CCL3 and CCL20-recruited dendritic cells modified by melanoma antigen gene-1 induce anti-tumor immunity against gastric cancer ex vivo and in vivo

<p>Abstract</p> <p>Background</p> <p>To investigate whether dendritic cell (DC) precursors, recruited by injection of <b>chemokine ligand 3 (CCL3) and CCL20</b>, induce anti-tumor immunity against gastric cancer induced by a DC vaccine expressing melanoma antigen gene-1 (MAGE-1) ex vivo and in vivo.</p> <p>Methods</p> <p>B6 mice were injected with CCL3 and CCL20 via the tail vein. Freshly isolated F4/80^-B220^-CD11c⁺cells cultured with cytokines were analyzed by phenotype analysis and mixed lymphocyte reaction (MLR). For adenoviral (Ad)-mediated gene transduction, cultured F4/80^-B220^-CD11c⁺cells were incubated with Ad-MAGE-1. Vaccination of stimulated DC induced T lymphocytes. The killing effect of these T cells against gastric carcinoma cells was assayed by MTT. INF-γ production was determined with an INF-γ ELISA kit. In the solid tumor and metastases model, DC-based vaccines were used for immunization after challenge with MFC cells. <b>Tumor size, survival of mice, and number of pulmonary metastatic foci were used to assess the therapeutic effect of DC vaccines</b>.</p> <p>Results</p> <p>F4/80^-B220^-CD11c⁺cell numbers increased after <b>CCL3 and CCL20 </b>injection. Freshly isolated F4/80^-B220^-CD11c⁺cells cultured with cytokines were phenotyically identical to typical DC and gained the capacity to stimulate allogeneic T cells. These DCs were transduced with Ad-MAGE-1, which were prepared for DC vaccines expressing tumor antigen. T lymphocytes stimulated by DCs transduced with Ad-MAGE-1 exhibited specific killing effects on gastric carcinoma cells and produced high levels of INF-γ ex vivo. In vivo, tumor sizes of the experimental group were much smaller than both the positive control group and the negative control groups (<it>P </it>< 0.05). Kaplan-Meier survival curves showed that survival of the experimental group mice was significantly longer than the control groups (<it>P </it>< 0.05). In addition, MAGE-1-transduced DCs were also a therapeutic benefit on an established metastatic tumor, resulting in a tremendous decrease in the number of pulmonary metastatic foci.</p> <p>Conclusions</p> <p><b>CCL3 and CCL20</b>-recruited DCs modified by adenovirus-trasnsduced, tumor-associated antigen, MAGE-1, can stimulate anti-tumor immunity specific to gastric cancer ex vivo and in vivo. This system may prove to be an efficient strategy for anti-tumor immunotherapy.</p

Effectiveness of early rhythm control in improving clinical outcomes in patients with atrial fibrillation:a systematic review and meta-analysis

BackgroundCurrent guidelines recommend rhythm control for improving symptoms and quality of life in symptomatic patients with atrial fibrillation (AF). However, the long-term prognostic outcomes of rhythm control compared with rate control are still inconclusive. In this meta-analysis, we aimed to assess the effects of early rhythm control compared with rate control on clinical outcomes in newly diagnosed AF patients.MethodsWe systematically searched the PubMed and Embase databases up to August 2022 for randomized and observational studies reporting the associations of early rhythm control (defined as within 12 months of AF diagnosis) with effectiveness outcomes. The primary outcome was a composite of death, stroke, admission to hospital for heart failure (HF), or acute coronary syndrome (ACS). Hazard ratios (HRs) and 95% confidence intervals (CIs) from each study were pooled using a random-effects model, complemented with an inverse variance heterogeneity or quality effects model.ResultsA total of 8 studies involving 447,202 AF patients were included, and 23.5% of participants underwent an early rhythm-control therapy. In the pooled analysis using the random-effects model, compared with rate control, the early rhythm-control strategy was significantly associated with reductions in the primary composite outcome (HR = 0.88, 95% CI: 0.86-0.89) and secondary outcomes, including stroke or systemic embolism (HR = 0.78, 95% CI: 0.71-0.85), ischemic stroke (HR = 0.81, 95% CI: 0.69-0.94), cardiovascular death (HR = 0.83, 95% CI: 0.70-0.99), HF hospitalization (HR = 0.90, 95% CI: 0.88-0.92), and ACS (HR = 0.86, 95% CI: 0.76-0.98). Reanalyses using the inverse variance heterogeneity or quality effects model yielded similar results.ConclusionsOur current meta-analysis suggested that early initiation of rhythm control treatment was associated with improved adverse effectiveness outcomes in patients who had been diagnosed with AF within 1 year.RegistrationThe study protocol was registered to PROSPERO (CRD42021295405)

Clinicopathologic Significance of HIF-1α, CXCR4, and VEGF Expression in Colon Cancer

