Bo Wei

Background: Oral antibiotics (OA) combined with mechanical bowel preparation (MBP) significantly decrease the rate of surgical site infections (SSIs). However, the prophylactic effects in region-specific colorectal surgery have not been assessed. Materials and methods: A single-centre, single-blind, randomized controlled trial was conducted from 2019 to 2022. Patients were eligible if they were diagnosed with nonmetastatic colorectal malignancy, and laparoscopic colorectal surgery was indicated. Participants were randomly assigned (1:1) to the experimental (OA+MBP preparation) or control group (MBP preparation). The randomization was further stratified by resected region. The primary outcome was the incidence of SSIs. Patients were followed up for 1 month postoperatively, and all complications were recorded. Result: Between 2019 and 2022, 157 and 152 patients were assigned to the experimental and control groups, respectively, after 51 patients were excluded. The incidence of SSIs in the control group (27/152) was significantly higher than that in the experimental group (13/157; P=0.013), as was the incidence of superficial SSIs (5/157 vs. 14/152, P=0.027) and deep SSIs (7/157 vs. 16/152, P=0.042). After redistribution according to the resected region, the incidence of SSIs was significantly higher in the control group with left-sided colorectal resection (descending, sigmoid colon, and rectum) (9/115 vs. 20/111, P=0.022) but was similar between the groups with right-sided colon resection (ascending colon) (3/37 vs. 7/36, P=0.286). No differences were noted between the groups in terms of other perioperative complications. Conclusion: OA+MBP before colorectal surgery significantly reduced the incidence of SSIs. Such a prophylactic effect was particularly significant for left-sided resection. This preparation mode should be routinely adopted before elective left-region colorectal surgeries.

Background: Biomarkers based on immune context may guide prognosis prediction. T-cell inactivation, exclusion, or dysfunction could cause unfavorable tumor microenvironments, which affect immunotherapy and prognosis. However, none of the immuno-biomarkers reported to date can differentiate colorectal-cancer (CRC) patients. Thus, we aimed to classify CRC patients according to the levels of T-cell activation, exclusion, and dysfunction in the tumor microenvironment.Methods: RNAseq data of 618 CRC patients from The Cancer Genome Atlas and microarray data of 316 CRC patients from Gene Expression Omnibus were analysed using the Tumor Immune Dysfunction and Exclusion algorithm. Unsupervised clustering was used to classify patients.Results: Based on the expression signatures of myeloid-derived suppressor cells, cancer-associated fibroblasts, M2-like tumor-associated macrophages, cytotoxic T-lymphocytes, and PD-L1, all patients were clustered into four subtypes: cluster 1 had a high level of immune dysfunction, cluster 2 had a low level of immune activation, cluster 3 had intense immune exclusion, and cluster 4 had a high level of immune activation and a moderate level of both dysfunction and exclusion signatures. Compared with cluster 1, the hazard ratios and 95% confidential intervals for overall survival were 0.63 (0.35–1.13) for cluster 2, 0.55 (0.29–1.03) for cluster 3, and 0.30 (0.14–0.64) for cluster 4 in multivariate Cox regression. Similar immune clustering and prognosis patterns were obtained upon validation in the GSE39582 cohort. In subgroup analysis, immune clustering was significantly associated with overall survival among stage I/II patients, microsatellite stable/instability-low patients, and patients not treated with adjuvant therapy.Conclusions: Our findings demonstrated that classifying CRC patients into different immune subtypes serves as a reliable prognosis predictor and may help to refine patient selection for personalized cancer immunotherapy.

At present, cancer is the first cause of death for humans, but early detection and treatment can help improve prognoses and reduce mortality. However, further development of carrier-assistant drug delivery systems (DDSs) is retarded by the aspects such as the low drug-carrying capacity, carrier-induced toxicity and immunogenicity, complex synthesis manipulation. The development of nanoscale drug delivery systems (NDDS) have been rapidly developed to address these issues. In this article, we used PLGA-PEG with good biocompatibility to encapsulate Fe₃O₄ nanoparticles (a magnetic resonance imaging contrast agent) and DOX (an antitumour drug) via the emulsion-solvent evaporation method, aimed at achieving a dual function of the early detection and the treatment of mammary cancer. The results showed that the Fe₃O₄/DOX/PLGA-PEG nanoparticles had a relatively uniform size, a high carrier rate of Fe₃O₄ and high encapsulation efficiency of DOX, and a relatively high activity of released DOX within 120 h. In addition, in vitro studies showed that the Fe₃O₄/DOX/PLGA-PEG nanoparticles were cytocompatibility in NIH 3T3 fibroblast cells culture study while had a special effect on destroying human breast cancer MCF-7 cells compared with pure DOX solution. In vitro studies revealed that the Fe₃O₄/DOX/PLGA-PEG enabled enhanced T2 contrast magnetic resonance. Overall, our multifunctional Fe₃O₄/DOX/PLGA-PEG nanoparticles, composed of biocompatible substances and therapeutic/imaging materials, have great potential for the early detection of cancer and accurate drug delivery via the dynamic monitoring using MRI.

