Numerical analysis and animal study of noninvasive handheld electroporation delivery device for skin superficial lesion treatment.

INTRODUCTION: This study aims to investigate the feasibility of a noninvasive handheld electroporation pulses delivery device (EPDD) for electroporation-based treatment (EBT) of skin superficial lesions through numerical analysis and animal study. METHODS: Finite element analysis was performed to investigate the performance of the EPDD. The electric field, temperature, EI and TI were calculated under pulse voltages of 600, 800, and 1000 V. A mouse subcutaneous tumor model was established to evaluate the performance of the EPDD through histopathology and survival analyses. RESULTS: The electrical field strength increased from 151 (600 V) to 252 V/cm (1000 V) in the skin and from 1302 (600 V) to 2171 V/cm (1000 V) in the tumor. The volume of EI grew and reached a plateau at the 165th pulse, whereas the maximum volume of EI increased with higher voltage. The growth tendency of TI differed between groups, and it was higher in the high-voltage group (HVG) than in the low-voltage group. Histopathological analysis showed that the depth and range of the ablation area could be controlled by adjusting pulse voltage. Survival analysis showed that the survival of the HVG was better than that of the low-voltage and the control group (p < 0.01). CONCLUSIONS: The results demonstrate that the EPDD is feasible, safe, and effective for skin EBT. The volume of EP tissue injury can be controlled by adjusting the pulse voltage, pulse number, and other parameters. The proposed noninvasive handheld EPDD can be a potential therapeutic tool for EBT of superficial skin lesions in the future.

Preoperative platelet count predicts posttransplant portal vein complications in orthotopic liver transplantation: a propensity score analysis.

BACKGROUND: The role of platelets on the prognosis of patients with liver transplantation remains unclear. Thus, we aimed to evaluate the influence of preoperative platelet count on postoperative morbidity after liver transplantation. METHODS: Clinical data of the patients who received liver transplantation from January 2015 to September 2018 were evaluated. RESULTS: Of the 329 patients included, the average age was 46.71 ± 0.55 years, and 243 were men (75.2%). The incidence of posttransplant portal vein complication was significantly higher in the high platelet count group (> 49.5 × 109/L; n = 167) than in the low platelet count group (≤ 49.5 × 109/L, n = 162, 12.6% vs. 1.9%). After multivariable regression analysis, high platelet count was independently associated with postoperative portal vein complication (odds ratio [OR]: 8.821, 95% confidence interval [CI]: 2.260 to 34.437). After the inverse probability of treatment weighting analysis, patients in the high platelet count group had significantly higher risk of portal vein complication (OR: 9.210, 95%CI: 1.907 to 44.498, p = 0.006) and early allograft dysfunction (OR: 2.087, 95%CI: 1.131 to 3.853, p = 0.019). CONCLUSIONS: Preoperative platelet count > 49.5 × 109/L was an independent risk factor for posttransplant portal vein complication and early allograft dysfunction. High preoperative platelet count could be an adverse prognostic predictor for liver transplantation recipients.

Physiological and histopathological effects of electroporation pulse on stomach of rats.

BACKGROUND: Irreversible electroporation (IRE) is an emerging tissue ablation technique with widespread potential, especially for cancer treatment. Although the safety and efficacy of IRE for gastric tissue ablation have been demonstrated, there is a gap of knowledge regarding the effect of electroporation pulse (EP) on the physiology and histopathology of the stomach. This study applied EP to the stomach of healthy rats and investigated the digestive function, serum marker levels, and gastric tissue structure of EP-treated rats. METHODS: Ninety male rats were divided into nine groups and examined up to 28 days post-treatment. A single burst of electroporation pulse (500 V, 99 pluses, 1 Hz, 100 µs) was delivered to the stomachs of rats using a tweezer-style round electrode. Gastric emptying, small intestinal transit, and gastric secretion were measured to evaluate the digestive function. Serum marker levels were determined using ELISA. Haematoxylin-eosin, Masson trichrome, and immunofluorescence were performed for histopathological analysis. RESULTS: No  significant effect on gastric emptying or secretion was found post-EP, whereas the small intestinal transit decreased at 4 h and rapidly recovered to normal on 1-day post-EP. Further, serum TNF-α and IL-1ß levels temporarily changed during the acute phase but returned to baseline within 28 days. Moreover, histopathological analysis revealed that cell death occurred immediately post-EP in the ablation area, whereas the gastric wall scaffold in the ablation region remained intact post-EP. CONCLUSIONS: This study demonstrates the safety and efficacy of EP on the physiology and histopathology of the stomach and lays a foundation for more comprehensive applications of this technique.

