Search

Human hemodynamic responses during exposure to multi-axial acceleration was a relatively new topic in the fields of acceleration physiology. This study aimed to focus on these responses, especially variations of blood perfusion to brain and eyes, through mathematical modeling. A mathematical model was established using lumped parameter methods, containing compartments of four heart chambers, systemic arteries and veins, circulation of typical systemic organs, and some compartments for pulmonary circulation, together with autonomic regulation considered. This model was firstly validated by using experimental data from experiment of posture change and centrifuge tests of +Gz accelerations, and then applied to analyze human hemodynamic responses to typical multi-axial accelerations. Validation results demonstrated the mathematical model could generate reasonable responses of human cardiovascular system during posture change and exposure to +Gz accelerations. Simulation results of hemodynamic responses to multi-axial accelerations depicted Gy induced significant differences of blood flow to the left and right eyes. And some contour maps were generated based on these results, which provided a quick way to estimate blood flow variations in brain and eyes during exposure to different accelerations. Graphical Abstract This study aimed to focus on variations of blood perfusion to brain and eyes during exposure to typical multi-axial accelerations through mathematical modeling. This model was firstly validated by using experimental data from experiment of posture change and centrifuge tests of +Gz accelerations, and then applied to analyze human hemodynamic responses to typical multi-axial accelerations. Simulation results of hemodynamic responses to multi-axial accelerations depicted Gy induced significant differences of blood flow to the left and right eyes. And contour maps that generated based on these results provided a quick way to estimate blood flow variations in brain and eyes during exposure to different accelerations., (© 2021. International Federation for Medical and Biological Engineering.)

Background: Variations in the anatomy of the hepatic artery are common. This study was aimed at sharing our experience with identifying and protecting the aberrant hepatic artery (AHA) and discussing its impact on the resection margin and outcomes of laparoscopic pancreatoduodenectomy (LPD)., Methods: A total of 576 patients who underwent LPD between 2015 and 2020 were retrospectively selected and divided into AHA and no AHA groups for this study. The demographics of the patients, pathological features, surgical data, and postoperative complications were further compared and analyzed between the two groups., Results: The AHA group included 127 patients (22.05%). No statistically significant differences were found between the AHA and no AHA groups in the intraoperative data, postoperative complications, and long-term survival with malignant tumor. There was also no significant difference in the R1 rate for pancreatic adenocarcinoma., Conclusions: AHA appears frequently; however, it does not change the incidence of perioperative adverse events following LPD or the long-term prognosis of malignant tumor. The preservation of AHA during surgery can be achieved with a well-planned approach and careful dissection., (© 2021. Société Internationale de Chirurgie.)

The design and construction of synthetic therapeutic protocells capable of establishing cognate chemical communication channels with living cells is an important challenge for synthetic biology and bio-engineering. Here we develop a step towards protocell-mediated nitric-oxide-induced vasodilation by constructing a new synthetic cell model based on bio-derived coacervate vesicles with high haemocompatibility and increased blood circulation times. The hybrid protocells are prepared by the spontaneous self-assembly of haemoglobin-containing erythrocyte membrane fragments on the surface of preformed polysaccharide-polynucleotide coacervate micro-droplets containing glucose oxidase. We use the sequestered enzymes to program a spatially coupled glucose oxidase/haemoglobin reaction cascade, which in the presence of glucose and hydroxyurea generates a protocell-mediated flux of nitric oxide that we exploit for in vitro and in vivo blood vessel vasodilation. Taken together, our results provide new opportunities for the development of endogenously organized cell-like entities (biocompatible micro-bots) geared specifically towards active interfacing with individual living cells and cell communities.

