Simulation-guided development of advanced PID control algorithm for skin cooling in radiofrequency lipolysis.

BACKGROUND: The clinical outcomes of bipolar radiofrequency (RF) lipolysis, a prevalent non-invasive fat reduction procedure, hinge on the delicate balance between effective lipolysis and patient safety, with skin overheating and subsequent tissue damage as primary concerns. OBJECTIVE: This study aimed to investigate a novel bipolar radiofrequency lipolysis technique, safeguarding the skin through an innovative PID temperature control algorithm. METHODS: Utilizing COMSOL Multiphysics simulation software, a two-dimensional fat and skin tissue model was established, simulating various PID temperature control schemes. The crux of the simulation involved a comparative analysis of different PID temperatures at 45 °C, 50 °C, and 55 °C and constant power strategies, assessing their implications on skin temperature. Concurrently, a custom bipolar radiofrequency lipolysis device was developed, with ex vivo experiments conducted using porcine tissue for empirical validation. RESULTS: The findings indicated that with PID settings of Kp = 7, Ki = 2, and Kd = 0, and skin temperature control at 45 °C or 50 °C, the innovative PID-based epidermal temperature control strategy successfully maintained the epidermal temperature within a safe range. This maintenance was achieved without compromising the effectiveness of RF lipolysis, significantly reducing the risk of thermal damage to the skin layers. CONCLUSION: Our research confirms the substantial practical utility of this advanced PID-based bipolar RF lipolysis technique in clinical aesthetic procedures, enhancing patient safety during adipose tissue ablation therapies.

A novel discrete linkage-type electrode for radiofrequency-induced intestinal anastomosis.

INTRODUCTION: For decades, radiofrequency (RF)-induced tissue fusion has garnered great attention due to its potential to replace sutures and staples for anastomosis of tissue reconstruction. However, the complexities of achieving high bonding strength and reducing excessive thermal damage present substantial limitations of existing fusion devices. MATERIALS AND METHODS: This study proposed a discrete linkage-type electrode to carry out ex vivo RF-induced intestinal anastomosis experiments. The anastomotic strength was examined by burst pressure and shear strength test. The degree of thermal damage was monitored through an infrared thermal imager. And the anastomotic stoma fused by the electrode was further investigated through histopathological and ultrastructural observation. RESULTS: The burst pressure and shear strength of anastomotic tissue can reach 62.2 ± 3.08 mmHg and 8.73 ± 1.11N, respectively, when the pressure, power and duration are 995 kPa, 160 W and 13 s, and the thermal damage can be controlled within limits. Histopathological and ultrastructural observation indicate that an intact and fully fused stomas with collagenic crosslink can be formed. CONCLUSION: The discrete linkage-type electrode presents favorable efficiency and security in RF-induced tissue fusion, and these results are informative to the design of electrosurgical medical devices with controllable pressure and energy delivery.

Design and implementation of mechanical property testing equipment for thoracic aortic stent grafts.

The mechanical properties of the stent graft are important factors influencing the outcome of TEVAR treatment and the occurrence of postoperative complications. The aim of this study is to improve and design a mechanical performance testing equipment for thoracic aortic stent grafts. The mechanical performance testing equipment consists of a radial force testing equipment of the stent graft designed by the wire compression grip method and a dynamic straightening force testing device with stable and controllable test conditions and continuously variable test angles. By constructing the testing equipment to physically measure the stent specimen, the experimental results reflect the trend of change and the simulation results are basically consistent, i.e. the mechanical properties of the thoracic aortic stent designed in this study is feasible and the measured data are valid. The testing equipment can provide the basis and reference direction for the quality testing of stent graft products, optimisation of mechanical properties of stent grafts and R&D innovation.

A novel electrode for reducing tissue thermal damage in radiofrequency-induced intestinal anastomosis.