Magnetic anchoring and guidance-assisted endoscopic irreversible electroporation for gastric mucosal ablation: a preclinical study in canine model.

BACKGROUND: The aim of this study was to evaluate the feasibility, safety, and efficacy of magnetic anchoring and guidance-assisted endoscopic irreversible electroporation (MAG-IRE) for gastric mucosal ablation. METHODS: A catheter-based, donut-like, and MAG-assisted electrode was developed. MAG-IRE for gastric mucosal ablation was performed in eight beagle canines. The parameters of one set of IRE was 500 V voltage, 100 µs pulse duration, and 99 pulses. The MAG time, operation time, success rate, and adverse events were measured. Endoscopic examination was performed from 30 min to 28 days post-IRE. Full-thickness gastric tissue was harvested by wedge biopsy for histopathological analysis. RESULTS: 30 (93.75%) of the 32 lesions were successfully ablated by MAG-IRE. The median MAG time was 300 s (IQR 120-422.5 s), and the median operation time was 491.5 s (IQR 358.3-632.5 s). No adverse events occurred. Ulceration was observed, starting from 3 days post-IRE. The mucosa healed 14 to 28 days post-IRE. Hematoxylin-Eosin (H&E) staining showed inflammatory infiltration, edema, and congestion in the ablated mucosa. Masson's Trichrome staining showed that the gastric wall and blood vessels in the ablation area were intact. TUNEL assay showed diffuse positive cells in ablated mucosa as early as 30 min post-IRE. CONCLUSIONS: MAG-IRE for gastric mucosal ablation is feasible, safe, and effective. It can be a potential therapeutic option for minimally invasive treatment of gastric neoplasm.

Safety and efficacy of magnetic anchoring electrode-assisted irreversible electroporation for gastric tissue ablation.

BACKGROUND: Irreversible electroporation (IRE) is an emerging tissue ablation technique, which is safe for sites where thermal-basis techniques are not suitable. The aim of this study is to evaluate the safety and efficacy of magnetic anchoring electrode (MAE)-assisted IRE for normal gastric tissue ablation in a rabbit model. METHODS: IRE (500 V, 100 µs, 99 pulses, 1 Hz) of the gastric wall was performed in 24 adult New Zealand rabbits with a novel catheter-mounted MAE with fluoroscopy and a surgical approach. Procedure time, procedure-related bleeding, perforation, and other complications were recorded. Animals were sacrificed at 30 min, 1 day, 3 days, 7 days, 14 days, and 28 days post-IRE. The stomach was removed en bloc, and the diameter of each lesion was measured. Histopathological analyses by Hematoxylin-Eosin (H&E), masson trichrome, alpha-smooth muscle action (α-SMA), and terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) were performed. RESULTS: Gastric tissue ablation with MAE-assisted IRE was successfully performed without any interruption. No perforation or bleeding was observed during IRE or throughout the follow-up period. A demarcated hemorrhage was found in the ablated area upon gross examination. H&E staining showed complete cell death with inflammatory infiltration, edema, and hemorrhaging. TUNEL presented diffuse positive cells in the ablated area. The tissue scaffold was well preserved without damage as indicated by Masson trichrome staining. Ulceration was observed starting from 3 days post-IRE. The mucosal layer was gradually recovered and regenerated within 14-28 days. No other complication was observed post-IRE. CONCLUSIONS: MAE-assisted IRE is safe and effective for normal gastric tissue ablation and the gastric wall recovered in 14-28 days post-IRE.

[Research Progress of Catheter-based Irreversible Electroporation for Tissue Ablation].

