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Restenosis after stent implantation is a major limitation of revascularization technique. Retrieving the stent safely and smoothly after the vascular remodeling is completed shows important clinical value. In this paper, a novel retrievable peripheral vascular stent and its modified retrieval platform were developed and a finite element analysis (FEA) model was established to study the retrieval process of the stent. Meanwhile, the safety and feasibility of the retrievable stent were assessed through in vivo experiments. The maximum strain of the stent is 6.87% during the whole retrieval process, which is less than the ultimate elastic strain of nitinol alloy. The simulation results indicate that the stent is not damaged during the whole retrieval process. Finally, the stents were implanted into Bama miniature pigs to assess the retrieval process, and the results suggest that the stents can be retrieved successfully within 30 min after implantation, and minor local mechanical injury can be found in the intimal layer of the blood vessel due to the deployment and retrieval of the stent. Studies presented in this work illustrate the feasibility of a novel retrievable peripheral vascular stent, providing an additional avenue to reduce the risk of restenosis.

Purpose Design, fabricate and evaluate all-solid-state wearable sensor systems that can monitor ion concentrations in human sweat to provide real time health analysis and disease diagnosis capabilities. Design/methodology/approach A human health monitoring system includes disposable customized flexible electrode array and a compact signal transmission-processing electronic unit. Findings Patterned rGO (reduced-graphene oxide) layers can replace traditional metal electrodes for the fabrication of free-standing all solid film sensors to provide improved flexibility, sensitivity, selectivity, and stability in ion concentration monitoring. Electrochemical measurements show the open circuit potential of current selective electrodes exhibit near Nernst responses versus Na+ and K+ ion concentration in sweat. These signals show great stability during a typical measurement period of 3 weeks. Sensor performances evaluated through real time measurements on human subjects show strong correlations between subject activity and sweating levels, confirming high degree of robustness, sensitivity, reliability and practicality of current sensor systems. Originality/value In improving flexibility, stability and interfacial coherency of chemical sensor arrays, rGO films have been the developed as a high-performance alternative to conventional electrode with significant cost and processing complexity reduction. rGO supported solid state electrode arrays have been found to have linear potential response versus ion concentration, suitable for electrochemical sensing applications. Current sweat sensor system has a high degree of integration, including electrode arrays, signal processing circuits, and data visualization interfaces.

Radiofrequency (RF)-induced tissue fusion shows great potential in sealing intestinal tissue without foreign materials. To improve the performance of RF-induced tissue fusion, a novel self-cooling jaw has been designed to minimize thermal damage during the fusion.The prototype of self-cooling jaws was developed and manufactured. A total number of 60 mucosa-to-mucosa fusions were conducted usingThe self-cooling jaws showed significant decrease in temperature during the fusion process. An optimal burst pressure (5.7 ± 0.5 kPa) and thermal damage range (0.9 ± 0.1 mm) were observed when the applied RF power was 100 W. The thermal damage range of the prototype has almost decreased 36% in comparison with the conventional bipolar jaws (1.4 ± 0.1 mm). The histological observation revealed that a decrease of thermal damage was achieved through the application of self-cooling jaws.The self-cooling jaws were proved to be effective for reducing the thermal damage during RF-induced tissue fusion, which could potentially promote the clinical application of tissue fusion techniques in the future.

DNA is well-documented to stimulate immune response. However, the nature of the DNA to activate immune surveillance is less understood. Here, we show that the activation of cyclic GMP-AMP synthase (cGAS) depends on DNA mechanical flexibility, which is controlled by DNA-sequence, -damage and -length. Consistently, DNA-sequence was shown to control cGAS activation. Structural analyses revealed that a conserved cGAS residue (mouse R222 or human R236) contributed to the DNA-flexibility detection. And the residue substitution neutralised the flexibility-controlled DNA-potential to activate cGAS, and relaxed the DNA-length specificity of cGAS. Moreover, low dose radiation was shown to mount cGAS-mediated acute immune surveillance (AIS) via repairable (reusable) DNAs in hrs. Loss of cGAS-mediated AIS decreased the regression of local and abscopal tumours in the context of focal radiation and immune checkpoint blockade. Our results build a direct link between immunosurveillance and DNA mechanical feature.

Colorectal cancer is a common malignant tumor in the gastrointestinal tract. Resection of the cancerous site and anastomosis of the residual intestine is the preferred radical treatment for colorectal cancer. In particular, radio frequency energy anastomosis of the residual intestine is being increasingly used in clinical practice. To improve the quality of anastomosis, reduce the thermal damage of tissue near the anastomosis area, and avoid foreign body residue in this area, we propose a self-cooling eversion-type radio frequency-energy intestinal anastomosis electrode, which is analyzed through simulations and evaluated experimentally for welding intestinal tissue. For radio frequency energy power of 160 W, anastomosis time of 13.2 s, and pressure of 154 kPa, the disconnected intestinal tissues can be anastomosed using the proposed electrode. The average burst pressure of the anastomotic orifice is 43.86 mmHg. During welding, the temperature of the normal saline at the outlet is 6.8 °C higher than that at the inlet, indicating that the use of circulating normal saline as the conductive and cooling medium can dissipate part of the heat generated by welding and reduce heat accumulation, thereby reducing thermal damage of biological tissue near the welding area. Overall, the proposed electrode may contribute to the recovery of postoperative intestinal function by enabling a novel strategy for clinical intestinal anastomosis induced by radio frequency energy.

