains unclear. METHODS: Fourteen untreated CRC tumor samples were subjected to single-cell RNA sequencing analysis. RESULTS: B cells and naïve T cells are enriched in yCRC, while effector T cells and plasma cells are enriched in oCRC. Effector T cells of yCRC show decreased interferon-gamma response and proliferative activity; meanwhile, Treg cells in yCRC show stronger oxidative phosphorylation and TGF-ß signaling than that in oCRC. The down-regulated immune response of T cells in yCRC may be regulated by immune and malignant cells, as we observed a downregulation of antigen presentation and immune activations in B cells, dendritic cells, and macrophages. Finally, we identified malignant cells in yCRC and oCRC with high heterogeneity and revealed their interactions with immune cells in the TME. CONCLUSIONS: Our data reveal significant differences of TME between yCRC and oCRC, of which the TME of yCRC is more immunosuppressive than oCRC. Malignant cells play an essential role in the formation of the suppressive tumor immune microenvironment.

Current strategies for SARS-CoV-2 molecular detection.

The molecular detection of SARS-CoV-2 is extremely important for the discovery and prevention of pandemic dissemination. Because SARS-CoV-2 is not always present in the samples that can be collected, the sample chosen for testing has inevitably become the key to the SARS-CoV-2 positive cases screening. The nucleotide amplification strategy mainly includes Q-PCR assays and isothermal amplification assays. The Q-PCR assay is the most used SARS-CoV-2 detection assay. Due to heavy expenditures and other drawbacks, isothermal amplification cannot replace the dominant position of the Q-PCR assay. The antibody-based detection combined with Q-PCR can help to find more positive cases than only using nucleotide amplification-based assays. Pooled testing based on Q-PCR significantly increases efficiency and reduces the cost of massive-scale screening. The endless stream of variants emerging across the world poses a great challenge to SARS-CoV-2 molecular detection. The multi-target assays and several other strategies have proved to be efficient in the detection of mutated SARS-CoV-2 variants. Further research work should concentrate on: (1) identifying more ideal sample plucking strategies, (2) ameliorating the Q-PCR primer and probes targeted toward mutated SARS-CoV-2 variants, (3) exploring more economical and precise isothermal amplification assays, and (4) developing more advanced strategies for antibody/antigen or engineered antibodies to ameliorate the antibody/antigen-based strategy.

Gastric Mucosa Pathology in Rats with Precancerous Lesions of Gastric Cancer with Spleen Deficiency and Blood Stasis.

Objective: This research aimed at better understanding the histopathological development of precancerous lesions of gastric cancer (PLGC) and organelle ultrastructure changes. Methods: Sprague-Dawley rats were randomly assigned to the model and control groups. Model rats drank N-methyl-N'-nitro-N-nitrosoguanidine solution, while control rats drank pure water ad libitum. At 1, 3, 5, 6, and 8 months after the start of feeding, eight rats were randomly chosen from each group, and gastric mucosa tissues were removed for histopathological analysis. H&E staining was applied to analyze the pathological histological structure of the rat gastric mucosa via a light microscope, and the ultrastructural changes were observed via a transmission electron microscope. Results: Gastric mucosal pathologies of model rats such as mucosal atrophy, intestinal metaplasia, inflammatory lesions, and even intraepithelial neoplasia deteriorated over time. The endoplasmic reticulum gap widened, the mitochondrial endothelial cristae were disrupted, the nuclear membrane thickened, and chromatin condensed with heterotypic alterations in the main and parietal cells. Additionally, endothelial cell enlargement and thickening of the microvascular intima were seen. Conclusion: Our research showed that the PLGC progression of rats is correlated with the pathological alteration axis of "normal gastric mucosa-gastric mucosa inflammatory changes-intestinal metaplasia with mild dysplasia-moderate to severe dysplasia." Ultrastructure analysis of model rats is compatible with the structural changes in the gastric mucosa with spleen deficiency and blood stasis. The pathological evolutionary axis and ultrastructural analysis are helpful for evaluating potential novel herbal therapies for PLGC.