Irreversible electroporation (IRE) is an emerging tissue ablation technique. Compared with thermal ablation technique such as radiofrequency, IRE can achieve focal ablation in a shorter time without heat sink effect while sparing the tissue scaffold. IRE has been demonstrated to be a feasible therapeutic modality for the liver, pancreatic, and prostatic cancer. In recent years, several studies regarding of catheter-directed IRE for digestive tract, bronchus, urinary tract, and myocardium have been performed, which preliminarily demonstrated the safety and efficacy of IRE for tissue ablation under endoscopic or interventional technique. This study summarized the research progress of catheter-directed IRE for tissue ablation. The critical technique and future direction of catheter-based IRE are prosp.

Electrical and thermal analyses of catheter-based irreversible electroporation of digestive tract.

Introduction: Irreversible electroporation (IRE) combined with a catheter-based electrode during endoscopy is a potential alternative treatment method for digestive tract tumors. The aim of this study was to investigate the electrical injury (EI) and thermal injury (TI) to the digestive tract via numerical analyses and to evaluate the role and impact of electrode configurations and pulse settings on the efficacy and outcomes of IRE. Materials and methods: A finite element method was used to solve the numerical model. A digestive tract model having 4-mm-thick walls and two catheter-based electrode configuration models were constructed. The distributions of electric fields, temperature, electrical conductivity, tissue injury and limitation on the pulse number required for IRE were calculated and compared. Results: Electrode length is an important geometric parameter for electrodes in the monopolar model (MPM), while electrode spacing affects the outcomes in the bipolar model (BPM). Increasing the pulse voltage reduces the pulse number required for tissue ablation, while increasing the risk of TI. In total, there were 6 NT-IRE protocols, 12 thermal-IRE protocols and 30 TI protocols. All of the NT-IRE protocols were set in BPMs with a voltage of 0.50 kV. With increasing electrode spacing, the minimum pulse number decreased. However, thermal effects were inevitable in the MPM. Conclusions: The electrode configuration and pulse settings are adjusted to achieve NT-IRE synergistically. The BPM is more reliable for achieving NT-IRE in 4-mm-thick digestive wall. Future in vitro and in vivo studies are needed to support and validate this conclusion.

A Novel Remote-Controlled Injection Device for T-Tube Cholangiography: A Feasibility Study in Canines.

BACKGROUND The purpose of this study was to develop a remote-controlled injection device for T-tube cholangiography to avoid occupational exposure. MATERIAL AND METHODS The remote-controlled injection device has 3 major components: an injection pump, a pressure sensor, and a wireless remote-control panel. The feasibility and effectiveness of this device for T-tube cholangiography was evaluated in ex vivo porcine livers using a laparoscopic training platform and in in vivo canine experiments. RESULTS The contrast dye was successfully injected into the biliary tracts of the ex vivo porcine liver and canines by the designed device. The X-ray images clearly showed the anatomical structure of the bile ducts. No obvious adverse reaction was observed in the dogs during or after the procedure. All steps were controlled remotely, avoiding ionizing radiation exposure to the surgeons. CONCLUSIONS This novel remote-controlled injection device for T-tube cholangiography can assist operators in completing cholangiography remotely and protecting them from occupational exposure.

Prognostic Factors and Treatment Options for Patients with High-Grade Chondrosarcoma.