Mitochondrial DNA (mtDNA) variations have been implicated in various cancer types. Several attempts have been made in benign parathyroid adenoma (PA); however, mtDNA variants and copy number alterations have not been investigated in parathyroid carcinoma (PC). The present study aimed to explore the variations in the mitochondrial genome in parathyroid neoplasms. In this study, ultradeep targeted sequencing of mtDNA was performed in 12 cases with PC and 25 cases with PA. Germline and somatic variants in the mitochondrial genome were analysed according to clinical features. The mtDNA copy number relative to nuclear DNA was measured. A total of 821 germline variants and 23 somatic mutations were identified. All 160 germline nonsynonymous variants in the coding sequence (CDS) were predicted to be likely benign, and germline variants frequently occurred (26.3%) in the displacement loop region. Tumour somatic mutation in a CDS with heteroplasmic factor (HF) >0.8 showed a higher mtDNA copy number (p = 0.039). Using Spearman’s rank test, tumour mtDNA copy number revealed a positive correlation with serum levels of intact parathyroid hormone and calcium. Our results demonstrate that null recurrent mtDNA mutational hotspots were PC specific. An increased mtDNA copy number in parathyroid neoplasms was associated with somatic CDS mutations with a high HF and major clinical features. Larger cohort investigations should be performed in future analyses.

A novel endoscopic multi-firing clip applicator (EMFCA) system was developed for closing large perforations, in which the clips was deployed by pushing through a tendon-sheath actuation system (TSAS). However, the closure performance is heavily dependent on the pushing force transmitted to the clips which shows different nonlinear characteristics comparing with pulling transmission. Therefore, this study aimed to develop a pushing transmission model of the TSAS for precise control of the EMFCA, and verify its applicability. A pushing transmission model of the TSAS was proposed and simulated. Meanwhile, a TSAS-based push-transmission platform was designed to identify the parameters which potentially affect the transmission efficiency. Besides, ex vivo endoscopic stomach perforation closure experiments were carried out with the EMFCA system to validate the reliability of the proposed model. The experiment indicated that the results of simulation had a satisfactory agreement with the experimental data. The force and displacement transmission presented a linear relationship during the loading and unloading period, and the transmission efficiency and dead zone were affected by the tendon-sheath diameter ratio and the curvature. The ex-vivo testing revealed that a superior closure was obtained by using the EMFCA through effective deformation of the clip to anchor loop tightly onto the tissue when the input forces were in the range of 21–30 N. The proposed pushing transmission model could provide a reliable prediction of force feedback which contributes to accuracy control of the flexible endoscopic instrument with TSAS and improving the safety of endoscopic surgery.

Biological soft tissues manipulation, including conventional (mechanical) and nonconventional (laser, waterjet and ultrasonic) processes, is critically required in most surgical innervations. However, the soft tissues, with their nature of anisotropic and viscoelastic mechanical properties, and high biological and heat sensitivities, are difficult to manipulated. Moreover, the mechanical and thermal induced damage on the surface and surrounding tissue during the surgery can impair the proliferative phase of healing. Thus, understanding the manipulation mechanism and the resulted surface damage is of importance to the community. In recent years, more and more scholars carried out researches on soft biological tissue cutting in order to improve the cutting performance of surgical instruments and reduce the surgery induced tissue damage. However, there is a lack of compressive review that focused on the recent advances in soft biological tissue manipulating technologies. Hence, this review paper attempts to provide an informative literature survey of the state-of-the-art of soft tissue manipulation processes in surgery. This is achieved by exploring and recollecting the different soft tissue manipulation techniques currently used, including mechanical, laser, waterjet and ultrasonic cutting and advanced anastomosis and reconstruction processes, with highlighting their governing removal mechanisms as well as the surface and subsurface damages.

This paper reports the design of a powered stapler for gastrointestinal anastomosis and evaluates its performance. The proposed stapling instrument is intended to simplify and optimize the current procedure of mechanical stapling, while providing controllable operation for the powered stapling procedure, such as conditioning the tissue to the right stage before firing of the stapler.The feasibility and efficacy of the prototype were assessed byThe functionality of the developed powered stapler was validated, where the theoretical, numerical, and experimental results agree well with each other. The preliminary results indicated that the proposed tissue conditioning operation could lower the clamping pressure with a maximum level of 1.35 g/mmThe developed novel tissue conditioning procedure could reduce the pressure response of the intestine tissue samples. The proposed powered stapler proves effective for performing gastrointestinal anastomosis procedures.

Objective. Motion analysis of surgical instruments can be used to evaluate laparoscopic surgical skills, and this study assessed the validity of an optical tracking system for the assessment of laparoscopic surgical motor skills. Methods. Ten experienced surgeons and ten novices were recruited to complete the transferring tasks on a laparoscopic simulator. An optical tracking system, Micron Tracker, was used to capture the marker points on each instrument and to obtain the coordinates of the marker points and the corresponding instrument tip coordinates. The data are processed to create a coordinate system based on the laparoscopic simulator and to calculate the movement parameters of the instruments, such as operating time, path length, speed, acceleration, and smoothness. At the same time, the range of motion of the instrument (insertion depth and pivoting angle) is also calculated. Results. The position that the tip of the instrument can reach is a small, irregularly shaped spatial area. Significant differences ( p < 0.05 ) were found between the surgeon and novice groups in parameters such as operating time, path length, mean speed, mean acceleration, and mean smoothness. The range of insertion depth of the instruments was approximately 150 mm to 240 mm, and the pivoting angles of the left and right instruments were 30.9° and 46.6° up and down and 28.0° and 35.0° left and right, respectively. Conclusions. The optical tracking system was effective in subjectively evaluating laparoscopic surgical skills, with significant differences between the surgeon and novice groups in terms of movement parameters, but not in terms of range of motion.