PURPOSE: This study aimed to design a novel electrode for reducing tissue thermal damage in radiofrequency-induced intestinal anastomosis. MATERIAL AND METHODS: We developed and compared two electrodes (Ring electrode, and Plum electrode with reduced section of the middle fusion area by nearly 80% arising from novel structural design) by performing ex-vivo experiments and finite element analysis. RESULTS: In contrast to the Ring electrode group, slightly higher mean strength is acquired with the tensile force and burst pressure results increasing from 9.7 ± 1.47 N, 84.0 ± 5.99 mmHg to 11.1 ± 1.71 N, 89.4 ± 6.60 mmHg, respectively, as well as a significant reduction in tissue thermal damage for the Plum electrode group, with compression pressure of 20 kPa, RF energy of 120 W and welding duration of 8 s applied to the target regions to achieve anastomosis. Besides, the novel structural design of the Plum electrode can counteract the tension generated by intestinal peristalsis and enhance the biomechanical strength of the anastomotic area. The histological observation showed that the fusion area of the two-layer intestinal tissue is tightly connected with decreased thickness. CONCLUSION: The novel electrode (Plum electrode) could reduce tissue thermal damage in radiofrequency-induced intestinal anastomosis.

Biomechanical effects of osteoporosis severity on the occurrence of proximal junctional kyphosis following long-segment posterior thoracolumbar fusion.

BACKGROUND: Proximal junctional kyphosis is a common long-term complication in adult spinal deformity surgery that involves long-segment posterior spinal fusion. However, the underlying biomechanical mechanisms of the impact of osteoporosis on proximal junctional kyphosis remain unclear. The present study was to evaluate adjacent segment degeneration and spine mechanical instability in osteoporotic patients who underwent long-segment posterior thoracolumbar fusion. METHODS: Finite element models of the thoracolumbar spine T1-L5 with posterior long-segment T8-L5 fusion under different degrees of osteoporosis were constructed to analyze intervertebral disc stress characterization, vertebrae mechanical transfer, and pedicle screw system loads during various motions. FINDINGS: Compared with normal bone mass, the maximum von Mises stresses of T7 and T8 were increased by 20.32%, 22.38%, 44.69%, 4.49% and 29.48%, 17.84%, 40.95%, 3.20% during flexion, extension, lateral bending, and axial rotation in the mild osteoporosis model, and by 21.21%, 18.32%, 88.28%, 2.94% and 37.76%, 15.09%, 61.47%, -0.04% in severe osteoporosis model. The peak stresses among T6/T7, T7/T8, and T8/T9 discs were 14.77 MPa, 11.55 MPa, and 2.39 MPa under lateral bending conditions for the severe osteoporosis model, respectively. As the severity of osteoporosis increased, stress levels on SCR8 and SCR9 intensified during various movements. INTERPRETATION: Osteoporosis had an adverse effect on proximal junctional kyphosis. The stress levels in cortical bone, intervertebral discs and screws were increased with bone mass loss, which can easily lead to intervertebral disc degeneration, bone destruction as well as screw pullout. These factors have significantly affected or accelerated the occurrence of proximal junctional kyphosis.

Preliminary studies on intimal injury related to stent retrieval in a canine model.

OBJECTIVE: This pilot study aimed to observe intimal injuries related to stent retrieval in the iliac artery of a canine. BACKGROUND: In-stent restenosis remains challenging owing to permanent stent implantation. A retrievable stent may be alternative for intervention without permanent residue. METHODS: Five retrievable stents with point-to-point overlapped double-layer scaffolds were deployed into the iliac arteries and retrieved on days 14, 21, 28, 35, and 42 from five canines. RESULTS: Arterial diameter decreased by 9-10% before retrieval and 15% on day 14 after retrieval. In the 14-day-stent, the stent surface was clean without visible fibrin. In the 28-day-stent, the overlay was mainly composed of fibrin and fibroblasts. The proliferation of smooth muscle cells has not yet been observed with α-smooth muscle actin staining. In the 42-day-stent, endothelial and smooth muscle cells decreased under the struts, and the internal elastic lamina was interrupted segmentally. Neointima formation involves fibroblasts and smooth muscle cells. Neointimal thickness was negatively correlated with strut space. Stent traces on the artery wall tended to be flat at a follow-up14 days after retrieval. The primary intima was completely covered by neointima. Two stents could not be retrieved because of in-stent thrombosis or capture loss. CONCLUSIONS: The stent was covered mainly by depositional fibrin after 28 days and by typical neointima after 42 days. The stent retrieval procedure did not induce injury to vascular smooth muscle, and the intima repair was performed 14 days after stent retrieval.