BACKGROUND The goal of this study was to determine the prognostic factors exclusive for high-grade chondrosarcoma and whether adjuvant radiotherapy could achieve better overall survival (OS) or cancer-specific survival (CSS) for patients with high-grade chondrosarcoma. MATERIAL AND METHODS Surveillance, Epidemiology, and End Results (SEER) cancer registry database was utilized to extract the chondrosarcoma cases diagnosed between 1973 and 2014. Among these cases, the histological grades of poorly differentiated (grade 3) and undifferentiated (grade 4) were categorized as high-grade and included in this study. Chondrosarcoma OS and CSS were the primary outcomes in the present study. The log-rank test was performed for univariate analysis, and the Cox regression model was conducted for multivariate analysis. RESULTS A total of 743 patients with high-grade chondrosarcoma were identified in this study (430 cases were poorly differentiated tumors, and 313 cases were undifferentiated tumors). Age at diagnosis, pathological grade, histo-type, SEER stage, tumor size and surgical resection were identified as independent predictors in both OS and CSS analysis of high-grade chondrosarcoma. When stratified by histological grade, surgical resection remained the effective treatment. Strikingly, radiotherapy was determined as an independent protective factor in both OS and CSS analysis of undifferentiated (grade 4) dedifferentiated chondrosarcoma, and adjuvant radiotherapy combined surgical resection could improve both the OS and CSS of patients with undifferentiated myxoid and dedifferentiated chondrosarcoma compared with other treatment regimens. CONCLUSIONS Our study first demonstrated that adjuvant radiotherapy combined surgery could improve the survival of patients with undifferentiated myxoid and dedifferentiated chondrosarcoma. These results encourage the application of adjuvant radiotherapy for patients with high-grade chondrosarcoma and maximize the patients' outcome.

Marital Status and Survival of Patients with Chondrosarcoma: A Population-Based Analysis.

BACKGROUND Previous studies have shown that differences in marital status contribute to different prognoses for certain cancers, but the relationship between marital status and the prognosis of chondrosarcoma has not been reported previously. MATERIAL AND METHODS In this study, we selected 4502 eligible cases through the Surveillance, Epidemiology, and End Results (SEER) database from 1977 to 2014 to analyze the impact of marital status on chondrosarcoma cancer-specific survival (CSS) by Kaplan-Meier method and Cox regression model. RESULTS The sex, age, histotype, pathological grade, tumor location, tumor size, SEER stage, socioeconomic status, marital status, and treatment were identified as independent prognostic factors for chondrosarcoma CSS. Widowed patients presented the worst CSS compared with their married, divorced, and single counterparts (P<0.001). Subgroup analyses showed widowed patients also had a significantly higher risk of cancer-specific mortality compared with married patients in localized stage (HR: 1.971, 95% CI: 1.298-2.994, P=0.001), regional stage (HR: 1.535, 95% CI: 1.094-2.154, P=0.013), low pathological grade (HR: 1.866, 95% CI: 1.332-2.613, P<0.001), and high pathological grade (HR: 1.662, 95% CI: 1.139-2.426, P=0.008). CONCLUSIONS Marital status was first identified as an independent prognostic factor for chondrosarcoma CSS, and widowhood was always associated with a high risk of cancer-specific mortality. It is necessary to provide timely psychological treatment for widowed patients in clinical practice, which can improve the survival of chondrosarcoma patients.

[Development of Biliary Contrast Agents Remote Pushing Device].

A biliary contrast agents pushing device, including a syringe pushing system and a remote controller is introduced. The syringe pushing system comprises an injector card slot, a support platform and an injection bolus fader. A 20 mL syringe can be fitted on the syringe pushing system and kept with the ground about 30 degree. This system can perform air bubble pumping back and contrast agents bolus injection as well as speed adjustment. Remote controller is an infrared remote control which can start and stop the syringe pushing system. With this device, the remote controlled cholangiography technology can be achieved, which can not only protect doctors from X-ray radiation but also improve the traditional T-tube cholangiography and the contrast effect, reduce postoperative complications in patients as well. The application of this device will improve the current diagnosis and treatment system, the device will benefit the majority of doctors and patients.

[The Development of the Supermicroinvasive Magnetic Anchoring Laparoscopic System].

A magnetic anchoring supermicroinvasive laparoscopic system, including in vitro magnetic navigation handle and in vivo magnetic anchor laparoscopy is introduced. The magnetic anchor laparoscopic comprises an outer cannula, two data lines, a camera, a high color temperature LED light and two inner magnets. It is tiny enough to enter the abdominal cavity through conventional laparoscopic trocar and achieve orientation, navigation as wel as adjustment thefi eld of view within the abdominal cavity by attracting with the in vitro magnetic handle, thus it does not take up space of the laparoscopic trocar in working state. The system which can not only apply in single-port laparoscopic surgery based on a single traditional laparoscopic trocar but also apply in traditional laparoscopic surgery with less trocar, wil enhance the extent of minimaly invasive surgery and reduce the operation diffi culty at the same time. The clinical application of the system wil optimize the minimaly invasive techniques and benefi t the patients.

