Coagulative Necrosis Research Articles

Safety and myocardio-necrosis laboratory data trend in patients undergoing atrial fibrillation catheter ablation: pulsed field ablation vs. radiofrequency ablation

Abstract Background Pulsed Field Ablation (PFA) is an innovative technology to perform atrial fibrillation (AF) catheter ablation. No form of thermal energy is used, but an irreversible electroporation mechanism that causes selective cardiomyocytes death, sparing the cells of adjacent tissues. There are few data in the literature about peri-procedural trend of myocardium-necrosis laboratory data in patients undergoing PFA versus those with radiofrequency (RF). Purpose Compare the short-term safety and the peri-procedural trend of myocardium-necrosis laboratory data in patients undergoing PFA with those undergoing standard-power (40W) RF catheter ablation. Methods 50 patients undergoing paroxysmal AF catheter ablation with pulmonary veins isolation were retrospectively enrolled, 25 treated with PFA and 25 with RF (matched for age, sex, BMI, left atrium size). The PFA protocol involved four two-second deliveries with the penta-spline catheter in the "basket" and in the "flower" configuration; about RF ablation, circular lesions were carried out at the antrum of each pulmonary vein. All patients underwent serial blood samples including troponin I (TnI, n.v. 0-50 ng/L) and CKMB (n.v 0-5 ng/mL) at time 0 and at 3, 24 and 48 post-procedure hours. Complication were evaluated at pre-discharge visit and at 3-month follow-up. Results The clinical and echocardiographic patient’s characteristics are summarized in Table 1. The TnI and CKMB baseline values were within normal range for all patients, both those treated with PFA and those treated with RF, and there were no statistically significant differences between the two group. Regarding the TnI and CKMB values temporal increase, a statistically significant increase was observed in patients treated with PFA (Table 2). The TnI percentage decrease over the 48 hours in RF-treated patients, although not statistically significant, is slower compared to patients treated with PFA. This data could be explained by considering that PFA causes acute damage (myocardiocytes necrosis by electroporation) with less inflammation and a less progressive nature, while RF causes damage with greater irritation and progression (coagulative necrosis) that may result in myocardial necrosis even in the subsequent hours. Despite evidence of greater myocardial necrosis, there were not procedural complications in those treated with PFA. Therefore, the TnI increase is indicative of selective myocardial damage, likely more antral. Conclusion The increase of myocardio-necrosis laboratory data appears to be higher using PFA compared to RF, and it is not associated with greater adverse events. The trend of the myocardio-necrosis laboratory data shows different reduction curves between PFA and RF, probably related to different ablation power source; these data will need to be re-analysed with a greater number of cases.Table 1Table 2

Technical principles of ablation therapy

Catheter ablation is astandard procedure in modern cardiology. It can significantly improve the quality of life and life expectancy of cardiac arrhythmia patients. Besides cardiac mapping, ablation itself is afundamental step tosuccessfully treat cardiac arrhythmias. There are various ablation technologies at hand: In traditional radiofrequency (RF) ablation, electrical current flow generates coagulation necrosis. When understanding the biophysical principles of RF ablation, the investigator is capable to adapt lesion geometry and size to the requirements of the procedure and vary them individually. In addition, lesion metric indices evaluate and integrate important parameters such as power, duration, impedance and contact force to standardize and control RF lesions. Cryoablation induces ice crystals within myocardial tissue, which lead to destruction and electrical scarring of the treated tissue. Histologically, cryolesions are well-delineated with preserved tissue architecture and intact endocardium. Pulsed field ablation (PFA) is anovel rising technology, particularly used for pulmonary vein isolation. In contrast to classic thermal technologies (RF and cryoablation), PFA uses pulsed electrical fields to electroporate cardiac tissue and thereby creates damage on acellular level only.

Multiparametric MRI manifestations of the spontaneous intratumoral coagulative necrosis in HCC.