Hepatic artery variations increase the difficulty of laparoscopic pancreaticoduodenectomy (LPD). The safety and efficacy of LPD in the presence of aberrant hepatic arteries (AHA) must be further verified.Patients with normal and variant hepatic arteries who underwent LPD and preoperative arterial angiography were retrospectively analyzed. Variation type, intraoperative management, and clinical treatment outcomes were compared.There were 54 cases (24.8%) of AHA. The most common hepatic artery variation was accessory right hepatic artery (RHA) from the superior mesenteric artery (SMA, n = 12, 5.5%), followed by replaced RHA from the SMA (n = 10, 4.6%), accessory left hepatic artery from the SMA (n = 10, 4.6%), and replaced common hepatic artery from the SMA (n = 6, 2.8%). Each type of arterial variation was successfully preserved in all cases, and there were no significant effects on the evaluated surgical indices, conversion rate, incidence of postoperative complications, or follow-up results.Our findings indicated that preservation of AHAs during total LPD is feasible. There were no significant effects on surgical indices, incidence of postoperative complications, or follow-up outcomes.The influence of AHA on the safety and efficacy of LPD must be further verified. Patients with normal and variant hepatic arteries who underwent LPD and preoperative arterial angiography were retrospectively analyzed. There were 54 cases (24.8%) of AHA. There were no significant effects of AHAs on surgical indices, incidence of postoperative complications, or follow-up outcomes.

CD160 is an Ig-like glycoprotein expressed by the majority of circulating natural killer cells and γδ T cells. Whether CD160 could regulate CD8 + T-cell functions remains unknown. In this study, we investigated the effects of CD160 on CD8 + T cells in pancreatic cancer. First, we found that the frequency of PD-1 + cells was comparable between CD160 + and CD160 - CD8 + T cells, with the former presenting significantly higher PD-1 expression level. In contrast, the frequency of TIM-3 + cells was higher among CD160 + cells but the expression level was comparable between CD160 + and CD160 - CD8 + T cells. The IFN-γ and IL-2-expressing CD8 + T cells, directly ex vivo, were highly enriched in the CD160 + subset. However, when CD160 + and CD160 - CD8 + T cells were stimulated, the proliferation levels of CD160 + and CD160 - cells were initially comparable, but were significantly lower in CD160 + CD8 + T cells than in CD160 - CD8 + T cells later on. The IFN-γ and IL-2 transcription levels were initially higher in CD160 + CD8 + T cells, but eventually reduced in CD160 + CD8 + T cells compared to CD160 - CD8 + T cells. Also, CD160 + CD8 + T cells presented lower cytotoxic capacity than CD160 - CD8 + T cells. Interestingly, we observed that tumor-infiltrating CD8 + T cells were significantly enriched with the CD160 + subset in pancreatic cancer patients. In addition, patients with higher frequencies of tumor CD160 + CD8 + T cells presented lower survival. Overall, these data demonstrated that tumor-infiltrating CD8 + T cells were enriched with the CD160 + subset in pancreatic cancer, with active effector responses directly ex vivo but limited potential for further activation.

Background: The Cadherin-11 and PI3K/Akt pathway are increasingly recognized as the potential therapeutic target of osteoarthritis (OA) synovitis. The study aimed to investigate the role of PI3K/Akt signaling pathway in the expression of Cadherin-11 and migration and invasive capacity of fibroblast-like synoviocytes (FLS) of OA patients under stimulation of TNF-α and to explore the effect of the PI3K/Akt inhibitor and Cadherin-11 antibody in the therapy of the collagenase-induced osteoarthritis (CIOA) mice., Methods: FLS were primarily cultured from synovium of osteoarthritic patients during total knee arthroplasty. Under the simulation of TNF-α, with or without PI3K/Akt inhibitor LY294002, Cadherin-11 expression was detected by real-time PCR and Western blot, as well as the migration and invasive capacity changes of OA FLS. Cadherin-11 antibody was injected intraarticularly or LY294002 was injected intraperitoneally in CIOA mice to evaluate the changes of synovitis score, cartilage damage, and Cadherin-11 expression., Results: TNF-α stimulation increased Cadherin-11 expression at mRNA and protein level in OA FLS and also increased the phosphorylation-dependent activation of Akt. PI3K inhibitor LY294002 attenuated TNF-α-induced overexpression of Cadherin-11 and decreased the invasive capacity of OA FLS. Intraperitoneal injection of PI3K inhibitor LY294002 could decrease the Cadherin-11 protein expression in synovium of CIOA mice, although it has no significant inhibitory effect on synovitis and cartilage damage. Intraarticular injection of Cadherin-11 antibody attenuated the synovitis and cartilage damage in the CIOA joints and decreased Cadherin-11 expression in the synovial lining., Conclusions: PI3K/Akt pathway was associated with TNF-α-induced activation of OA FLS, which may involve in the pathogenesis of osteoarthritis. Anti-Cadherin-11 therapy in CIOA mice could attenuate the pathological changes of OA joints.