[A Canine Portal Hypertension Model Induced by Intra-portal Administration of Polyurethane-Tetrahydrofuran Solutions].

This study was to build a canine portal hypertension model by intra-portal administration of high polymer material polyurethane and organic solvent tetrahydrofuran mixed solutions in order to evaluate the effectiveness of the model. Twelve local crossbreed dogs were selected randomly, with intra-portal administration of 8% (weight/volume) polyurethane- tetrahydrofuran solutions through an incision in the upper abdomen to build the portal hypertension model. We measured the portal vein pressure before modeling, during modeling, and four-, eight-, and twelve- weeks after modeling, respectively. Then we evaluated the effectiveness of the model comparing values of data with those data obtained before modeling started, which were regarded as the normal values. The results showed that the portal vein pressure rose by 2. 5 times after the solution administrated instantly as much as that before modeling, and maintained at 1. 5 times after 4 weeks. This method presents an easy operation, low animal mortality and reliable model of portal hypertension. Its less abdominal adhesions and its ability in keeping normal anatomic structure specially make it suit for surgical research of portal hypertension.

[The Current Status and Prospects of Single-Port Laparoscopic Flexible Instrument in Surgery].

In recent years, the emergence of single-port laparoscopic technology promoted the development of the technology of laparoscopy, but deficiencies like equipment conflict or lack of triangulation severely hampered the clinical application of this technology. The appearance of single-port laparoscopic flexible instruments makes up for those deficiencies to a great extent. The element is to add a wrist joint to the tip of the instrument to form triangulation and reduce equipment conflict. But this technique is still in an early stage of development. The purpose of this article is to summarize the characteristics and problems of existing flexible single-port laparoscopic instruments, and to provide information for the further improvement, finally the future development was expected.

[The Application of Machine Perfusion on Clinical Liver Transplantation].

Liver transplantation is the only way to treat end-stage liver disease. In order to overcome the shortage of donor, marginal donors have been used widely, which bring about a series of problems. Machine perfusion can stimulate the circulation in vivo and is beneficial for the protection of liver. It could also improve the graft function and reduce postoperative complications, which makes it a hot spot in recent years. The aim of this study is to summarize the current status and prospects of application of machine perfusion on clinical liver transplantation.

Advantages of pulsed electric field ablation for COPD: Excellent killing effect on goblet cells.

Mucus hypersecretion resulting from excessive proliferation and metaplasia of goblet cells in the airways is the pathological foundation for Chronic obstructive pulmonary disease (COPD). Clinical trials have confirmed the clinical efficacy of pulsed electric field ablation (PFA) for COPD, but its underlying mechanisms is poorly understood. Cellular and animal models of COPD (rich in goblet cells) were established in this study to detect goblet cells' sensitivity to PFA. Schwan's equation was adopted to calculate the cells' transmembrane potential and the electroporation areas in the cell membrane. We found that goblet cells are more sensitive to low-intensity PFA (250 V/cm-500 V/cm) than BEAS-2B cells. It is attributed to the larger size of goblet cells, which allows a stronger transmembrane potential formation under the same electric field strength. Additionally, the transmembrane potential of larger-sized cells can reach the cell membrane electroporation threshold in more areas. Trypan blue staining confirmed that the cells underwent IRE rate was higher in goblet cells than in BEAS-2B cells. Animal experiments also confirmed that the airway epithelium of COPD is more sensitive to PFA. We conclude that lower-intensity PFA can selectively kill goblet cells in the COPD airway epithelium, ultimately achieving the therapeutic effect of treating COPD.

Memristor-Based Neuromorphic Chips.