N6-methyladenosine (m6A) modification is the most pervasive modification in mRNA, and has been considered as a new layer of epigenetic regulation on mRNA processing, stability and translation. Despite its functional significance in various physiological processes, the role of the m6A modification involved in breast cancer is yet fully understood. We used the m6A-RNA immunoprecipitation sequencing to identify the potential targets in breast cancer. To determine the underlying mechanism for the axis of FTO-BNIP3, we performed a series of in vitro and in vivo assays in 3 breast cancer cell lines and 36 primary breast tumor tissues and 12 adjunct tissues. We showed that FTO, a key m6A demethylase, was up-regulated in human breast cancer. High level of FTO was significantly associated with lower survival rates in patients with breast cancer. FTO promoted breast cancer cell proliferation, colony formation and metastasis in vitro and in vivo. We identified BNIP3, a pro-apoptosis gene, as a downstream target of FTO-mediated m6A modification. Epigenetically, FTO mediated m6A demethylation in the 3’UTR of BNIP3 mRNA and induced its degradation via an YTHDF2 independent mechanism. BNIP3 acts as a tumor suppressor and is negatively correlated with FTO expression in clinical breast cancer patients. BNIP3 dramatically alleviated FTO-dependent tumor growth retardation and metastasis. Our findings demonstrate the functional significance of the m6A modification in breast cancer, and suggest that FTO may serve as a novel potential therapeutic target for breast cancer.

Breast cancer is the most common malignant tumor among women, and the incidence and mortality of breast cancer has rapidly increased in recent years. Studies have indicated that high mobility group A1 (HMGA1), an important member of the HMGA family, plays a role in the pathogenesis and progression of malignant tumors, including breast cancer. This study aims to evaluate the effect of HMGA1 in breast cancer. Interestingly, we found that HMGA1 expression was significantly higher in breast cancer tissues than in adenoma tissues and closely correlated with the clinical stage and histological grade in breast cancer patients. Further study showed that HMGA1 knockdown inhibited the proliferation and migration of breast cancer cells. Thus, the results demonstrated that HMGA1 could act as an independent prognostic indicator in breast cancer. HMGA1 expression was closely correlated with the clinical stage, histological grade, and tumor size in breast cancer patients and breast cancer progression in transgenic MMTV‐PyMT mice. Anat Rec, 301:1061–1067, 2018.

P-selectin, a cell adhesion molecule, is an important member of the selectin family. Recent studies have shown that P-selectin deletion inhibits tumor growth in Rip1-Tag2 mice by suppressing platelet accumulation in tumor tissues. This study aimed to evaluate whether and how P-selectin affects tumor stiffness in Rip1-Tag2 mice. To explore the role of P-selectin in tissue stiffness, we demonstrated that tumor progression in Rip1-Tag2 mice was correlated with tissue stiffness using immunofluorescence and histological staining. Furthermore, we showed that P-selectin deficiency significantly decreased tissue stiffness by inhibiting lysyl oxidase (LOX) expression. Our experiments involving Rip1-Tag2 mice treated with the LOX inhibitor BAPN showed that BAPN significantly abolished collagen deposition to decrease tumor stiffness and thus inhibit tumor growth. These results indicate that P-selectin deletion significantly decreases tumor stiffness in Rip1-Tag2 mice by inhibiting LOX expression. Further study demonstrated that P-selectin-mediated platelet accumulation increases tissue stiffness mainly by increasing LOX expression and thus promotes tumor growth. Therefore, P-selectin may be an effective therapeutic targeting for treating human insulinomas.