DLM-GelMA/tumor slice sandwich structured tumor on a chip for drug efficacy testing.

The in vitro recapitulation of tumor microenvironment is of great interest to preclinical screening of drugs. Compared with culture of cell lines, tumor organ slices can better preserve the complex tumor architecture and phenotypic activity of native cells, but are limited by their exposure to fluid shear and gradual degradation under perfusion culture. Here, we established a decellularized liver matrix (DLM)-GelMA "sandwich" structure and a perfusion-based microfluidic platform to support long-term culture of tumor slices with excellent structural integrity and cell viability over 7 days. The DLM-GelMA was able to secrete cytokines and growth factors while providing shear protection to the tumor slice via the sandwich structure, leading to the preservation of the tumor microenvironment where immune cells (CD3, CD8, CD68), tumor-associated fibroblasts (α-SMA), and extracellular matrix components (collagen I, fibronectin) were well maintained. Furthermore, this chip presented anti-tumor efficacy at cisplatin (20 µM) on tumor patients, demonstrating our platform's efficacy to design patient-specific treatment regimens. Taken together, the successful development of this DLM-GelMA sandwich structure on the chip could faithfully reflect the tumor microenvironment and immune response, accelerating the screening process of drug molecules and providing insights for practical medicine.

Audible Acoustic Wave Promotes EV Formation and Secretion from Adherent Cancer Cells via Mechanical Stimulation.

Cancer-derived extracellular vesicles (EVs) have shown great potential in the field of cancer metastasis research. However, inefficient EV biofabrication has become a barrier to large-scale research on cancer-derived EVs. Here, we presented a novel method to enhance the biofabrication of cancer-derived EVs via audible acoustic wave (AAW), which yielded mechanical stimuli, including surface acoustic pressure and surface stress. Compared to EV yield in conventional static culture, AAW increased the number of cancer-derived EVs by up to 2.5-folds within 3 days. Furthermore, cancer-derived EVs under AAW stimulation exhibited morphology, size, and zeta potential comparable to EVs generated in conventional static culture, and more importantly, they showed the capability to promote cancer cell migration and invasion under both 2D and 3D culture conditions. Additionally, the elevation in EV biofabrication correlated with the activation of the ESCRT pathway and upregulation of membrane fusion-associated proteins (RAB family, SNARE family, RHO family) in response to AAW stimulation. We believe that AAW represents an attractive approach to achieving high-quantity and high-quality production of EVs and that it has the potential to enhance EV biofabrication from other cell types, thereby facilitating EV-based scientific and translational research.

Effects of HepaSphere microsphere encapsule epirubicin with a new loading method transarterial chemoembolization: in vitro and in vivo experiments.

METHODS: HS microspheres were loaded in a solution of hypertonic saline and contrast medium at different ratios. Morphology, size distribution, and drug loading capacity of the microsphere were evaluated. Rabbits with hepatic VX2 tumors underwent conventional TACE, drug-eluting beads TACE with HS microsphere loading epirubicin by recommended method (dTACE) or a new loading method (ndTACE). The plasma and tissue epirubicin concentration, tumor necrosis, and the microsphere distribution within the tumor were assessed. RESULTS: It was found that the mean diameter of HS microspheres was effectively reduced to 102 ± 14 µm after loading with 10.0% NaCl and Ultravist (370 mg I /mL) at a ratio of 2: 8 ml. The loading capacity reached 78.7%. It was noted that the concentration of tumor epirubicin was significantly higher (p = 0.016) in the ndTACE group (11,989.8 ± 5776.6 ng/g) than the concentration in the dTACE (6516.5 ± 3682.3 ng/g) and in cTACE groups (1564.1 ± 696.1 ng/g, p < 0.001). Further, the tumor necrosis in group with the new loading method (ndTACE) was 92.4%. CONCLUSIONS: The size of HS microsphere can be effectively reduced when it is loaded with a mixture of hypertonic saline and non-ionic contrast material. HS microsphere loaded with epirubicin using the new method (ndTACE) can increase the drug concentration in tumor and hence exert better improved antitumor effect.

A biomimetic renal fibrosis progression model on-chip evaluates anti-fibrotic effects longitudinally in a dynamic fibrogenic niche.