The mechanism of chemo-resistance in small cell lung cancer (SCLC) is unclear. This study aims to explore the resistance-related genomic profiles of residual tumors after neo-adjuvant chemotherapy (NAC) in SCLC through the whole-exome sequencing (WES).A total of 416 limited diseases (LD) SCLC patients underwent surgery were retrospectively analyzed, of which 40 patients received NAC. Then we selected 29 patients undergoing NAC (n = 19) and chemotherapy naïve (CTN, n = 10) to perform WES sequence with formalin-fixed paraffin-embedded samples including tumor and paired para-tumor.In total, single nucleotide variation and mutation rate were similar between NAC and CTN groups. The mutation signatures were significantly discrepant between NAC and CTN groups, as well as among patients with partial response (PR), stable disease (SD), and progressive disease. There were more copy number variation deletions in NAC group compared with CTN group. The inactivation of TP53 and RB1 were the most significantly events in both NAC and CTN groups. RB1 nonsense mutations were recurrent in NAC group (9/19 vs. 0/9, 47.4% vs. 0%) with favorable survival, while the frame-shift deletions were frequent in CTN group (3/9 vs. 3/19, 33.3% vs.15.8%). Integrated function enrichment revealed that the frequently mutant genes were involved in cell cycle, metabolic reprogramming, and oncogenic signaling pathways in NAC group, such as BTG2 pathway, glycolysis in senescence and P53 pathway. A total of 27 genes presented frequently mutant in NAC group and might played a positive role in drug resistance. Multiple genes including BRINP3, MYH6, ST18, and PCHD15, which were associated with prognosis, occurred mutant frequently in PR and SD groups.Residual tumors after neo-adjuvant therapy exhibited different mutation signature spectrum. Multiple genes including RB1 nonsense mutations, BRINP3, MYH6, ST18, and PCHD15 were with frequent mutation in residual tumors, which might participate chemo-resistance and influenced the prognosis in patients with limited disease SCLC.

The mechanical behavior of the ventricular septal defect (VSD) occluder is strongly linked to complications following transcatheter closure of the VSD. Methods: A mechanical model of the VSD occluder was constructed by theoretical modeling of the braiding structure. The mechanical properties of the VSD occluders with different braiding angles (30 deg, 45 deg, 60 deg), materials (nitinol (NiTi), polydioxanone (PDO)), and waist-heights (3 mm, 4 mm) were studied by finite element analysis and validated by bench tests. Under 1 mm radial shrinkage, the bending angles at the waist of the 30 deg NiTi, 45 deg NiTi, 60 deg NiTi and 45 deg PDO occluders were 112 deg, 121 deg, 155 deg and 155 deg, respectively. The maximum principal strains at the waist were 16.62%, 8.19%, 1.20%, and 0.66%, respectively. With 0.5 rad axial bending, the maximum radial deformations at the waist were 1.73, 1.44, 0.41 and 1.68 mm, respectively. When the occluders were implanted into VSD with the mean thickness of 3.5 mm, considerable stress developed at the hole's margin and the contact area. The area with the 3 mm occluder was much bigger than that with the 4 mm occluder. Conclusions: the 60 deg NiTi occluder showed better ability to fit the deformation of the defect than the other NiTi occluders, and the 45 deg PDO occluder performed better under compression conditions but poorly under bending conditions than the 45 deg NiTi occluder. The choice of the appropriate waist-height is beneficial to eliminate associative complication by reducing the contact stress.

We have developed a convenient chemical conversion method of preparing a Mg3(PO4)2 coating with a lamellar structure of about 1–5 μm width on Mg-Nd-Zn-Zr (denoted as JDBM) alloy, aiming to improve the corrosion resistance and biological response. The protective effect of the phosphate coating on JDBM alloy leads to an increase in corrosion resistance of about 25% from 0.337 ± 0.021 to 0.253 ± 0.047 mm y−1. A systematic study on in vitro cytocompatibility test shows that the phosphate coated JDBM has minimal negative effect on human umbilical vein endothelial cells (HUVECs) viability, growth and proliferation, and the coating also presents a favorable affinity for HUVECs by supporting higher adherent cell density and sufficient cell spreading. In addition, the investigation of in vitro hemocompatibility confirms reduced hemolysis ratio and excellent anti-platelet adhesion property of the phosphate coated JDBM. Furthermore, this study also presents our more recent efforts to develop an in-depth understanding of the mechanism which is involving anti-platelet adhesion on the surface of biodegradable Mg substrate.

Background and objectives The finite element method was used, and experiments were performed to analyze the effect of different electrode spacings and power combinations on the electrical and thermal aspects of biological tissues during bipolar radiofrequency (RF) fat dissolution. Through these efforts, this study also attempted to develop a reasonable electrode spacing and power combination that can achieve fat dissolution effects, the RF energy of which will not thermally damage the tissue. Study design/materials and methods COMSOL was adopted to conduct a finite element analysis for bio-thermoelectric coupling, and a two-dimensional time-domain model of biological tissue was built. A self-developed single-channel bipolar RF device was employed to load RF energy on the ex vivo porcine abdominal tissue. The thermal characteristics of the tissue were characterized and analyzed with a thermal imager and thermocouple probes. Results Under a power of 5 W combined with the electrode spacings of 1, 2, and 3 cm, the temperature in the tissue could not reach that required for fat dissolution. Under a power of 15 W combined with the electrode spacings of 1, 2, and 3 cm, the RF energy would thermally damage part of the skin areas. Besides this, the combination of a power of 10 W and the electrode spacing of 1 cm would thermally damage the skin areas. The combination of a power of 10 W and the electrode spacing of 2 or 3 cm made part of the fat layer of the tissue satisfy the requirements of fat dissolution, and the fat dissolution area caused by the former was 118% larger than that of the latter; in the meantime, no heat damage to the skin layer was found. Conclusion Different electrode spacings and power combinations significantly affect the electrical and thermal properties of bipolar RF energy loaded on biological tissue, a reasonable electrode spacing and power combination is one of the critical factors leading to the success of bipolar RF fat dissolution. Lasers Surg. Med. © 2020 Wiley Periodicals, Inc.