[Segmentation of prostate region in magnetic resonance images based on improved V-Net].

Magnetic resonance (MR) imaging is an important tool for prostate cancer diagnosis, and accurate segmentation of MR prostate regions by computer-aided diagnostic techniques is important for the diagnosis of prostate cancer. In this paper, we propose an improved end-to-end three-dimensional image segmentation network using a deep learning approach to the traditional V-Net network (V-Net) network in order to provide more accurate image segmentation results. Firstly, we fused the soft attention mechanism into the traditional V-Net's jump connection, and combined short jump connection and small convolutional kernel to further improve the network segmentation accuracy. Then the prostate region was segmented using the Prostate MR Image Segmentation 2012 (PROMISE 12) challenge dataset, and the model was evaluated using the dice similarity coefficient (DSC) and Hausdorff distance (HD). The DSC and HD values of the segmented model could reach 0.903 and 3.912 mm, respectively. The experimental results show that the algorithm in this paper can provide more accurate three-dimensional segmentation results, which can accurately and efficiently segment prostate MR images and provide a reliable basis for clinical diagnosis and treatment.

Oleic Acid Dissolves cGAS-DNA Phase Separation to Inhibit Immune Surveillance.

Phase separation (PS) is a fundamental principle in diverse life processes including immunosurveillance. Despite numerous studies on PS, little is known about its dissolution. Here, it is shown that oleic acid (OA) dissolves the cyclic GMP-AMP synthase (cGAS)-deoxyribonucleic acid (DNA) PS and inhibits immune surveillance of DNA. As solvent components control PS and metabolites are abundant cellular components, it is speculated that some metabolite(s) may dissolve PS. Metabolite-screening reveals that the cGAS-DNA condensates formed via PS are markedly dissolved by long-chain fatty acids, including OA. OA revokes intracellular cGAS-PS and DNA-induced activation. OA attenuates cGAS-mediated antiviral and anticancer immunosurveillance. These results link metabolism and immunity by dissolving PS, which may be targeted for therapeutic interventions.

Spermine enhances antiviral and anticancer responses by stabilizing DNA binding with the DNA sensor cGAS.

Self-nonself discrimination is vital for the immune system to mount responses against pathogens while maintaining tolerance toward the host and innocuous commensals during homeostasis. Here, we investigated how indiscriminate DNA sensors, such as cyclic GMP-AMP synthase (cGAS), make this self-nonself distinction. Screening of a small-molecule library revealed that spermine, a well-known DNA condenser associated with viral DNA, markedly elevates cGAS activation. Mechanistically, spermine condenses DNA to enhance and stabilize cGAS-DNA binding, optimizing cGAS and downstream antiviral signaling. Spermine promotes condensation of viral, but not host nucleosome, DNA. Deletion of viral DNA-associated spermine, by propagating virus in spermine-deficient cells, reduced cGAS activation. Spermine depletion subsequently attenuated cGAS-mediated antiviral and anticancer immunity. Collectively, our results reveal a pathogenic DNA-associated molecular pattern that facilitates nonself recognition, linking metabolism and pathogen recognition.

Minimizing thermal damage using self-cooling jaws for radiofrequency intestinal tissue fusion.

INTRODUCTION: 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. MATERIAL AND METHODS: The prototype of self-cooling jaws was developed and manufactured. A total number of 60 mucosa-to-mucosa fusions were conducted using ex-vivo porcine intestinal segments with the proposed design and conventional bipolar jaws. The effects of intestinal fusion were evaluated based on temperature curves, burst pressure, thermal damage, and histological appearances. RESULTS: The 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. CONCLUSIONS: 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.