Although renal fibrosis can advance chronic kidney disease and progressively lead to end-stage renal failure, no effective anti-fibrotic drugs have been clinically approved. To aid drug development, we developed a biomimetic renal fibrosis progression model on-chip to evaluate anti-fibrotic effects of natural killer cell-derived extracellular vesicles and pirfenidone (PFD) across different fibrotic stages. First, the dynamic interplay between fibroblasts and kidney-derived extracellular matrix (ECM) resembling the fibrogenic niche on-chip demonstrated that myofibroblasts induced by stiff ECM in 3 days were reversed to fibroblasts by switching to soft ECM, which was within 2, but not 7 days. Second, PFD significantly down-regulated the expression of α-SMA in NRK-49F in medium ECM, as opposed to stiff ECM. Third, a study in rats showed that early administration of PFD significantly inhibited renal fibrosis in terms of the expression levels of α-SMA and YAP. Taken together, both on-chip and animal models indicate the importance of early anti-fibrotic intervention for checking the progression of renal fibrosis. Therefore, this renal fibrosis progression on-chip with a feature of recapitulating dynamic biochemical and biophysical cues can be readily used to assess anti-fibrotic candidates and to explore the tipping point when the fibrotic fate can be rescued for better medical intervention.

Quality-Achieving Reliability Assessment of Rolling Bearing Based on Bootstrap Maximum Entropy Method and Similarity Method.

Rolling bearing reliability is often affected by the processing quality, however the life reliability or operating reliability do not involve the study of rolling bearing processing quality assessment. In order to avoid bearing failure caused by bearing processing quality, it is necessary to evaluate the reliability of the bearing quality assurance capability. The difficulty in reliable evaluation of bearing's quality assurance capability is how to quantify the uncertain relationships between the bearing quality and its influence factors, and then determine the weight of different influencing factors. Therefore, in this paper, a novel method for determining the weight of bearing quality-influencing factors based on bootstrap maximum entropy method and similarity method is proposed, and then the quality-achieving reliability model is established. The experimental results show that the proposed method can effectively quantify the relationship between the bearing quality and its influencing factors, and accurately assess the bearing quality assurance capability and bearing quality processing level under the condition of a small number of experimental bearings. Compared with other quality-achieving reliability method, the proposed method is more effective.

Identification of Epithelial Mesenchymal Transition-Related lncRNAs Associated with Prognosis and Tumor Immune Microenvironment of Hepatocellular Carcinoma.

PURPOSE: The long noncoding RNAs (lncRNAs) play the important role in tumor occurrence and progression, and the epithelial to mesenchymal transition (EMT) is the critical process for tumor migration. However, the role of EMT-related lncRNA in hepatocellular carcinoma (HCC) has not been elucidated. METHODS: In this study, we selected the EMT-related lncRNAs in HCC by using data from The Cancer Genome Atlas database (TCGA). Two prognostic models of the overall survival (OS) and relapse-free survival (RFS) were constructed and validated through Cox regression model, Kaplan-Meier analysis, and the receiver-operating characteristic (ROC) curves. The unsupervised clustering analysis was utilized to investigate the association between EMT-lncRNAs with tumor immune microenvironment. ESTIMATE algorithm and gene set enrichment analysis (GSEA) were used to estimate tumor microenvironment and associated KEGG pathways. RESULTS: Two EMT-related lncRNA prognostic models of OS and RFS were constructed. Kaplan-Meier curves showed the dismal prognosis of OS and RFS in the group with high-risk score. The ROC curves and AUC values in two prognostic models indicated the discriminative value in the training set and validation set. Patients with HCC were clustered into two subgroups according the unsupervised clustering analysis. Lnc-CCNY-1 was selected as the key lncRNA. GSVA analysis showed that lnc-CCNY-1 was negatively associated with peroxisome proliferator-activated receptor (PPAR) signaling pathway and positively correlated with CELL cycle pathway. CONCLUSION: Two EMT-related lncRNA prognostic models of OS and RFS were constructed to discriminate patients and predict prognosis of HCC. EMT-related lncRNAs may play a role on prognosis of HCC by influencing the immune microenvironment. Lnc-CCNY-1 was selected as the key EMT-related lncRNA for further exploration.

RGB Color Model Analysis for a Simple Structured Polydimethylsiloxane Pneumatic Micromixer.

This article reports mixability experiments and their RGB color model analysis for a simple structured micromixer based on the pneumatic-driven membrane in multiple microreagent mixing applications. First, a novel and simple structure consisting of a mixing chamber and a pneumatic chamber is designed and fabricated of polydimethylsiloxane (PDMS) material, which facilitates integration with microfluidic chips. Then, experiment results and their RGB color model about mixing efficiency are investigated. Compared with conventional methods, the RGB color model for mixing results is easy and intuitive. In addition, the designed micromixer operation relies on less external laboratory infrastructure because of its simple structure.