Background: Emerging evidence indicates that Long non-coding RNAs (LncRNAs) and microRNAs (miRNAs) play crucial roles in tumor progression, including hepatocellular carcinoma (HCC). However, whether there is a crosstalk between LncRNA pituitary tumor-transforming 3 (PTTG3P) and miR-383 in HCC remains unknown. This study is designed to explore the underlying mechanism by which LncRNA PTTG3P sponges miR-383 during HCC progression., Methods: qPCR and Western blot were used to analyze LncRNA PTTG3P, miR-383 and other target genes' expression. CCK-8 assay was performed to examine cell proliferation. Annexin V-PE/PI and PI staining were used to analyze cell apoptosis and cell cycle distribution by flow cytometry, respectively. Transwell migration and invasion assays were used to examine cell migration and invasion abilities. An in vivo xenograft study was performed to detect tumor growth. Luciferase reporter assay and RNA pull-down assay were carried out to detect the interaction between miR-383 and LncRNA PTTG3P. RIP was carried out to detect whether PTTG3P and miR-383 were enriched in Ago2-immunoprecipitated complex., Results: In this study, we found that PTTG3P was up-regulated in HCC tissues and cells. Functional experiments demonstrated that knockdown of PTTG3P inhibited cell proliferation, migration and invasion, and promoted cell apoptosis, acting as an oncogene. Mechanistically, PTTG3P upregulated the expression of miR-383 targets Cyclin D1 (CCND1) and poly ADP-ribose polymerase 2 (PARP2) by sponging miR-383, acting as a competing endogenous RNA (ceRNA). The PTTG3P-miR-383-CCND1/PARP2 axis modulated HCC phenotypes. Moreover, PTTG3P also affected the PI3K/Akt signaling pathway., Conclusion: The data indicate a novel PTTG3P-miR-383-CCND1/PARP2 axis in HCC tumorigenesis, suggesting that PTTG3P may be used as a potential therapeutic target in HCC.

In order to improve the accuracy and efficiency of automatic seizure detection, the paper proposes a method based on improved genetic algorithm optimization back propagation (IGA-BP) neural network for epilepsy diagnosis, and uses the method to achieve detection of clinical epilepsy rapidly and effectively. Firstly, the method extracted the linear and nonlinear features of the epileptic electroencephalogram (EEG) signals and used a Gaussian mixture model (GMM) to perform cluster analysis on EEG features. Next, expectation maximization (EM) algorithm was used to estimate GMM parameters to calculate the optimal parameters for the selection operator of genetic algorithm (GA). The initial weights and thresholds of the BP neural network were obtained through using the improved genetic algorithm. Finally, the optimized BP neural network is used for the classification of the epileptic EEG signals to detect the epileptic seizure automatically. Compared with the traditional genetic algorithm optimization back propagation (GA-BP), the IGA-BP neural network can improve the population convergence rate and reduce the classification error. In the process of automatic detection of epilepsy, the method improves the detection accuracy in the automatic detection of epilepsy disorders and reduced inspection time. It has important application value in the clinical diagnosis and treatment of epilepsy.

An unequal loss of peripheral vision may happen with high sustaining multi-axis acceleration, leading to a great potential flight safety hazard. In the present research, finite element method was used to study the mechanism of unequal loss of peripheral vision. Firstly, a 3D geometric model of skull was developed based on the adult computer tomography (CT) images. The model of double eyes was created by mirroring with the previous right eye model. Then, the double-eye model was matched to the skull model, and fat was filled between eyeballs and skull. Acceleration loads of head-to-foot (G z ), right-to-left (G y ), chest-to-back (G x ) and multi-axis directions were applied to the current model to simulate dynamic response of retina by explicit dynamics solution. The results showed that the relative strain of double eyes was 25.7% under multi-axis acceleration load. Moreover, the strain distributions showed a significant difference among acceleration loaded in different directions. It indicated that a finite element model of double eyes was an effective means to study the mechanism of an unequal loss of peripheral vision at sustaining high multi-axis acceleration.