We investigated the clinicopathologic significance of HIF-1, CXCR4, and VEGF expression using immumohistochemistry in human colon cancer. HIF-1, CXCR4, and VEGF high expression levels were correlated positively with TNM stage, lymph node involvement, and distant metastasis Furthermore, we found that combined high expression of any two of the three molecules (P = .028 for HIF-1/CXCR4, P = .007 for HIF-1/VEGF, and P = .004 for CXCR4/VEGF) had stronger correlation with lymph node metastasis than did each alone. However, a relationship with distant metastasis is seen only with the combinations CXCR4/VEGF (P = .069 for HIF-1/CXCR4, P = .062 for HIF-1/VEGF, and P = .035 for CXCR4/VEGF) as compared with those of single molecule high expression alone. Combined expression of all three molecules strongly correlates with lymph node metastasis and distant metastasis. The mRNA expression of HIF-1, CXCR4, and VEGF were quantified by real-time PCR in different colon cancer tissue samples, the experiment results shown that fresh colon tissue samples significantly overexpressed CXCR4 and VEGF mRNA compared with negative control. Therefore, the disease-free survival of all patients after curative resection can be considered in association with all three markers expression

Feasibility of laparoscopic enucleation for hemangioma in special hepatic segments

Background and aimThis study aims to evaluate the safety and efficacy of laparoscopic enucleation for liver hemangioma in special hepatic segments.MethodsWe retrospectively reviewed 58 patients who underwent laparoscopic surgery for hepatic hemangioma at a single center from January 2016 to January 2022. Segments I, IVa, VII, and VIII are defined as special hepatic segments, attributing to the bad visualization and adjacent to important vessels such as hepatic veins and inferior vena cava that lead to a high risk in laparoscopic surgery. Patients were categorized into a special location group (SLG) and a normal location group (NLG) according to the location of hemangioma. General data, intraoperative and postoperative outcomes, and postoperative complications of the two groups were compared and analyzed.ResultsThere were no significant differences in age (p = 0.288), gender (p = 0.331), body mass index (p = 0.168), the maximum diameter of hemangioma (p = 0.330), ASA risk grading (p = 0.615), and comorbidities (p &gt; 0.05) between the two groups. The operation time (p &lt; 0.001), intraoperative blood loss (p &lt; 0.001), and intraoperative blood transfusion rate (p = 0.047) were significantly higher in the SLG. The rate of conversion to laparotomy was higher in the SLG, but there was no significant difference (p = 0.089). In addition, the exhaust time (p = 0.03) and postoperative hospital stay (p &lt; 0.01) were significantly shorter in the NLG. The postoperative complications were comparable between the two groups, and there were no perioperative deaths.ConclusionLaparoscopic enucleation of hemangioma in special hepatic segments is difficult and has a critical risk of massive bleeding during surgery. Meanwhile, it is also safe, feasible, and effective

Study and Design of Diaphragm Pump Vibration Detection Fault Diagnosis System Based on FFT

Abstract: This study has proposed a fault diagnosis system based on vibration detection. The system mainly includes four modules: signal acquisition module, signal processing module, state identification module, fault diagnosis and alarm module. The system uses CMSS 2200 acceleration sensor to collect vibration signals, processing spectrum with FFT (Fast Fourier Transform) which is used effectively in current industry and finally achieve fault diagnosis and prediction for diaphragm pump. Through collection and analysis of the history signal data, set threshold value in the fault diagnosis system. According to the characteristics of different types, set the corresponding effective threshold value. The simulation results show that, the spectrum after FFT transformation processing, can really and effectively reflect equipment operating condition of the diaphragm. This system is not only simple and stable, but also can predict pump failure effectively, so that it reduces equipment downtime, plan maintenance time and unplanned maintenance time

Alteration of CXCR7 Expression Mediated by TLR4 Promotes Tumor Cell Proliferation and Migration in Human Colorectal Carcinoma

The link between inflammation and colorectal carcinoma has been acknowledged. However, the impact of bacterial lipopolysaccharide (LPS) binding to Toll-like receptor 4 (TLR4) on chemokine receptors in human colorectal carcinoma cells still remains to be elucidated. The present study shows that exposure to LPS elevated CXC chemokine receptor 7 (CXCR7) expression in colorectal carcinoma SW480 and Colo 205 cell lines expressing TLR4/myeloid differential protein (MD-2). CXCR7 is associated with SW480 cell proliferation and migration. However, exposure of SW480 and Colo 205 cells to LPS had no effect on CXCR4 expression. To further support the above results, the expression of TLR4, MD-2, and CXCR7 was analyzed in human colorectal carcinoma tissues. Higher rates of TLR4 (53%), MD-2 (70%), and CXCR7 (29%) expression were found in colorectal carcinoma tissues than in normal tissues. We demonstrated that the recombination of TLR4, MD-2 and CXCR7 strongly correlated with tumor size, lymph node metastasis and distant metastasis in colorectal carcinoma tissue samples (p = 0.037, p = 0.002, p = 0.042, resp.). Accordingly, simultaneous examination of the expression of TLR4, MD-2 and CXCR7 in cancer tissues of colorectal carcinoma may provide valuable prognostic diagnosis of carcinoma growth and metastasis. Interplay of TLR4, MD-2 and CXCR7 may be of interest in the context of novel immunomodulatory therapies for colorectal carcinoma