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Background: To explore the correlation between left atrial appendage morphology, blood flow velocity and plasma galectin-3 and thrombosis in patients with atrial fibrillation. Methods: Patients with atrial fibrillation who received treatment and completed ultrasound examination in hospital from 2022 to December 2023 were enrolled. According to whether there was left atrial appendage thrombosis, the patients were divided into a control group (no left atrial appendage thrombosis was found) and a study group (left atrial appendage thrombosis was found). The morphology and structure of the left atrial appendage, blood flow velocity and plasma galectin-3 level were recorded exploring its correlation with left atrium thrombosis. Results: A total of 330 patients with atrial fibrillation were enrolled, including 278 in the control group and 52 in the study group. Left group and the control group of morphological structure differences (P < 0.05). The main lobe length, ostial area, longest diameter, shortest diameter, left atrial appendage volume and left atrial volume in the study group were higher than those in the control group (P < 0.05). The left atrial appendage emptying velocity, filling velocity and left ventricular ejection fraction of the study group were lower than those of the control group, and the left ventricular end-diastolic diameter was higher than that of the control group (P < 0.05). Group of white blood cell count, neutrophils/lymphocyte ratio, plasma galactose lectin-3 levels were higher than control group (P < 0.05). ROC curve analysis of left atrial appendage emptying velocity, left atrial appendage filling velocity, left atrial enddiastolic diameter and left atrial ejection fraction had higher diagnostic value (P < 0.05). Conclusions: Left atrial appendage morphology, blood flow velocity and plasma galectin-3 level are important factors to evaluate the risk of left atrial appendage thrombosis in patients with atrial fibrillation. This study improves the understanding of thrombosis, further elucidates the risk factors for thrombosis, and improves patient prognosis.

A six-axis industrial robot kinematics calibration method based on laser scanning measurement arm measurement system is proposed. Firstly，the motion deviation of the robot itself is analyzed and the problem of non-coincidence between the robot coordinate system constructed by the measurement system and the real base calibration system is comprehensively considered. The absolute positioning error equation related to the parameters of each end of the robot is established, based on the error equation，using the portable laser scanning measurement arm measurement system, the flange center point of the robot in different spatial position posture is measured, and the error equation is solved by least square method. By using the calculated parameter error, the nominal parameters in the robot model are corrected, the accuracy of the robot movement can be improved. By applying the method to the Staubli TX90 industrial robot，the experimental results show that the absolute positioning accuracy of the robot is reduced from the mean/standard deviation of 0.742 5 mm/0.191 0 mm before calibration to 0.242 8 mm/0.098 1 mm after calibration，which is increased by nearly 50%，indicating the validity and accuracy of the calibration method.

A cellular automaton model has been developed to simulate the microstructure evolution of a C-Mn steel during the peritectic solidification. In the model, the thermodynamics and solute diffusion of multi-component systems were taken into account by using Thermo-Calc and Dictra software package. Scheil model was used to predict the relationship between the solid fraction and the temperature, which was used to calculate the movement velocity of the L/δ and the L/γ interfaces. A mixed-mode model in multi-component systems was adopted to calculate the movement velocity of the δ/γ interface. To validate the cellular automaton model, the variation of manganese distribution was studied. The simulated results showed a good agreement with experimental results reported in literatures. Meanwhile, the simulated growth kinetics of peritectic solidification agreed well with the experimental results obtained using confocal scanning laser microscopy (CSLM). The model can simulate the growth kinetics of the peritectic solidification and the distribution of concentrations of all components in grains.

Abstract Background Mesenchymal stem cells (MSCs) have been considered to be the attractive vehicles for delivering therapeutic agents toward various tumor diseases. This study was to explore the distribution pattern, kinetic delivery of adenovirus, and therapeutic efficacy of the MSC loading of E1A mutant conditionally replicative adenovirus Adv-Stat3(-) which selectively replicated and expressed high levels of anti-sense Stat3 complementary DNA in breast cancer and melanoma cells. Methods We assessed the release ability of conditionally replicative adenovirus (CRAd) from MSC using crystal violet staining, TCID50 assay, and quantitative PCR. In vitro killing competence of MSCs carrying Adv-Stat3(-) toward breast cancer and melanoma was performed using co-culture system of transwell plates. We examined tumor tropism of MSC by Prussian blue staining and immunofluorescence. In vivo killing competence of MSCs carrying Adv-Stat3(-) toward breast tumor was analyzed by comparison of tumor volumes and survival periods. Results Adv-Stat3(-) amplified in MSCs and were released 4 days after infection. MSCs carrying Adv-Stat3(-) caused viral amplification, depletion of Stat3 and its downstream proteins, and led to significant apoptosis in breast cancer and melanoma cell lines. In vivo experiments confirmed the preferential localization of MSCs in the tumor periphery 24 hours after tail vein injection, and this localization was mainly detected in the tumor parenchyma after 72 hours. Intravenous injection of MSCs carrying Adv-Stat3(-) suppressed the Stat3 pathway, down-regulated Ki67 expression, and recruited CD11b-positive cells in the local tumor, inhibiting tumor growth and increasing the survival of tumor-bearing mice. Conclusions These results indicate that MSCs migrate to the tumor site in a time-dependent manner and could be an effective platform for the targeted delivery of CRAd and the amplification of tumor killing effects.

