Efficacy and safety of aspirin in venous thromboembolism prevention after total hip arthroplasty, total knee arthroplasty or fracture.

Background: This study aims to analyse the efficacy and safety of aspirin in the prevention of venous thromboembolism (VTE) for patients undergoing total hip arthroplasty (THA), total knee arthroplasty (TKA) or fracture. Patients and methods: Two independent investigators searched PubMed, Embase, Cochrane and ClinicalTrials.gov from January 2000 to June 2023 to retrieve randomized control trials (RCTs) about aspirin in VTE prevention after arthroplasty or fracture. Then, the relative risk (RR) was utilized to evaluate its efficiency and safety. Results: A total of 16 RCTs with 27,864 patients were included. There was no statistical difference in the incidence of deep-vein thrombosis (RR: 1.31, p = 0.100), pulmonary embolism (RR:1.05, p = 0.850), VTE (RR:1.28, p = 0.290), major bleeding (RR:0.96, p = 0.900), and death (RR:1.01, p = 0.960) between the aspirin group and the anticoagulants group. Subgroup analysis showed that a relatively higher incidence of deep-vein thrombosis in patients undergoing TKA (RR:1.49, p = 0.030), fracture (RR:1.48, p = 0.001), patients receiving 81 mg aspirin twice daily (RR:1.48, p = 0.001) and patients from North America (RR:1.57, p<0.001) when comparing aspirin with anticoagulants. Meanwhile, the incidence of VTE was higher in patients receiving 100 mg aspirin once daily (RR:1.82, p<0.001) compared with anticoagulants. Additionally, the incidence of all bleeding (RR:2.00, p = 0.030) was higher in patients receiving aspirin in Asia compared with anticoagulants. Conclusions: In terms of clinical effectiveness and safety, aspirin (antiplatelet agent) was generally not inferior to anticoagulants in the prevention of VTE after THA, TKA, or fracture. Notably, the clinical effectiveness of aspirin was affected by different surgical types, the doses of aspirin and races.

Intervention of epithelial mesenchymal transition against colon cancer cell growth and metastasis based on SOX21/POU4F2/Hedgehog signaling axis.

AIMS: Colon cancer poses a major threat to human health and a heavy burden on the national economy. As a member of the SOX transcription factor family, SRY-box transcription factor 21 (SOX21) is associated with various cancers, but its mechanism of action in colon cancer remains unclear. This study focused on the molecular mechanisms of transcription factor SOX21 in proliferation and metastasis of colon cancer cells. MAIN METHODS: We analyzed SOX21 expression level and its impact on survival in colon cancer patients by bioinformatics analysis. We used public databases for gene correlation, GSEA enrichment analysis. Cell function experiments (colony formation assay, wound healing assay, Transwell migration and invasion assay) were utilized to determine the impact of SOX21 silencing and over-expression on cell proliferation and metastasis. The luciferase reporter assay, CUT&RUN-qPCR assay and Methylation Specific PCR were used to explore SOX21-POU class 4 homeobox 2 (POU4F2) molecular interactions. The molecular mechanisms were verified by Quantitative real-time PCR and Western blot analysis. KEY FINDINGS: SOX21 is highly expressed and affects the overall survival of colon cancer patients. SOX21 can attenuates POU4F2 methylation state by binding with it. In addition, this interaction facilitate its transcriptional activation of Hedgehog pathway, mediates epithelial-mesenchymal transition (EMT), consequently promoting the proliferation and metastasis of colon cancer cells. SIGNIFICANCE: Our study reveals that SOX21 is an oncogenic molecule and suggests its regulatory role in colon carcinogenesis and progression, providing new insights into the treatment of this disease.

Association of ankylosing spondylitis with the risk of cancer: a meta- analysis of cohort studies.

OBJECTIVES: The potential impact of ankylosing spondylitis (AS) on cancer risk remains unclear. This study seeks to investigate the relationship between AS and different types of cancers. METHODS: A literature search of the PubMed, Embase and Cochrane Library up to July 10th, 2023, was conducted. Two investigators selected eligible studies and extracted relevant data. The study used the random-effects model to explore the causality between AS and cancer, utilising relative risk (RR) as a measure for the study. RESULTS: A total of 20 cohorts with >330 000 participants were included. The pooling analysis shows AS being associated with a higher risk of cancers (RR = 1.16, 95% CI : 1.07-1.26, p= 0.001, I2=70.60%). In the subgroup analysis, AS has a higher cancer risk in Asia, but this association is not significant in Europe. Individual investigations indicate that AS is associated with an increased risk of bone cancer (RR = 3.41, 95% CI : 1.45-7.99, p= 0.005, I2=0.00%), thyroid gland cancer (RR = 1.76, 95% CI : 1.29-2.40, p< 0.001, I2=13.70%), multiple myeloma (RR = 1.74, 95% CI : 1.42-2.15, p< 0.001, I2=27.20%), leukaemia (RR = 1.52, 95% CI : 1.27-1.82, p< 0.001, I2=0.00%), kidney cancer (RR = 1.45, 95% CI : 1.08-1.94, p= 0.014, I2=0.00%), prostate cancer (RR = 1.43, 95% CI : 1.17-1.74, p< 0.001, I2=82.80%), and non-Hodgkin's lymphoma (RR = 1.42, 95% CI : 1.17-1.73, p< 0.001, I2=0.00%). However, there is no significant correlation with connective tissue cancer, brain cancer, testicular and other male cancers, bladder cancer, female cancers, skin cancer, and cancers of the digestive system and respiratory system. CONCLUSION: AS appears to be related to cancer development. The results highlighted the necessity for large-scale studies, considering influencing factors such as AS course, medication histories, and potential biases when examining cancer risk.