Knowing the course of Alzheimer’s disease is very important to prevent the deterioration of the disease, and accurate segmentation of sensitive lesions can provide a visual basis for the diagnosis results. This study proposes an improved end-to-end dual-functional 3D convolutional neural network for segmenting bilateral hippocampi from 3D brain MRI scans and diagnosing AD progression states simultaneously. The proposed neural network is based on the V-Net and adopts an end-to-end structure. In order to relieve the excessive amount of convolutional parameters at the bottom of the V-Net, we change them to bottleneck architecture. Based on the segmentation network, we establish a classification network for diagnosing pathological states of brain. In order to balance the two tasks of hippocampi segmentation and brain pathological states diagnosis, we designed a unique loss function. This study included 132 samples, of which 100 were selected as training, and the remaining 32 were used to test the performance of our model. During training, we adopted fivefold cross-validation method. We selected the intersection over union and dice coefficient to evaluate the hippocampus segmentation performance, while the brain pathological states diagnosis performance was evaluated by accuracy, specificity, sensitivity, precision and F1 score. By using the proposed neural network, the left hippocampi segmentation Iou and dice coefficient reach 0.8240 ± 0.020 and 0.9035 ± 0.020, respectively. The right hippocampi Iou and dice coefficient reach 0.8454 ± 0.023 and 0.9162 ± 0.023, respectively. The accuracy, specificity, sensitivity, precision and F1 score of three-category classification of brain pathology are 84%, 92%, 84%, 86% and 85%, respectively. The proposed neural network has two functions of brain pathological states diagnosis and bilateral hippocampi segmentation with higher robustness and accuracy, respectively. The segmented bilateral hippocampi can be used as a reference for clinical decision making or intervention.

Epimedium brevicornu Maxim is a traditional Chinese medicinal plant with important value for curing several diseases, including liver cancer. Seed germination, field seedling emergence, and morphological and physiological traits were measured in developing seeds of E. brevicornu, which were collected at 7, 14, 21, 28, and 35 days after flowering. The results showed that with the fruit pericarp changing from lime green to dark red, the seed volume increased. Furthermore, the dry mass of seeds gradually increased from 0.011 g at 7 d to 0.275 g at 35 d, which was a significantly positive correlation with seed vigour (r = 0.980). The soluble protein content initially increased and then decreased to 11.09 mg/g and presented a maximum at 28 d; however, the soluble sugar content gradually declined to a minimum of 30.45 mg/g at 35 d, which was also significantly negatively correlated with seed vigour (r = −0.915). Furthermore, the unsaturated fatty acids (oleic acid and linoleic acid) increase with seed development. Abscisic acid (ABA) reached a maximum value of 18.45 ng/g at 28 d, and gibberellin (GA3), 3-Indoleacetic acid (IAA) and zeatin-riboside (ZR) initially increased and then decreased. These results suggest that the vigour of E. brevicornu seeds is closely associated with their stage of development, with the highest vigour observed at 28~35 d after flowering.

Endoscopic closure has become the first choice for closing iatrogenic perforations. Previously, we reported a self-developed endoscopic multifiring clip applicator (EMFCA) system. In this paper, a new EMFCA system for endoscopic closure of large perforations with a redesigned clip, the less traumatic grasper, and a highly efficient driving system was presented, and its efficacy was evaluated. The behaviors of the new clip and grasper were verified through finite element analysis (FEA). The capability of pushing transmission for the EMFCA system was identified by the proposed model and the validation experiment. Ex-vivo studies were conducted on porcine stomachs to compare the outcomes of the closures. The FEA results showed that the deformation of the clip was safe and smoother, with a maximum stress of 640.0 MPa. The less traumatic grasper could increase the grasping force and avoid trauma by exerting uniform stress along the axis. The capability of pushing transmission was enhanced by the double-nested tendon-sheath actuation system with an efficiency of 0.45–0.48. The mechanical strength, the leakage pressure, and the operating time for the closures with the new EMFCA system and the previous EMFCA system were 6.1 N ± 0.8 N, 37.1 mmHg ± 6.8 mmHg, 7.3 min ± 0.4 min and 5.1 N ± 1.0 N, 27.4 mmHg ± 6.4 mmHg, 11.4 min ±0.8 min, respectively. The new EMFCA system can realize a superior, reliable, and high-efficiency endoscopic closure of large perforations.

Due to overlapping tremor features, the medical diagnosis of Parkinson’s disease (PD) and essential tremor (ET) mainly relies on the clinical experience of doctors, which often leads to misdiagnosis. Seven predictive models using machine learning algorithms including random forest (RF), eXtreme Gradient Boosting (XGBoost), support vector machine (SVM), logistic regression (LR), ridge classification (Ridge), backpropagation neural network (BP), and convolutional neural network (CNN) were evaluated and compared aiming to better differentiate between PD and ET by using accessible demographics and tremor information of the upper limbs. The tremor information including tremor acceleration and surface electromyogram (sEMG) signals were collected from 398 patients (PD = 257, ET = 141) and then were used to train the established models to separate PD and ET. The performance of the models was evaluated by indices of accuracy and area under the curve (AUC), which indicated the ensemble learning models including RF and XGBoost showed the best overall predictive ability with accuracy above 0.84 and AUC above 0.90. Furthermore, the relative importance of sex, age, four postures, and five tremor features was analyzed and ranked showing that the dominant frequency of sEMG of flexors, the average amplitude of sEMG of flexors, resting posture, and winging posture had a greater impact on the diagnosis of PD, whereas sex and age were less important. These results provide a reference for the intelligent diagnosis of PD and show promise for use in wearable tremor suppression devices.

Targeting DNA repair pathway offers an important therapeutic strategy for cancers. However, the failure of DNA repair inhibitors to markedly benefit patients necessitates the development of new strategies. Here, we show that exosome component 1 (EXOSC1) promotes DNA damages and sensitizes kidney renal clear cell carcinoma (KIRC) cells to DNA repair inhibitor. Considering that endogenous source of mutation (ESM) constantly assaults genomic DNA and likely sensitize cancer cells to the inhibitor, we first analyzed the statistical relationship between the expression of individual genes and the mutations for KIRC. Among the candidates, EXOSC1 most notably promoted DNA damages and subsequent mutations via preferentially cleaving C site(s) in single-stranded DNA. Consistently, EXOSC1 was more significantly correlated with C>A transversions in coding strands than these in template strands in KIRC. Notably, KIRC patients with high EXOSC1 showed a poor prognosis, and EXOSC1 sensitized cancer cells to poly(ADP-ribose) polymerase inhibitor. These results show that EXOSC1 acts as an ESM in KIRC, and targeting EXOSC1 might be a potential therapeutic strategy.