MIR210HG regulates glycolysis, cell proliferation, and metastasis of pancreatic cancer cells through miR-125b-5p/HK2/PKM2 axis.

Pancreatic cancer has the worst prognosis of all common cancers. Pancreatic cancer cells have a metabolic advantage due to their swiftly adaptive responses to hypoxic and low-nutrient medium. This advantage contributes to the aggressivity of pancreatic cancer. In this study, lncRNA MIR210HG was abnormally upregulated within pancreatic cancer. It acted as a key oncogenic regulator of pancreatic cancer aggressiveness and glycolysis. Knockdown of MIR210HG significantly inhibited the aggressive phenotype of pancreatic cancer cells and inhibited the growth of xenograft tumours. More importantly, MIR210HG knockdown inhibited pancreatic cancer cell glycolysis via regulating the glycolysis-related hexokinase 2 (HK2) and Pyruvate kinase muscle isozyme M2 (PKM2) expression. Compared with the MIR210HG knockdown group, miR-125b-5p inhibition promoted the aggressive phenotypes and glycolysis of pancreatic cancer cells. Furthermore, the effects of MIR210HG knockdown on HK2 and PKM2 expression, pancreatic cancer cell aggressive phenotypes, and glycolysis were significantly reversed by miR-125b-5p inhibition. In tissue samples, MIR210HG expression was negatively correlated with miR-125b-5p levels and positively correlated with HK2 and PKM2 expression. miR-125b-5p expression was negatively correlated with HK2 and PKM2 expression. In conclusion, MIR210HG affected the phenotypes of pancreatic cancer cells, including proliferation, invasion, migration, and glycolysis, via modulating the miR-125b-5p/HK2/PKM2 axis.

An iodine-125 seed strand combined with a metal stent versus a metal stent alone for obstructive jaundice caused by pancreatic ductal adenocarcinoma.

PURPOSE: The purpose of this study was to assess the efficacy of an iodine-125 (125I) seed strand combined with a metal stent compared with a metal stent for treatment of obstructive jaundice caused by pancreatic ductal adenocarcinoma (PDAC). METHODS AND MATERIALS: A retrospective analysis was carried out of patients who were referred to Shanghai Zhongshan Hospital of Fudan University with a diagnosis of PDAC between January 1, 2010 and January 31, 2019. A total of 110 consecutive patients with obstructive jaundice caused by PDAC were divided into the iodine-125 seed strand combined with a metal stent group (Group A = 48) and the metal stent group (Group B = 62). The primary outcome was stent obstruction-free survival time, and secondary outcomes were overall survival and complications. RESULTS: The median stent obstruction-free survival time was 133.0 (95% confidence interval (CI): 166.093-149.907) days, and the median overall survival was 212.0 (95% CI: 187.183-236.817) days in all patients. Median stent obstruction-free survival time was 175 days (95% CI 103.165-246.835 days) in Group A versus 120 days (95% CI 87.475-152.525 days) in Group B (p = 0.035). A lower Eastern Cooperative Oncology Group (ECOG) score (p = 0. 000) and iodine-125 seed strand combined with metal stent implantation (p = 0.008) were associated with a longer stent obstruction-free survival time. Obstruction length (p = 0.083), ECOG score (p = 0.000), and iodine-125 seeds (p = 0.037) might have potential impact on stent obstruction-free survival time and were included for multivariable analysis using the Cox proportional hazards model. Stent restenosis was observed in 18.8% (9/48) of patients in Group A and 54.8% (34/62) in Group B, respectively. There was no significant difference in median survival between Group A and Group B (p = 0.409). The median survival in Group A was 209 days (95% CI 150.750-267.250) and 202 days (95% CI 190.624-233.376) in Group B. The median survival of patients with a lower ECOG score was better than that of patients with a higher ECOG score (267 days vs 132 days, p = 0.000). The Grade 3 or 4 complications occurred in 4 (8.3%) of the 48 patients in Group A (one case of hemobilia, one case of liver abscess, two cases of choleperitonitis) and in 5 (8.1%) of the 62 patients in Group B (one case of hemobilia, two cases of liver abscess, two cases of choleperitonitis) (p = 0.972). CONCLUSIONS: Implantation of an iodine-125 seed strand combined with a metal stent provides longer obstruction-free survival time compared with a metal stent in patients with obstructive jaundice caused by PDAC. It seems reasonable to choose an iodine-125 seed strand combined with a metal stent as a treatment for these patients.