Abstract Background P21(WAF1/Cip1) binds to cyclin-dependent kinase complexes and inhibits their activities. It was originally described as an inhibitor of cancer cell proliferation. However, many recent studies have shown that p21 promotes tumor progression when accumulated in the cell cytoplasm. So far, little is known about the correlation between cytoplasmic p21 and drug resistance. This study was aimed to investigate the role of p21 in the cisplatin resistance of ovarian cancer. Methods RT-PCR, western blot and immunofluorescence were used to detect p21 expression and location in cisplatin-resistant ovarian cancer cell line C13* and its parental line OV2008. Regulation of cytoplasmic p21 was performed through transfection of p21 siRNA, Akt2 shRNA and Akt2 constitutively active vector in the two cell lines; their effects on cisplatin-induced apoptosis were evaluated by flow cytometry. Tumor tissue sections of clinical samples were analyzed by immunohistochemistry. Results p21 predominantly localizes to the cytoplasm in C13* compared to OV2008. Persistent exposure to low dose cisplatin in OV2008 leads to p21 translocation from nuclear to cytoplasm, while it had not impact on p21 localization in C13*. Knockdown of cytoplasmic p21 by p21 siRNA transfection in C13* notably increased cisplatin-induced apoptosis through activation of caspase 3. Inhibition of p21 translocation into the cytoplasm by transfection of Akt2 shRNA into C13* cells significantly increased cisplatin-induced apoptosis, while induction of p21 translocation into the cytoplasm by transfection of constitutively active Akt2 in OV2008 enhanced the resistance to cisplatin. Immunohistochemical analysis of clinical ovarian tumor tissues demonstrated that cytoplasmic p21 was negatively correlated with the response to cisplatin based treatment. Conclusions Cytoplasmic p21 is a novel biomarker of cisplatin resistance and it may represent a potential therapeutic target for ovarian tumors that are refractory to conventional treatment.

Abstract Background PC cell-derived growth factor (PCDGF), also called epithelin/granulin precursor (GEP), is an 88-kDa secreted glycoprotein with the ability to stimulate cell proliferation in an autocrine fashion. In addition, some studies indicated that PCDGF participated in invasion, metastasis and survival of cancer cells by regulating cell migration, adhesion and proliferation. Yet the effects of PCDGF on proliferation and invasion of ovarian cancer cells in vitro and the mechanisms by which PCDGF mediates biological behaviors of ovarian cancer have rarely been reported. In the present study we investigated whether and how PCDGF/GEP mediated cell proliferation and invasion in ovarian cancer. Methods PCDGF/GEP expression level in three human ovarian cancer cell lines of different invasion potential were detected by RT-PCR and western blot. Effects of inhibition of PCDGF expression on cell proliferation and invasion capability were determined by MTT assay and Boyden chamber assay. Expression levels of cyclin D1 and CDK4 and MMP-2 activity were evaluated in a pilot study. Results PCDGF mRNA and protein were expressed at a high level in SW626 and A2780 and at a low level in SKOV3. PCDGF expression level correlated well with malignant phenotype including proliferation and invasion in ovarian cancer cell lines. In addition, the proliferation rate and invasion index decreased after inhibition of PCDGF expression by antisense PCDGF cDNA transfection in SW626 and A2780. Furthermore expression of CyclinD1 and CDK4 were downregulated and MMP-2 was inactivated after PCDGF inhibition in the pilot study. Conclusion PCDGF played an important role in stimulating proliferation and promoting invasion in ovarian cancer. Inhibition of PCDGF decreased proliferation and invasion capability through downregulation of cyclin D1 and CDK4 and inactivation of MMP-2. PCDGF could serve as a potential therapeutic target in ovarian cancer.

Introduction: While 15 to 20% of cancers are associated with microbial infection, the relationship between oral microorganisms and oral squamous cell carcinoma (OSCC) remains unclear. The location of bacteria in a tumor is closely related to its carcinogenic mechanism. The aim of this study was to analyse bacterial diversity in clinical OSCC tissue samples and tumor distant normal tissues, locate target bacteria, and search for proteins that may interact with target bacteria., Materials and Methods: The 16S rDNA method was used to analyse bacterial diversity in clinical OSCC tissue samples and tumor distant normal tissues. Correlations between Fusobacterium abundance and clinicopathological characteristics were analysed using the χ2 test. The position of target bacteria was analysed by fluorescence in situ hybridization (FISH), and the expression of CK, CD31, CD45, CD68, cyclin D1, β-catenin, E-cadherin, NF-κB, and HIF-1α was analysed by immunohistochemistry (IHC) in OSCC tumor tissues and tumor distant normal tissues., Results: The 16S rDNA results showed that the detected amount of Fusobacterium in OSCC tumor tissues was significantly larger than that in tumor distant normal tissues. High expression of Fusobacterium was significantly correlated with the lifestyle-related oral risk habits, including smoking (p=0.036) and alcohol consumption (p=0.022), but did not correlate with patient sex, age, tumor laterality, tumor size, grade or TNM stage. Fusobacterium nucleatum was enriched in tumor stroma, where CD31+ blood vessels and inflammatory cells (including CD45+ leukocytes and CD68+ macrophages) were densely distributed. Cyclin D1 was mainly expressed in the nucleus of tumor cells. β-catenin was expressed in the tumor cell membrane and was positively expressed in tumor interstitial vascular endothelial cells. E-cadherin was mainly expressed in tumor cell membranes. NF-κB was positively expressed in the cytoplasm of tumor cells, tumor interstitial cells and myo-fibrocytes. HIF-1α was mainly expressed in the cytoplasm of tumor interstitial cells. HIF-1α was highly expressed where Fusobacterium nucleatum was densely distributed., Conclusion: According to our study, the detected amount of Fusobacterium in OSCC tumor tissues was significantly larger than that in tumor distant normal tissues, and Fusobacterium nucleatum might aggravate inflammation and hypoxia by interacting with NF-κB and HIF-1α in OSCC., (©The Author(s) 2023. Open Access. This article is licensed under a Creative Commons CC-BY International License.)