Abstract Background Circulating tumour cells (CTCs), especially mesenchymal CTCs, are important determinants of metastasis, which leads to most recurrence and mortality in hepatocellular carcinoma (HCC). However, little is known about the underlying mechanisms of CTC colonisation in pre-metastatic niches. Methods Detection and classification of CTCs in patients were performed using the CanPatrol™ system. A lentiviral vector expressing Prrx1-targeting shRNA was constructed to generate a stable HCC cell line with low expression of Prrx1. The effect of Prrx1 knockdown on stemness, migration, and drug resistance of the cell line was assessed, including involvement of SDF-1/CXCR4 signalling. Promising clinical applications of an inhibitor of STAT3 tyrosine phosphorylation, C188–9, and specific blockade with CXCR4 antibody were explored. Results The number of mesenchymal CTCs in blood was closely associated with tumour recurrence or metastasis. Pre-metastatic niche-derived SDF-1 could downregulate Prrx1, which induced the stemness, drug resistance, and increased expression of CXCR4 in HCC cells through the STAT3 pathway in vitro. In vivo , mice bearing tumours of Prrx1 low-expressing cells had significantly shorter survival. In xenograft tumours and clinical samples, loss of Prrx1 was negatively correlated with increased expression of CXCR4 in lung metastatic sites compared with that in the primary foci. Conclusions These findings demonstrate that decreased expression of Prrx1 stimulates SDF-1/CXCR4 signalling and contributes to organ colonisation with blood CTCs in HCC. STAT3 inhibition and specific blockade of CXCR4 have clinical potential as therapeutics for eliminating organ metastasis in advanced HCC.
To measure the multidrug resistance gene (MDR1) messenger RNA (mRNA) content of ovarian carcinoma and to investigate the clinical significance of MDR1 expression in ovarian carcinoma.A sensitive assay based on the polymerase chain reaction (PCR) was used to measure MDR1 mRNA in biopsy samples of 35 ovarian carcinoma, 20 ovarian benign tumors and 17 normal controls. Pathological diagnosis was made from these samples.(1) The expression rate of MDR1 in ovarian carcinomas was 57.1%, but there was no expression in benign ovarian tumors and in the normal controls. (2) 40.9% of patients given primary treatments and 84.6% of patients previously treated but with relapses had over expression of MDR1 gene. (3) The positive expression rate of MDR1 in cancer lesion, its adjacent sites and metastasis was 52.9%, 11.8% and 70.6% respectively. (4) The response rate to chemotherapy was lower in patients with overexpression of MDR1 gene than in patients without such expression. (5) No significant correlation was observed when the positive rate of expression of MDR1 in cancer tissues was analyzed against clinical stages and pathological types.The overexpression of MDR1 was correlated with acquired drug-resistance in patients with ovarian caracinoma. Measurement of the expression of MDR1 in a patient's tumor may be of value clinically in detecting drug-sensitivity and in predicting prognosis.
Purpose: Obtaining a better understanding of the pathogenesis of primary angle-closure disease (PACD) still requires studies that provide measurements of anterior and posterior biometric characteristics together and that assess the relationship between them. Methods: In total, 201 eyes were enrolled in this cross-sectional study: 50 normal controls, 49 primary angle-closure suspect (PACS), 38 primary angle closure (PAC), and 64 primary angle-closure glaucoma (PACG) eyes. The anterior and posterior structural features were measured by anterior segment optical coherence tomography and swept-source optical coherence tomography. Results: All PACD groups had smaller anterior chamber depth (ACD), anterior chamber area (ACA), anterior chamber volume (ACV), angle opening distance at 750 μm from the scleral spur (AOD750), trabecular–iris space area at 750 μm from the scleral spur (TISA750), and angle recess area (ARA), as well as a larger lens vault (LV), than controls (all P < 0.001). The PACS and PAC groups had thicker iris thickness at 750 μm from the scleral spur (IT750) than controls ( P = 0.017 and P = 0.002, respectively). Choroidal thickness (CT) was not statistically different among normal, PACS, PAC, and PACG eyes. Univariate and multivariate linear regression analysis revealed a significant association between thinner IT750 and increased CT in PACD eyes ( P = 0.031, univariate analysis; P = 0.008, multivariate analysis). Conclusion: Thinner iris thickness was associated with increased CT in PACD eyes; however, the underlying mechanism needs further investigation.