In order to study the thermal stability of coated carbonyl iron powder (CIP) and its influence on magnetic properties, carbonyl iron powder was coated with a silica layer and then annealed in an air atmosphere at elevated temperatures. Transmission electron microscopy (TEM) analysis and Fourier transform infrared spectroscopy confirmed the existence of a silicon dioxide layer with a thickness of approximately 80~100 nm. Compared with uncoated CIP, the silicon-coated CIP still maintained a higher absorption performance after annealing, and the calculated impedance matching value Z only slightly decreased. It is worth noting that when the annealing temperature reached 300 °C, coercivity (Hc) increased, and the real and imaginary parts of the permeability decreased, which means that the silicon dioxide layer began to lose its effectiveness. On the contrary, the significant decrease in microwave absorption ability and impedance matching value Z of uncoated CIP after annealing were mainly because the newly formed oxide on the interface became the active polarization center, leading to an abnormal increase in permittivity. In terms of the incremental mass ratio after annealing, 2% was a tipping point for permeability reduction.

Structurally retrievable drug-eluting stents may have valuable clinical applications because they do not leave any foreign materials inside the patient's body. This article presents a novel design of retrievable peripheral vascular stent and the results from biomechanical analysis of its performance. Using the finite element analysis method, principal parameters of the stent were studied. Moreover, to ensure the practicability of the retrieval process, simulation, and in vitro experiments were performed. The retrieval force reached the maximum value when the whole retrievable part had been retrieved. Furthermore, the force was gradually increased during the retrieval process and remained constant after the main part had been retrieved. When the stent was being compressed, the maximum strain of the stent occurred at the connection between the stent's retrieval part and the main body part, at a value of 4%. The index of nonuniformity of the stent was too small to be counted both at the end of the compression and self-expansion processes. With the increase of moment, the bending stiffness (EI) of the stent decreased gradually. After bending moment was applied, the large strain region was mainly located in the stent's main body part rather than the retrieval part. The results of preliminary stent retrieval experiments demonstrated that the stent could be retrieved successfully. This novel retrievable stent displays promising biomechanical performance. The preliminary experiments demonstrated that the stent could be retrieved smoothly from the blood vessels.

In this study, numerical simulation and physical experiments are carried out to investigate the influence of material surface microstructure on its hydrophobicity. By observing the contact angle and liquid phase state of the droplet on various morphological surfaces, the relationship between the size and morphology of microstructures and the hydrophobicity of material surface is explored. The influence of microstructure on the hydrophobicity is reflected by:1. changes of the contact angle along with the changes of microstructure size, 2. anisotropy of liquid droplet spreading along with the changes of wire groove and cylindrical morphology. Driven by tension, droplets can move spontaneously on the surface of specific microstructures, and the moving speed and direction vary with the distribution of the microstructures.

Purpose: A control algorithm for radio-frequency-induced intestinal tissue fusion was developed to explore the effects of different control parameters on intestinal tissue fusion. Materials and methods: Radio-frequency-induced fusion was performed on ex vivo small intestine tissue. The effect on the fusion was observed by changing the control parameters (power, interval time, and terminal impedance) in the algorithm. The quality of fusion was evaluated using the burst pressure and thermal damage measurement. Histological evaluation was used to assess the fusion quality indirectly. Results: A maximum burst pressure of 8.460 ± 0.2674 KPa was acquired when the power was set to 100 W, the interval time was set to 2000 ms, and the terminal impedance was set to 50 Ω. Moreover, the thermal damage range increased with an increase in power but decreased with an increase in the interval time and terminal impedance. Furthermore, the thermal damage range and temperature were presumably related. Conclusions: For an ex vivo small intestine tissue, the appropriate control parameters could be set when the power was approximately 100 W, the interval time was approximately 2000 ms, and the terminal impedance was approximately 50 Ω. This study could provide a basis for the selection of control parameters for intestinal tissue fusion.

Metabolism is often regulated by the transcription and translation of RNA. In turn, it is likely that some metabolites regulate enzymes controlling reversible RNA modification, such as N

Precompression is vital when performing gastrointestinal anastomosis with staplers. However, research on the internal changes in intestinal tissue under stapling is lacking, and the effects of precompression have not been clarified. In this study, a stapler was modified, and the multifrequency bioimpedance of porcine small intestinal tissue was measured from before clamping the tissue with the stapler until the release of the tissue after precompression without firing. The Cole Y model was fitted to the bioimpedance, and the changes in the tissue were analyzed using the model parameters: G0, extracellular fluid conductance, and Δ G, intracellular fluid conductance. The results show that the changes of G0 and Δ G could be divided into four stages: rapid decrease, slow decrease, intense resilience, and slow recovery. During slow decrease stage, there was a greater decrease of G0 and Δ G (1.02E−05 ± 1.12E−05 S and 1.73E−05 ± 2.12E−05 S in precompression time’s increase, 1.68E−05 ± 8.74E−06 S and 1.20E−05 ± 1.09E−05 S in precompression strength’s increase). On the contrary, during intense resilience stage, there was a less increase of G0 and Δ G (0.88E−05 ± 4.86E−05 S and 9.15E−05 ± 9.37E−05 S in precompression time’s increase, 2.72E−05 ± 3.53E−05 S and 1.02E−04 ± 8.54E−05 S in precompression strength’s increase). In conclusion, the effects of precompression factors on tissue have been preliminary revealed: the tissue under precompression becomes thinner and less resilient. To improve the precompression effects and reduce any excessive pressure exerted on the staples by tissue resilience, the precompression time and strength should be increased appropriately.