No association between cholecystectomy and risk of colorectal cancer: a meta-analysis of cohort studies.

OBJECTIVE: Cohort studies have reported an association between colorectal cancer and cholecystectomy. However, the conclusions are inconsistent. Thus, this meta-analysis will quantify the risk of colorectal cancer following cholecystectomy. METHODS: PubMed, EMBASE and Cochrane Library databases were searched for relevant cohort studies. The quality of individual observational studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. The relative risk of colorectal cancer after cholecystectomy was calculated using STATA 14.0 software. Subgroup and sensitivity analyses were used to examine the source of heterogeneity. Funnel plots and Egger's test were finally performed to assess the publication bias. RESULTS: This meta-analysis included 14 studies comprising 2,283,616 subjects. Pooled analysis indicated that cholecystectomy was not a risk factor for colorectal cancer (Colorectal: RR 1.06; 95% CI 0.75-1.51, p = 0.739 Colon: RR 1.30; 95% CI 0.88-1.93, p = 0.182 Rectal: RR 0.99; 95% CI 0.74-1.32, p = 0.932). Subgroup showed that patients are at an increased risk of sigmoid colon following cholecystectomy (RR 1.42; 95% CI 1.27-1.58, p = 0.000). Furthermore, it was shown that both females and males undergoing cholecystectomy may have higher risks of colon cancer (Female: RR = 1.47, 95% CI 1.01-2.14, P = 0.042 Male: RR = 1.32; 95% CI 1.07-1.63, P = 0.010), which is similarly observed in the right colon (Female: RR 1.99; 95% CI 1.31-3.03, p = 0.001, P = 0.017 Male: RR 1.68; 95% CI 0.81-3.49, p = 0.166). CONCLUSIONS: No clear evidence to support the association between cholecystectomy and an increased risk of colorectal cancer. For patients with valid indications, timely cholecystectomy could be performed without the risk of colorectal cancer.

Is antibody-drug conjugate a rising star for clinical treatment of solid tumors? A systematic review and meta-analysis.

Antibody-drug conjugates (ADCs) show significant advantages in cancer treatment due to their high selectivity and anti-tumor activity, but the efficacy and safety of the treatment of solid tumors are unknown. We searched research databases, major conference proceedings and trial registries for randomized controlled trials (RCTs). Then, we selected qualified studies and extracted dates. Studies were assessed for quality, and a meta-analysis was conducted to quantify effects of ADCs on overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and adverse events (AEs). The within-study heterogeneity was evaluated by subgroup and sensitivity analysis. Eleven RCTs with 4353 participants were included. ADCs had better PFS (HR: 0.69, 95 % CI: 0.56-0.82) and OS (HR: 0.76, 95 % CI: 0.61-0.92). ADCs resulted in lower risk of febrile neutropenia in blood system. Conversely, ADC therapy had not a prepotent on ORR (RR: 1.36, 95 % CI: 0.71-2.60).

Multimode participation of traditional Chinese medicine in the treatment of COVID-19.

BACKGROUND: The outbreak of COVID-19 has swiftly spread across China and all over the world, resulting in severe contagious pneumonia. However, no specific anti-COVID-19 drugs or methods are available for the treatment of this acute and fatal disease. In recent years, as the efficacy and safety of traditional Chinese medicine (TCM) have been universally acknowledged, it has been brought to a crucial status domestically and overseas for the treatment of COVID-19. METHODS: We searched relevant literature, electronic databases, and official statements, diagnoses and protocols to retrieve studies and applications related to traditional Chinese medicine for COVID-19 in terms of regulations and policies, clinical evidence, preclinical rationale and big data analysis and then summarized the discovery and development of potential drugs and their targets. RESULTS: Clinicians, researchers, governments, the public, colleges, institutes and companies collected and classified associated policies, regulations and actual contributions, searched clinical trials and preclinical experimental outcomes from databases, studied potential TCM drugs with possible mechanisms, retrieved numerous big data analysis method and gathered pooled results of compounds along with their effective targets to make traditional Chinese medicine vital to cover all stages of patients in the treatment and control of COVID-19. CONCLUSION: Traditional Chinese medicine provides new evidence to support the clinical value of TCM for COVID-19.

Transcription factor POU4F2 promotes colorectal cancer cell migration and invasion through hedgehog-mediated epithelial-mesenchymal transition.

As a POU homeodomain transcription factor, POU4F2 has been implicated in regulating tumorigenic processes in various cancers. However, the role of POU4F2 in colorectal cancer (CRC) remains unclear. Here, we revealed that POU4F2 functions as a tumor promotor in CRC. Bioinformatics analysis in specimens from CRC patients and expression analysis in CRC cell lines showed that POU4F2 was upregulated at the mRNA and protein levels in CRC. Depletion of POU4F2 suppressed the metastatic phenotypes of CRC cells, including cell migration, invasion, and the expression of epithelial-mesenchymal transition (EMT) markers. Moreover, depletion of POU4F2 decreased the number of lung metastatic nodes in nude mice. Mechanistically, POU4F2 positively regulated the Hedgehog signaling pathway, as inferred from the downregulation of the expression of sonic Hedgehog homolog, patched 1, Smoothened, and GLI family zinc finger 1 in vitro and vivo following silencing of POU4F2. Furthermore, the SMO agonist SAG reversed the effects of POU4F2 knockdown in CRC. Functionally, POU4F2 contributed to the Hedgehog signaling-regulated activation of the EMT process and promotion of CRC cell migration and invasion. Collectively, these findings elucidated the role of POU4F2 as a tumor promotor in CRC through the regulation of Hedgehog signaling-mediated EMT and suggested that POU4F2 suppression might be a promising therapeutic target in inhibiting CRC metastasis.