To verify the clinical value of the good outcome following attempted resuscitation (GO-FAR) score in predicting the neurological status of patients with in-hospital cardiac arrest (IHCA) in the Chinese population.The clinical data of patients with IHCA who were admitted to the Zigong Fourth People's Hospital from January 1 to December 31, 2020 were retrospectively analyzed. Used Glasgow-Pittsburgh cerebral performance category (CPC) score 1 point as the end point, the subjects were divided into 4 groups according to the score: ≤ 0 group, 1-8 group, 9-20 group and ≥ 21 group. Taken the group which GO-FAR score ≤ 0 as the reference group, the odds ratio (OR) of the other three groups compared with this group was calculated. The receiver operator characteristic curve (ROC curve) was performed to evaluate the predictive value of the GO-FAR score in favorable neurological outcome. A calibration curve was drawn for the Hosmer-Lemeshow test to analyze the degree of calibration of the GO-FAR score for predicting good neurological outcome.A total of 230 IHCA patients were enrolled in the study, including 130 males, aged 74 (65, 81) years old, and 23 case (10.0%) had good neurological prognosis. There were statistically significant differences in GO-FAR-related variables, including age, a normal neurological function on admitted, acute stroke, metastatic cancer, septicemia, medical noncardiac admission, hepatic insufficiency, hypotension, renal insufficiency or dialysis, respiratory insufficiency, pneumonia, etc (all P < 0.05). Taken the GO-FAR score ≤ 0 group as the reference group, the OR values of good neurological prognosis in the GO-FAR score 1-8 group were 0.54 [95% confidence interval (95%CI) was 0.17-1.53, P = 0.250], 9-20 group were 0.17 (95%CI was 0.02-0.67, P = 0.009) and ≥ 21 group were 0.25 (95%CI was 0.05-0.85, P = 0.025). The area under the ROC curve (AUC) of the GO-FAR score for predicting favorable neurological outcome in IHCA patients was 0.653 (95%CI was 0.529-0.777, P = 0.015) and there was no significant difference in Hosmer-Lemeshow test (P = 0.311). All these suggested that there was no significant difference between the predicted value and the actual value.GO-FAR score can be applied to predict neurological prognosis of IHCA patients in Chinese population. It can help clinicians to predict the prognosis of cardio-pulmonary resuscitation (CPR) and propose critical recommendations in treatment for these patients or their families.
To clarify the effects of TNFSF4 (rs3850641) polymorphisms on coronary heart disease (CHD) risk.Published literature from Pubmed, Embase, ISI Wed of Knowledge, Cochrane Library, and Chinese databases were retrieved. All studies evaluating the association between TNFSF4 (rs3850641) polymorphisms and CHD risk were included. Summary odds ratios (ORs) and 95% confidence intervals (CI) were calculated employing random-effects models irrespective of between-study heterogeneity.A total of 9 eligible studies was included in this meta-analysis. Overall analysis showed that the rs3850641 G allele was not associated with CHD, compared with the A allele, with OR of 1.10 (95% CI, 0.96-1.27; p = 0.174). Genotypic analysis showed that there was no significant association between the GG, GA, GG + GA, and CHD, compared with participants with AA, with ORs of 1.23 (95% CI, 0.75-2.03; p = 0.409), 1.04 (95% CI, 0.84-1.29; p = 0.705), and 1.07 (95% CI, 0.85-1.34; p = 0.589), respectively. On the other hand, in the subgroup analysis by ethnicity, source of controls, genotyping methods, or matching criteria, there was still no statistically significant association between TNFSF4 (rs3850641) polymorphisms and CHD risk.This meta-analysis reveals that TNFSF4 (rs3850641) polymorphisms is not associated with CHD risk.
Hepatocellular carcinoma (HCC) is an aggressive form of cancer characterized by a high recurrence rate following resection. Studies have implicated stromal and immune cells, which form part of the tumor microenvironment, as significant contributors to the poor prognoses of HCC patients. In the present study, we first downloaded gene expression datasets for HCC patients from The Cancer Genome Atlas database and categorized the patients into low and high stromal or immune score groups. By comparing those groups, we identified differentially expressed genes significantly associated with HCC prognosis. The Gene Ontology database was then used to perform functional enrichment analysis, and the STRING network database was used to construct protein-protein interaction networks. Our results show that most of the differentially expressed genes were involved in immune processes and responses and the plasma membrane. Those results were then validated using another a dataset from a HCC cohort in the Gene Expression Omnibus database and in 10 pairs of HCC tumor tissue and adjacent nontumor tissue. These findings enabled us to identify several tumor microenvironment-related genes that associate with HCC prognosis, and some those appear to have the potential to serve as HCC biomarkers.
This meta-analysis aims to clarify the effects of depression on the risk of ventricular arrhythmias.A systematic search was performed in PubMed, EMBASE, Web of Science, and the Cochrane Library. Summary hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated employing random-effects models. Publication bias of the literature was evaluated using Begg's funnel plots and Egger's test.A total of nine prospective cohort studies were included in this meta-analysis. Overall, participants with depression, as compared to those who had no depression, experienced a significantly increased risk of developing ventricular arrhythmia (combined HR, 1.33; 95% CI, 1.02 - 1.73; p = 0.037). In a subgroup analysis, a statistically-significant relation between depression and risk of ventricular arrhythmia was observed in coronary heart disease (CHD) patients and in studies with adjustment for confounding factors, with pooled HR at a 95% CI of 1.78 (1.31 - 2.42) and 1.52 (1.11 - 2.08), respectively. No publication bias was detected by Begg's funnel plot and Egger's test.This meta-analysis suggests that depression in patients was associated with increased risk of developing ventricular arrhythmias, especially in patients with CHD. Cardiologists and psychiatrists should be alert to the risk of ventricular arrhythmia in patients with depression. Moreover, the antidepressant medications (e.g., tricyclic antidepressants and selective serotonin reuptake inhibitors) that could affect heart rate variability should be used carefully.
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