In the era of information, characterized by an exponential growth in data volume and an escalating level of data abstraction, there has been a substantial focus on brain-like chips, which are known for their robust processing power and energy-efficient operation. Memristors are widely acknowledged as the optimal electronic devices for the realization of neuromorphic computing, due to their innate ability to emulate the interconnection and information transfer processes witnessed among neurons. This review paper focuses on memristor-based neuromorphic chips, which provide an extensive description of the working principle and characteristic features of memristors, along with their applications in the realm of neuromorphic chips. Subsequently, a thorough discussion of the memristor array, which serves as the pivotal component of the neuromorphic chip, as well as an examination of the present mainstream neural networks, is delved. Furthermore, the design of the neuromorphic chip is categorized into three crucial sections, including synapse-neuron cores, networks on chip (NoC), and neural network design. Finally, the key performance metrics of the chip is highlighted, as well as the key metrics related to the memristor devices are employed to realize both the synaptic and neuronal components.

A reversible implantable memristor for health monitoring applications.

Conventional implantable electronics based on von Neumann architectures encounter significant limitations in computing and processing vast biological information due to computational bottlenecks. The memristor with integrated memory-computing and low power consumption offer a promising solution to overcome the computational bottleneck and Moore's law limitations of traditional silicon-based implantable devices, making them the most promising candidates for next-generation implantable devices. In this work, a highly stable memristor with an Ag/BaTiO3/MnO2/FTO structure was fabricated, demonstrating retention characteristics exceeding 1200 cycles and endurance above 1000 s. The device successfully exhibited three-stage responses to biological signals after implantation in SD (Sprague-Dawley) rats. Importantly, the memristor perform remarkable reversibility, maintaining over 100 cycles of stable repetition even after extraction from the rat. This study provides a new perspective on the biomedical application of memristors, expanding the potential of implantable memristive devices in intelligent medical fields such as health monitoring and auxiliary diagnostics.

Survival model database of human digestive system cells exposed to electroporation pulses: An in vitro and in silico study.

Background and objectives: This study aimed to establish a mathematical survival model database containing cell-specific coefficients from human digestive system cells exposed to electroporation pulses (EPs). Materials and methods: A total of 20 types of human digestive system cell lines were selected to investigate the effect of EPs on cell viability. Cell viability was measured after exposure to various pulse settings, and a cell survival model was established using the Peleg-Fermi model. Next, the cell-specific coefficients of each cell line were determined. Results: Cell viability tended to decrease when exposed to stronger electric field strength (EFS), longer pulse duration, and more pulse number, but the decreasing tendency varied among different cell lines. When exposed to a lower EFS (<1,000 V/cm), only a slight decrease in cell viability occurred. All cell lines showed a similar tendency: the extent of electrical injury (EI) increased with the increase in pulse number and duration. However, there existed differences in heat sensitivity among organs. Conclusions: This database can be used for the application of electroporation-based treatment (EBT) in the digestive system to predict cell survival and tissue injury distribution during the treatment.

Injectable Self-Healing Adhesive pH-Responsive Hydrogels Accelerate Gastric Hemostasis and Wound Healing.

Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are well-established therapeutics for gastrointestinal neoplasias, but complications after EMR/ESD, including bleeding and perforation, result in additional treatment morbidity and even threaten the lives of patients. Thus, designing biomaterials to treat gastric bleeding and wound healing after endoscopic treatment is highly desired and remains a challenge. Herein, a series of injectable pH-responsive self-healing adhesive hydrogels based on acryloyl-6-aminocaproic acid (AA) and AA-g-N-hydroxysuccinimide (AA-NHS) were developed, and their great potential as endoscopic sprayable bioadhesive materials to efficiently stop hemorrhage and promote the wound healing process was further demonstrated in a swine gastric hemorrhage/wound model. The hydrogels showed a suitable gelation time, an autonomous and efficient self-healing capacity, hemostatic properties, and good biocompatibility. With the introduction of AA-NHS as a micro-cross-linker, the hydrogels exhibited enhanced adhesive strength. A swine gastric hemorrhage in vivo model demonstrated that the hydrogels showed good hemostatic performance by stopping acute arterial bleeding and preventing delayed bleeding. A gastric wound model indicated that the hydrogels showed excellent treatment effects with significantly enhanced wound healing with type I collagen deposition, α-SMA expression, and blood vessel formation. These injectable self-healing adhesive hydrogels exhibited great potential to treat gastric wounds after endoscopic treatment.