Compressed natural gas (CNG) has been widely used as an automotive fuel in china, which the service security of CNG storage well (CSW), the main storage equipment in Chinese filling station, is becoming more and more prominent. In order to analyze the stress of CSW and its influencing factors, the mechanical model of CSW + cement sheath + stratum (CCS) processed by both elastic mechanics and finite element method was studied in this work. Using the most common well of Φ177.8× 10.36mm as a calculation case to obtain the analytic solutions and numerical solutions of CCS. The results indicated that the analytic solutions and numerical solutions are very close with relative deviation less than 3%, which verified their reliability each other. The calculation case can prove that the stress of CSW reduced evidently due to the effect of well cementation, which equivalent to the value of circular and axial stress of CSW strengthens to 18% and 20%. And when increasing the elastic modulus of cement sheath, the stress of CSW decreased that the support and potentiation to CSW by cement sheath becomes stronger.

Biodegradable magnesium (Mg) alloy emerges as revolutionary biomaterial by meeting both engineering and medical requirements for implants. In this study, we report a Mg alloy Mg-2.5Nd-0.21Zn-0.44Zr (wt. %, denoted as JDBM) potential for vascular stent application due to its outstanding performance in corrosion behaviors and biocompatibility. The investigation of corrosion properties evaluated by immersion test and electrochemical measurement shows less susceptibility to pitting corrosion and lower corrosion rate of JDBM as compared with AZ31 alloy. The corrosion products of JDBM do not cause significant adverse effect on the cell viability and growth during in vitro cytotoxicity test of the Mg extract via human vascular endothelial cells (HUVECs). We also investigated macrophage response to the Mg extract and observed compromised foreign body reaction (FBR) determined by human peripheral blood derived macrophage fusion and inflammatory cytokine and chemokine secretion. At last, we performed in vivo degradation assessment via implantation of JDBM stent in an animal model, and confirmed long-term stability and structural integrity of the stent in blood vessel. Thus, the JDBM alloy with excellent biocompatibility and long-term stability and durability in vivo, represents a significant advance in the development of biodegradable implants.

In recent years, fiber reinforced thermoplastic pipe (FRTP) has been widely used in oil fields of China due to its excellent corrosion resistance and coiling performance. With the further expansion of application scope, some failure accidents have occurred. Based on the inspection of the wall thickness, chemical composition and physical properties of a failed FRTP in the western oilfield of China, the causes are systematically analyzed. The results show that the main cause of the sample fracture is the decrease of the strength of FRTP due to the oil and gas media constantly penetrate into the lining and reinforced layer during the long-term service. Moreover, it is found that the outer sheath is worn and penetrated to the reinforced layer which further reduces the bearing pressure performance of FRTP and finally causes the fracture failure.

Clarifying changes in gastrointestinal tissue compressed by surgical stapler is a crucial prerequisite for stapler design optimization. For this study, a stapler was modified, and multifrequency bioimpedance of a porcine small intestine tissue compressed by the stapler was measured. The Cole Y model was fitted to the bioimpedance, and changes in tissue were analyzed using model parameters: G 0, extracellular fluid conductance; ΔG, intracellular fluid conductance; C cpeF, equivalent capacitance of cell membrane. The changes could be divided into two stages: first, all parameters decreased sharply with slopes more than 15.70 ± 2.67, 4.25 ± 1.23 μS/s and 72.68 ± 6.99 pF/s respectively; and subsequently, with an increase in compression strength, G 0 decreased with slopes less than 2.54 ± 0.40 μS/s, ΔG decreased slightly with slope of 0.26 ± 0.04 μS/s after fluctuating mildly, and C cpeF remained nearly invariant after initially increasing with slope of −2.94 ± 0.64 pF/s. In conclusion, when the stapler is closed, a portion of tissue is squeezed out of the measurement space, causing all parameters’ sharp decrease. Subsequently, the stapler continues compressing the tissue, leading to extracellular fluid expulsion. The changes in intracellular fluid are related to the compression strength and may be explained by cell restoration. This study could provide a basis for stapler design optimization.

Quantitative assessment of mammographic asymmetry has been investigated for breast cancer risk prediction. A new asymmetry feature extraction method was proposed in this study to enhance the risk prediction accuracy of near-term breast cancer. Breast areas in each pair of bilateral mammographic images were divided into several pairs of matched local annular regions and the maximum local asymmetry features (MLAF) were extracted from these regions. Radial basis function network (RBFN) was used to merge these features for breast cancer risk prediction. The dataset included 560 negative subjects. The risk prediction performance was tested using a leave-one-case-out (LOCO) cross-validation method. Area under the receiver operating characteristic curve (AUC) was used as the risk prediction performance evaluation index. AUC = 0.898 ± 0.013 was obtained by using the MLAFs extracted from the annular regions, which was significantly higher than the AUC value of 0.505 ± 0.025 achieved by using global asymmetry features computed from the whole breast regions (p

Endoscopic closure is an essential procedure in gastrointestinal (GI) surgery, but currently it is difficult to close large defects endoscopically because of the lack of an appropriate device. Previously, we developed an endoscopic clipping device that has multifiring function and is equipped with an independent clamp. The goal of this study is to provide a new closure method with this device and 4S-modified Roeder (4SMR) slipknot. The feasibility of the closure method is examined by deploying two clips during one insertion onto the 4SMR slipknot to close a 5 cm full-thickness linear defect of an ex vivo porcine stomach from the center. Mechanical strengths of clip-knot closure and the slipknot as regards to tensioning forces are also evaluated. Specifically, the mechanical strength of the 4SMR slipknot is verified by mean peak forces to failure, while the knot is tensioning by 2.5, 5, 7.5, and 10 N force (n = 20 for each group), respectively. Experimental results indicate the clip-slipknot closure can withstand a distracting force of 6.3 ± 5.6 N. Tensioning force has a great influence on the mechanical strength of slipknot, with the mean peak force (tensioning force) being 7.1± 6.5, 16.3 ± 9.3, 18.9 ± 10.4, and 24.2 ± 12.0 N, respectively. The proposed closure method can be used for large defects. Tensioning force higher than 5 N is suitable to ensure a stronger 4SMR slipknot.