MicroRNAs (miRNAs) are a class of small, non-coding RNAs that play a crucial role in tumor procession. It has been demonstrated that miR-449a expression was downregulated and served as tumor suppressor in many types of tumor. However, the biological function and molecular mechanism of miR-449a in hepatocellular carcinoma (HCC) still remains largely unknown. Therefore, the aims of this study were to investigate biological role and molecular mechanism of miR-449a in HCC by a serial of molecular experiments. Here, we demonstrated that miR-449a expression was downregulated in HCC tissues and cell lines compared with the adjacent nontumor tissues and normal hepatic cell line. Ectopic expression of miR-449a suppressed HCC cell proliferation, colony formation, migration and invasion. Moreover, A Disintegrin And Metalloproteinases 10 (ADAM10) was identified as a direct target gene of miR-449a in HCC cell. ADAM10 expression was upregulated in HCC tissues and cell lines, and was negatively correlated with the expression level of miR-449a in HCC tissues. Interesting, overexpression of ADAM10 attenuated the inhibition effect of miR-449a-mediated HCC cell proliferation, colony formation, migration and invasion. These results suggested that miR-449a might function as a tumor suppressor miRNA, at least in part, through regulating ADAM10 expression in HCC.

Accumulating evidence suggests that miR-138 expression was frequently downregulated in different cancer types and involves in the progression of tumorigenesis. However, the biological role and molecular mechanism of miR-138 involvement in hepatocellular carcinoma (HCC) still remains largely unknown. Therefore, in the present study, we investigated the role of miR-138 in the progression of HCC. We found that miR-138 expression levels were significantly downregulated in HCC tissues and cell lines compared with the corresponding noncancerous liver tissues and normal hepatic cell line. In addition, we also found that enforced expression of miR-138 inhibited proliferation, colony formation, migration and invasion in HCC cells. Using a luciferase reporter assay, SOX9 was confirmed as a direct target of miR-138. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assay showed that overexpression of miR-138 in HCC cells significantly inhibited SOX9 expression on mRNA level and protein level. Furthermore, SOX9 expression was significantly upregulated in HCC tissues and cell lines, and its mRNA expression is negative correlated with miR-138 expression in clinical HCC tissues (r=-0.689, P<0.01). Of note, downregulation of SOX9 performed similar effects with overexpression of miR-138. These findings suggested that miR-138 functioned as a tumor suppressor in HCC partially via repressing SOX9 expression.

Objective: To observe the changes of synovial inflammation score and expression of related molecular markers in patients with rheumatoid arthritis treated with tumor necrosis factor (TNF) antagonist etanercept., Methods: Sixteen patients with rheumatoid arthritis received synovectomy in the knee under arthroscopy, of which 8 patients had been treated with etanercept before surgery (etanercept group) and the other 8 patients were given no etanercept or other biologics (non-biological agent group). The synovial tissues obtained from surgery were subjected to HE staining and immunohistochemical staining respectively, to assess Rooney's inflammation score and detect the expressions of proliferating cell nuclear antigen (PCNA), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and cadherin-11., Results: Rooney's score in etanercept group was significantly lower than that in non-biological agent group. The expressions of PCNA and cadherin-11 in synovial lining and sublining layers significantly decreased in etanercept group. Expressions of VCAM-1 and ICAM-1 had no significant difference in either synovial lining or sublining layer between the two groups. Clinical inflammatory markers including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), platelet count (PLT) and disease activity score in 28 joints (DAS28) had no statistical correlation with Rooney's inflammation score., Conclusion: Etanercept could effectively inhibit proliferation of synoviocytes and infiltration of lymphocytes in synovium of rheumatoid arthritis, and decrease the expressions of proliferation-and adhesion-related molecular markers, which histologically alleviated the synovial inflammation of rheumatoid arthritis. Clinical inflammatory markers might not fully reflect histological changes in the local synovial tissue.