Percutaneous intraductal radiofrequency ablation combined with biliary stent placement for treatment of malignant biliary obstruction.

PURPOSE: To determine the safety and efficacy of percutaneous intraductal radiofrequency ablation (RFA) combined with biliary metal stent placement for patients with unresectable malignant biliary obstruction. METHODS: From a cohort of 70 patients with unresectable malignant biliary obstruction, 28 patients received percutaneous intraductal RFA combined with biliary stent placement (group A) and the remaining 42 were treated with biliary metal stent placement only (group B). Stent patency, overall survival (OS), alleviation of jaundice, and postoperative complications were assessed. RESULTS: The technical success rate for both groups was 100%. No severe complications (e.g., biliary bleeding, perforation) occurred. In both groups, jaundice was relieved and the decrease of the total and direct bilirubin concentration was significant (p < 0.01). The median time of stent patency in group A and group B were 6.6 ± 0.3 months (95% CI 6.1-7.1 months) and 4.9 ± 0.4 months (95% CI 4.2-5.6 months), respectively (p < 0.01). The median overall survival times in Group A were 7.2 ± 0.3 months (95% CI 6.5-7.9 months) versus 5.6 ± 0.4 months (95% CI 4.8-6.4 months) in group B (p < 0.01). In univariate and multivariate analyses, intraductal RFA, stent patency, and decreased baseline serum direct bilirubin concentration were associated with greater OS (p < 0.05). CONCLUSION: Percutaneous intraductal RFA combined with stent placement is a safe and effective method for patients with malignant biliary obstruction. As compared to stent placement alone, percutaneous intraductal RFA can significantly prolong stent patency and improve the overall survival of patients with malignant biliary obstruction.

Simulation Analysis of the Aerodynamic Performance of a Bionic Aircraft with Foldable Beetle Wings in Gliding Flight.

Beetles have excellent flight performance. Based on the four-plate mechanism theory, a novel bionic flapping aircraft with foldable beetle wings was designed. It can perform flapping, gliding, wing folding, and abduction/adduction movements with a self-locking function. In order to study the flight characteristics of beetles and improve their gliding performance, this paper used a two-way Fluid-Structure Interaction (FSI) numerical simulation method to focus on the gliding performance of the bionic flapping aircraft. The effects of elastic model, rigid and flexible wing, angle of attack, and velocity on the aerodynamic characteristics of the aircraft in gliding flight are analyzed. It was found that the elastic modulus of the flexible hinges has little effect on the aerodynamic performance of the aircraft. Both the rigid and the flexible wings have a maximum lift-to-drag ratio when the attack angle is 10°. The lift increased with the increase of the gliding speed, and it was found that the lift cannot support the gliding movement at low speeds. In order to achieve gliding, considering the weight and flight performance, the weight of the microair vehicle is controlled at about 3 g, and the gliding speed is guaranteed to be greater than 6.5 m/s. The results of this study are of great significance for the design of bionic flapping aircrafts.

Conceptual Design and Computational Modeling Analysis of a Single-Leg System of a Quadruped Bionic Horse Robot Driven by a Cam-Linkage Mechanism.

In this study, the configuration of a bionic horse robot for equine-assisted therapy is presented. A single-leg system with two degrees of freedom (DOFs) is driven by a cam-linkage mechanism, and it can adjust the span and height of the leg end-point trajectory. After a brief introduction on the quadruped bionic horse robot, the structure and working principle of a single-leg system are discussed in detail. Kinematic analysis of a single-leg system is conducted, and the relationships between the structural parameters and leg trajectory are obtained. On this basis, the pressure angle characteristics of the cam-linkage mechanism are studied, and the leg end-point trajectories of the robot are obtained for several inclination angles controlled by the rotation of the motor for the stride length adjusting. The closed-loop vector method is used for the kinematic analysis, and the motion analysis system is developed in MATLAB software. The motion analysis results are verified by a three-dimensional simulation model developed in Solidworks software. The presented research on the configuration, kinematic modeling, and pressure angle characteristics of the bionic horse robot lays the foundation for subsequent research on the practical application of the proposed bionic horse robot.