Transcatheter closure of ventricular septal defect (VSD) has become an alternative therapy to open-chest surgery because of simple procedure, less invasion, and high safety [1–2]. The most important occluder device of the therapy is double-disc structure which occludes the VSD, with the discs of the occluder clamp the margin of VSD while the waist of the occluder supports the VSD hole (Figure 1(a)). Commercially available occluders are woven by 72 nitinol wires (Figure1(b)) and then formed by heat treatment. However, the implantation of metal occluders in perimembranous part will result in a substantial risk of complete atrioventricular block (cAVB) averaging 3.5%, because of its close proximity to the conduction system, which passes at the posterior border of defects [3]. To improve the biocompatibility, Huang [4] developed biodegradable VSD occluders (Figure 1(c)) which woven by polydioxanone (PDO) wires and can be fully absorbed within 24 weeks after implantation.

The administration of neoadjuvant chemotherapy (NAC) preceding radical cystectomy benefits overall survival for patients with muscle-invasive bladder cancer (MIBC). However, the relationship between the genetic profiling of MIBC and NAC response remains unclear. Here, a mutation panel of six cancer-associated genes (TSC1, FGFR3, TERT, TP53, PIK3CA and ERBB2) and an immunohistochemistry (IHC) panel containing eight bladder cancer (BC) biomarkers (EGFR, RRM1, PD-L1, BRCA1, TUBB3, ERCC, ERCC1, aberrantly glycosylated integrin α3β1 (AG) and CK5/6) were developed. BC samples from patients who showed a pathologic response (n = 39) and non-response (n = 13) were applied to the panel analysis. ERBB2, FGFR3 and PIK3CA exclusively altered in the responders group (19/39, 48.7%), in which FGFR3 mutations were significantly enriched in patients with a response in the cohort (14/39, 35.9%; P = 0.01). Additionally, strong expression of ERCC1 was associated with a pathologic response (P = 0.01). However, positive lymph node metastasis (P 0.01) and lymph-vascular invasion (LVI) (P = 0.03) were correlated with a non-response. Overall, the data show that FGFR3 mutations and elevated expression of ERCC1 in MIBCs are potential predictive biomarkers of the response to NAC.

Accurately detecting and removing pectoral muscle areas depicting on mediolateral oblique (MLO) view mammograms are an important step to develop a computer-aided detection scheme to assess global mammographic density or tissue patterns. This study aims to develop and test a new fully automated, accurate and robust method for segmenting pectoral muscle in MLO mammograms. The new method includes the following steps. First, a small rectangular region in the top-left corner of the MLO mammogram which may contain pectoral muscle is captured and enhanced by the fractional differential method. Next, an improved iterative threshold method is applied to segment a rough binary boundary of the pectoral muscle in the small region. Then, a rough contour is fitted with the least squares method on the basis of points of the rough boundary. Last, the fitting contour is subjected to local active contour evolution to obtain the final pectoral muscle segmentation line. The method has been tested on 720 MLO mammograms. The segmentation results generated using the new scheme were evaluated by two expert mammographic radiologists using a 5-scale rating system. More than 65% were rated above scale 3. When assessing the segmentation results generated using Hough transform, morphologic thresholding methods and Unet-based model, less than 20%, 35% and 47% of segmentation results were rated above scale 3 by two radiologists, respectively. Quantitative data analysis results show that the Dice coefficient of 0.986 ± 0.005 is obtained. In addition, the mean rate of errors and Hausdorff distance between the contours detected by automated and manual segmentation are FP = 1.71 ± 3.82%, FN = 5.20 ± 3.94% and 2.75 ± 1.39 mm separately. The proposed method can be used to segment the pectoral muscle in MLO mammograms with higher accuracy and robustness.

Combined inhibition of BRAF and MEK1/2 (CIBM) improves therapeutic efficacy of BRAF-mutant melanoma. However, drug resistance to CIBM is inevitable and the drug resistance mechanisms still remain to be elucidated. Here, we show that BMK1 pathway contributes to the drug resistance to CIBM. Considering that ERK1/2 pathway regulates cellular processes by phosphorylating, we first performed a SILAC phosphoproteomic profiling of CIBM. Phosphorylation of 239 proteins was identified to be downregulated, while phosphorylation of 47 proteins was upregulated. Following siRNA screening of 47 upregulated proteins indicated that the knockdown of BMK1 showed the most significant ability to inhibit the proliferation of CIBM resistant cells. It was found that phosphorylation of BMK1 was enhanced in resistant cells, which suggested an association of BMK1 with drug resistance. Further study indicated that phospho-activation of BMK1 by MEK5D enhanced the resistance to CIBM. Conversely, inhibition of BMK1 by shRNAi or BMK1 inhibitor (XMD8-92) impaired not only the acquirement of resistance to CIBM, but also the proliferation of CIBM resistant cells. Further kinome-scale siRNA screening demonstrated that SRC\MEK5 cascade promotes the phospho-activation of BMK1 in response to CIBM. Our study not only provides a global phosphoproteomic view of CIBM in melanoma, but also demonstrates that inhibition of BMK1 has therapeutic potential for the treatment of melanoma.

We report a Mg alloy Mg-2.2Nd-0.1Zn-0.4Zr (wt.%, denoted as JDBM-2) showing great potential in clinical vascular stent application by integrating the advantages of traditional medical stainless steel and polymer. This alloy exhibits high yield strength and elongation of 276 ± 6 MPa and 34.3 ± 3.4% respectively. The JDBM-2 with a stable degradation surface results in a highly homogeneous degradation mechanism and long-term structural and mechanical durability. In vitro cytotoxicity test of the Mg extract via human vascular endothelial cells (HUVECs) indicates that the corrosion products are well tolerated by the tested cells and potentially negligible toxic effect on arterial vessel walls. This alloy also exhibits compromised foreign body response (FBR) determined by human peripheral blood derived macrophage adhesion, foreign body giant cell (FBGC) formation and inflammatory cytokine and chemokine secretion. Finally, vascular stents manufactured from the JDBM-2 were implanted into rabbits for long-term evaluation. The results confirm excellent tissue compatibility and up to 6-month structural and mechanical integrity of the stent in vivo. Thus, the JDBM-2 stent with up to 6-month structural and mechanical integrity and excellent tissue compatibility represents a major breakthrough in this field and a promising alternative to traditional medical stainless steel and polymer for the clinical application.