A disintegrin and metalloprotease 10 (ADAM10) is a transmembrane protein associated with metastasis in a number of types of cancer. Little is known, however, regarding the role of ADAM10 in hepatocellular carcinoma (HCC). The aim of the present study was to evaluate whether downregulation of ADAM10 effects HCC cell proliferation, cell cycle, cell migration and cell invasion. A recombinant small hairpin RNA expression vector carrying ADAM10 was constructed and then transfected into the HepG2 human HCC cell line. In vitro cell proliferation, cell cycle, cell migration and cell invasion, and in vivo tumor growth were determined following the downregulation of ADAM10 by RNA interference. The results revealed that downregulation of ADAM10 expression in HepG2 tumor cells using the RNA silencing approach significantly suppressed cell proliferation, cell migration and cell invasion in vitro, and tumor growth in vivo. Furthermore, ADAM10 silencing was able to significantly reduce constitutive phosphorylation of phosphoinositide 3-kinase (PI3K) and Akt, which implies that ADAM10 is, at least partially, involved in the activation of the PI3K/Akt signaling pathway. These results suggest that ADAM10 is important in regulating the proliferation and metastasis of HCC. Thus, ADAM10 is a promising therapeutic target for the prevention of tumor metastases in HCC.

Objective: To explore the pattern of cadherin-11 expression and its relationship with synovial inflammation in rheumatoid arthritis (RA), and study the regulatory effects of cytokines on cadherin-11 expression on RA fibroblast-like synoviocytes (RAFLS)., Methods: Synovium samples were obtained from 28 RA patients who were undergoing total knee replacement. After HE staining, synovitis score was determined according to Rooney's inflammation score system. The expression of cadherin-11 in RA synovium was semi-quantified by immunohistochemical staining, and its correlations with Rooney's inflammation score and systematic inflammatory markers were analyzed statistically. After induction with transforming growth factor β (TGF-β) or interleukin 17 (IL-17) at a series of concentrations, the expression of cadherin-11 on RAFLS was assessed by real time guantitative-PCR and Western blotting., Results: There was no significant difference in cadherin-11 expression in RA synovium among different levels of C-reactive protein. Cadherin-11 in the lining and sublining layers were positively correlated with D-dimer, synovial lining layer hyperplasia, proliferating blood vessels, perivascular infiltration of lymphocytes, focal aggregation of lymphocytes and diffuse infiltration of lymphocytes; cadherin-11 in the lining layer was negatively correlated with interstitial fibrosis. TGF-β or IL-17 stimulation could up-regulate cadherin-11 expression on RAFLS at mRNA and protein levels., Conclusion: The over-expression of cadherin-11 in RA was correlated with synovial lining layer hyperplasia, proliferating blood vessels and infiltration of lymphocytes. Cadherin-11 expression on RAFLS could be induced by TGF-β and IL-17 induction.

Pain in the cervical region of air force pilots, who are exposed to high G-forces, is a specifically occupational health problem. To minimize neck problems, the cervical muscles need specific strength exercise. It is important that the training for the neck must be carried out with optimal resistance in exercises. The model NSE-1 neck training machine for pilots was designed for neck strengthening exercises under safe and effective conditions. In order to realize the functions of changeable velocity and resistant (CVR) training and neck isometric contractive exercises, the techniques of adaptive hydraulics, sensor, optic and auditory biological feedback, and signal processing were applied to this machine. The training system mainly consists of mechanical parts (including the chair of flexion and extension, the chair of right and left lateral flexion, the components of hydraulics and torque transformer, etc.), and the software of signal processing and biological feedback. Eleven volunteers were selected for the experiments of neck isometric contractive exercises, three times a week for 6 weeks, where CVR training (flexion, extension, right, left lateral flexion) one time a week. The increase in relative strength of the neck (flexion, extension, left and right lateral flexion) was 70.8%, 83.7%, 78.6% and 75.2%, respectively after training. Results show that the strength of the neck can be increased safely, effectively and rapidly with NSE-1 neck training machine to perform neck training.