Whole exome analysis reveals the genomic profiling related to chemo-resistance in Chinese population with limited-disease small cell lung cancer.

PURPOSE: 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). EXPERIMENTAL DESIGN: 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. RESULTS: 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. CONCLUSION: 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.

DNA mechanical flexibility controls DNA potential to activate cGAS-mediated immune surveillance.

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.

Seed Vigour and Morphological and Physiological Characteristics of Epimedium brevicornu Maxim: In Different Stages of Seed Development.

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.

Application of an Optical Tracking System for Motor Skill Assessment in Laparoscopic Surgery.

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.

Motion Measurement and Analysis of Different Instruments for Single-Incision Laparoscopic Surgery.

Objective: To objectively compare and analyze the range of motion of three types of instruments for single-incision laparoscopic surgery. Material and Methods. Ten experienced participants were recruited. Straight instruments (Group A), straight/articulating instruments (Group B), and precurved instruments (Group C) were used to complete the transferring task through one site in a laparoscopic simulator. Straight instruments via two separate sites (Group D) served as control. The operation time of each group was recorded. Instrument positions were measured by an optical tracking system. The inserted length and pivoting angles were derived via MATLAB. Results: There was a significant difference in operation time between groups (D < A < B < C, p < 0.01). The range of motion of instruments was different on instrument types and surgical approaches. A significant difference in the inserted length was found between groups. Instrument conflicts and inadequate triangulation were found in Group A; instrument conflicts were found in Group B; no obvious conflicts and triangulation problems were observed in Group C. The operation in Group C was similar to the operation in Group D but differed on the left/right pivoting angles. Conclusion: Different types of instruments have different ranges of motion in single-incision laparoscopic surgery. Working with precurved instruments seems like a compromise to traditional laparoscopic surgery if the transmission property, and shaft curvature of the instruments could be improved. An integrated mechanical platform or robotic system might be the ultimate solution for single-incision laparoscopic surgery to pursue even less trauma.

A Study on the Static Magnetic and Electromagnetic Properties of Silica-Coated Carbonyl Iron Powder after Heat Treatment for Improving Thermal Stability.

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.

Identification and Classification of Parkinsonian and Essential Tremors for Diagnosis Using Machine Learning Algorithms.

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.

Whole-genome sequencing reveals the evolutionary trajectory of HBV-related hepatocellular carcinoma early recurrence.

Patients with hepatocellular carcinoma (HCC) have poor long-term survival following curative resection because of the high rate of tumor early recurrence. Little is known about the trajectory of genomic evolution from primary to early-recurrent HCC. In this study, we performed whole-genome sequencing (WGS) on 40 pairs of primary and early-recurrent hepatitis B virus (HBV)-related HCC tumors from patients who received curative resection, and from four patients whose primary and recurrent tumor were extensively sampled. We identified two recurrence patterns: de novo recurrence (18/40), which developed genetically independently of the primary tumor and carried different HCC drivers, and ancestral recurrence (22/40), which was clonally related to the primary tumor and progressed more rapidly than de novo recurrence. We found that the recurrence location was predictive of the recurrence pattern: distant recurrence tended to display the de novo pattern, whereas local recurrence tended to display the ancestral pattern. We then uncovered the evolutionary trajectories based on the subclonal architecture, driver-gene mutations, and mutational processes observed in the primary and recurrent tumors. Multi-region WGS demonstrated spatiotemporal heterogeneity and polyclonal, monophyletic dissemination in HCC ancestral recurrence. In addition, we identified recurrence-specific mutations and copy-number gains in BCL9, leading to WNT/ß-catenin signaling activation and an immune-excluded tumor microenvironment, which suggests that BCL9 might serve as a new therapeutic target for recurrent HCC. Collectively, our results allow us to view with unprecedented clarity the genomic evolution during HBV-related HCC early recurrence, providing an important molecular foundation for enhanced understanding of HCC with implications for personalized therapy to improve patient survival.