Endoscopic closure after endoscopic mucosal resection (EMR), endoscopic submucosal dissection (EMR) or endoscopic full-thickness resection (EFTR) is necessary to eliminate serious complications. Through-the-Scope clips are usually used in treating GI bleeding and perforation for their convenience and reliable outcome, but they are not ideal when the perforation size is larger than 2 cm since their opening width is limited. Several approaches are introduced to reinforce the performance of clips in regarding gathering edges of large defect by using endoloop and clips with double-channel endoscope [1]. Recently, an innovative endoscopic suturing technique using slipknot string and clips with single-channel endoscope has been reported, which resulted in shorter procedure time [2]. However, slipknot cannot maintain for a long time when exposing to distractions due to its poor holding strength. We have designed and fabricated an endoscopic clipping device and reported its initial ex-vivo results [3]. In this paper, a new suturing method is presented by using this device incorporated with a 4S-Modified Roeder (4SMR) knot, which enables such device to close large defect in a short time. Furthermore, the mechanical strength of 4SMR knot is also studied.

Late stent thrombosis (LST) following drug-eluting stent (DES) implantation in patients with coronary artery disease (CAD) is often associated with delayed vascular healing, resulting from vascular inflammation and hypersensitivity to durable polymers and drugs. Therefore, DES design, materials, and coatings have been technologically revolutionized. Herein, we designed a novel abluminal groove-filled biodegradable polymer sirolimus-eluting stent (AGF-BP-SES), with a sirolimus content of only about one-third of traditional DES. The mechanical performances of AGF-BP-SES during compression and expansion were investigated. The pharmacokinetic (PK) profile of sirolimus was studied in the swine model. The in vivo efficacy of AGF-BP-SES was compared with that of Xience PRIME® stent. The results showed that AGF-BP-SES exhibited mechanical properties similar to traditional DES, including the rebound ratio of radial contraction/direction, rebound ratio of axial contraction/direction, and inhomogeneity of compression/expansion. Despite utilizing a reduced dose of sirolimus, AGF-BP-SES delivered sirolimus to the coronary artery in a controlled and efficient manner. The stent maintained a safe and effective local drug concentration without local or systemic risks. In the swine model, histopathological indicators predicted safety and biocompatibility of AGF-BP-SES. In conclusion, AGF-BP-SES maintained similar mechanical properties as other stents while reducing the drug-loading capacity, and showed a favorable safety and efficacy profile of the targeted DES.

Combined inhibition of BRAF and MEK1/2 (CIBM) improves therapeutic efficacy of BRAF-mutant melanoma. However, drug resistance to CIBM is inevitable and the drug resistance mechanisms still remain to be elucidated. Here, we show that BMK1 pathway contributes to the drug resistance to CIBM. Considering that ERK1/2 pathway regulates cellular processes by phosphorylating, we first performed a SILAC phosphoproteomic profiling of CIBM. Phosphorylation of 239 proteins was identified to be downregulated, while phosphorylation of 47 proteins was upregulated. Following siRNA screening of 47 upregulated proteins indicated that the knockdown of BMK1 showed the most significant ability to inhibit the proliferation of CIBM resistant cells. It was found that phosphorylation of BMK1 was enhanced in resistant cells, which suggested an association of BMK1 with drug resistance. Further study indicated that phospho-activation of BMK1 by MEK5D enhanced the resistance to CIBM. Conversely, inhibition of BMK1 by shRNAi or BMK1 inhibitor (XMD8-92) impaired not only the acquirement of resistance to CIBM, but also the proliferation of CIBM resistant cells. Further kinome-scale siRNA screening demonstrated that SRC\MEK5 cascade promotes the phospho-activation of BMK1 in response to CIBM. Our study not only provides a global phosphoproteomic view of CIBM in melanoma, but also demonstrates that inhibition of BMK1 has therapeutic potential for the treatment of melanoma.

An accurate detection of the effective values of electric voltage and current from high frequency power generators is a precondition for the development of smart electrotomes. In this light, an energy detection system based on personal computer (PC) is developed hereby. It senses voltage and current in isolation from generators with transformers, and then the measured values are amplified, filtered, transformed into single-ended signals and converted to RMS. The detected signals are transformed into digital signals through Data Acquisition Card (DAQ) and the data are processed with quadratic fit in Labview. Finally, the controller completes constant power output. The experiment results indicate that the energy detection system can measure the output parameters precisely and the controller can achieve constant power control.

Considering the problems such as reposition limited, easily detached and singly fired of the existing clip products, we developed an endoscopic multiple-clip applier which can apply 4 clips fired successively at a time. Th instrument also equipped with an independent grasper which can be used to clamp target tissues. In order to explor its feasibility and effectiveness of endoluminal closure of gastric perforation, 22 pig stomachs were making a 1 cm full-thickness incision from outside and closed by multiple-clip applier (n = 12) in vitro. Outcome was measured by bursting pressure and compared with negative control (n = 5) and hand suture (n = 5). We set a threshold pressure value (10 mm Hg) for a secure closure. Except 2 cases of invalid data, the mean bursting pressures of negative control, multiple-clip applier, hand suture were (1.5 ± 0.3) mm Hg, (46.0 ± 7.1) mm Hg, and (72.5 ± 7.7) mm Hg, respectively. The results showed that bursting pressure of multiple-clip applier was significantly higher than that of negative control (P0.05) and threshold value. Multiple-clip applier can be served as an effective and safe device to perform the endoluminal closure of gastric perforation.