Research on an Ankle Joint Auxiliary Rehabilitation Robot with a Rigid-Flexible Hybrid Drive Based on a 2-S'PS' Mechanism.

An ankle joint auxiliary rehabilitation robot has been developed, which consists of an upper platform, a lower platform, a dorsiflexion/plantar flexion drive system, a varus/valgus drive system, and some connecting parts. The upper platform connects to the lower platform through a ball pin pair and two driving branch chains based on the S'PS' mechanism. Although the robot has two degrees of freedom (DOF), the upper platform can realize three kinds of motion. To achieve ankle joint auxiliary rehabilitation, the ankle joint of patients on the upper platform makes a bionic motion. The robot uses a centre ball pin pair as the main support to simulate the motion of the ankle joint; the upper platform and the centre ball pin pair construct a mirror image of a patient's foot and ankle joint, which satisfies the human body physiological characteristics; the driving systems adopt a rigid-flexible hybrid structure; and the dorsiflexion/plantar flexion motion and the varus/valgus motion are decoupled. These structural features can avoid secondary damage to the patient. The rehabilitation process is considered, and energy consumption of the robot is studied. An experimental prototype demonstrates that the robot can simulate the motion of the human foot.

Precise localization of small pulmonary nodules using Pre-VATS with Xper-CT in combination with real-time fluoroscopy-guided coil: report of 15 patients.

Purpose: This study aimed to evaluate the value of precise localization of nodules using pre-video-assisted thoracic surgery (VATS) Xper-CT in combination with real-time fluoroscopy-guided coil in the resection of pulmonary nodules using VATS. Materials and Methods: Precise localization of nodules using Xper-CT in combination with real-time fluoroscopy-guided coil and wedge resection using VATS were conducted on 15 patients with 17 small pulmonary nodules (diameter 0.5-1.5 cm) from April 2015 to January 2016. The value of localization was evaluated in terms of procedure time, type of coils, associated complications of localization, and VATS success rate. Results: The success rate of coil localization was found to be 100% in the primary stage (as shown by the CT scan), and the average procedure time was 30-45 min (35.6 ± 3.05 min). No deaths or major complications occurred. Minor complications included five incidents of pneumothorax (the morbidity was 29.4%, 5/17; no patient required chest tube drainage). The dislocation of coil was found in one patient. The results of pathological examination of 17 small pulmonary nodules revealed 11 primary lung cancers, 1 mesenchymal tumor, 3 nonspecific chronic inflammations, 1 hamartoma, and 1 tuberculosis. Two patients with primary lung cancer underwent lobectomy with mediastinal lymph node dissection. Conclusion: The preoperative precise localization of small pulmonary nodules using Xper-CT-guided coil is an effective and safe technique. It helps in the resection of nodules using VATS. It increases the rate of lung wedge resection with few complications and allows for proper diagnosis with a low thoracotomy conversion rate.

Increased risk of hepatocellular carcinoma in patients with diabetes mellitus: a systematic review and meta-analysis of cohort studies.

In recent years, increasing evidence has suggested a strong association between diabetes mellitus (DM) and hepatocellular carcinoma (HCC). To provide a quantitative assessment of this association, we performed a systematic review and meta-analysis of cohort studies. We collected studies through a literature search of Medline from January 1, 1966 and EMBASE from January 1, 1974, through July 31, 2010. Summary relative risks (SRRs) with their corresponding 95% confidence intervals (CIs) were calculated using a random-effects model. A total of 25 cohort studies that met our inclusion and exclusion criteria were included in our analysis. Among these, 18 studies showed that DM was associated with an increased incidence of HCC (SRRs = 2.01, 95% CI: 1.61-2.51), compared with individuals without DM. There was a statistically significant heterogeneity among these studies (Q = 136.68, p < 0.001, I(2) = 87.6%). Analyses subgrouped by controlling confounders revealed that the increased incidence of HCC was independent of geographic location, alcohol consumption, history of cirrhosis, or infections with hepatitis B (HBV) or hepatitis C virus (HCV). In addition, DM was also positively associated with HCC mortality (SRR = 1.56; 95% CI: 1.30-1.87), with no significant evidence of heterogeneity among studies (Q = 1.16, p = 0.56, I(2) =0%). There were no significant publication bias (p = 0.79 for Egger's regression asymmetry test). These findings strongly support a positive association between DM and increased risk of HCC in both males and females.