To investigate the MRI manifestations of the spontaneous intratumoral coagulative necrosis (iCN) in patients with hepatocellular carcinoma (HCC) and its value in predicting the postoperative early recurrence (≤ 2years). Patients with HCC who underwent preoperative multiparametric MRI between January 2015 and February 2019 were enrolled in this retrospective study. The MRI manifestations of iCNs on TIWI, T2WI, and ADC were recorded. The sensitivity and specificity of MRI for the detection of iCNs were also evaluated. A multivariable Cox proportional hazards model and the Kaplan-Meier method were used to verify the value of histologically-confirmed and MRI-identified iCNs, respectively, in predicting early recurrence. A total of 163 patients (median age, 56years; interquartile range, 49-64years; 139 men) with HCCs were evaluated, of whom 27(16.6%) had histologically-confirmed iCNs. MRI identified 92.6% (25 of 27; 95% confidence interval [CI] 74.2%, 98.7%) of iCNs (sensitivity), with a specificity of 79.4% (78 of 136; 95% CI 71.4%, 85.7%), based on non-enhancement on post-contrast MRI. And the MRI-identified iCNs were characterized by a similar appearance to surrounding tumour tissue shown on pre-contrast MRI but not enhanced on post-contrast MRI. The multivariable Cox proportional hazards model revealed that only the presence of histologically-confirmed iCN was independently associated with early HCC recurrence (hazard ratio = 2.73; 95% CI 1.20, 6.21; P = 0.017). The Kaplan-Meier curve showed that the presence of MRI-identified iCN was also associated with early recurrence (P < 0.001). Multiparametric MRI identified iCNs with high sensitivity and modest specificity. The presence of iCNs is associated with early HCC recurrence.

Gross and Histopathological Dermal Changes at Sites of Snakebite – Report from Autopsy Series

Background: Snake bite remains a significant cause of accidental death, its occurrence usually underestimated because of under reporting.Objective: To report on gross and microscopic changes at sites of snakebite in autopsy.Methods: A cross-sectional, descriptive study was conducted on thirty cadavers of snake bite for study duration of one year based on inclusion and exclusion criteria. Skin was collected from sites of bite. Gross examination was carried out on formalin fixed specimens. Microscopic examination was performed on dermal biopsy of formalin fixed paraffin embedded sections stained with haematoxylene and eosin (H&amp;E).Results: 53.4% of deceased were in the age group of 41-50 years. Males were predominant in the study (90%) where 63.3% were agriculture workers. Lower limb bite was commonly seen (83.3%) in outdoor locales (90%). Snakes identified were cobra and viper. Death occurred within 48 hours of admission in 80% cases. Bite mark was visualised in ten cases and ulceration in three. Microscopic examination revealed normal epidermis in 53.3% cases. Abnormalities seen included acantholysis in 36.7% and ulceration in 10%cases. Dermal changes were coagulative necrosis (26.7%), fibrinoid necrosis (16.7%), haemorrhagic necrosis (20%), oedema (13.3%). Combination of changes in a particular case also observed. Vascular changes comprised of extravasation (30%), fibrinoid necrosis with microvascular damage (23.4%), vasculitis (13.3%), microvascular damage (26.7%). Perineural fibrosis, subcutaneous gangrenous and haemorrhagic fat necrosis were other observations.Conclusion: This study highlights histological profile of dermal changes by snake venom at site of bite that can enlighten its pathophysiologic effects on cutaneous tissue.International Journal of Human and Health Sciences Vol. 08 No. 02 Apr’24 Page: 132-139

Peculiarities of the ST-segment elevation myocardial infarction morphogenesis after mechanical restoration of epicardial blood flow without ECG signs of reperfusion

The aim of the study was to investigate the peculiarities of STEMI morphogenesis after mechanical restoration of epicardial blood flow without ECG signs of reperfusion. The autopsy data of 44 patients with STEMI who died at different times after PCI performed within the first 12 hours (27 cases), or 12–24 hours (17 cases), without ECG signs of reperfusion after the intervention, were analyzed. The comparison group consisted of 85 deceased without reperfusion therapy (RT). Histological examination of the myocardium was performed at following time: within 12 hours, at 13–24 hours, 2–4 days, 5–8 days, 9–15 and 16–22 days. The most common cause of death was acute left ventricular failure (ALVF) both in the group of blood flow restoration without ECG signs of reperfusion, and in the group without RT: 85 % and 79 %, respectively. In each of the two groups the number of deaths occurred in the first 12 hours exceeded one third, half of the patients died in the subsequent 12 hours, two thirds of the deaths occurred within further 2–3 days. The rates of risk factors: older age, anterior and recurrent myocardial infarction, three-vessel lesion of the coronary artery, and a large infarction area were similar in the two groups. From the first hours after PCI, the infarction zone was characterized by hemorrhagic imbibition, numerous injuries of the microcirculatory bed, by the signs of blood flow restoration in damaged vessels appeared from days 2–4, early manifestations of repair from days 5–7. In the MI group without PCI, the hemorrhagic demarcation started on days from 3–4, coagulation necrosis prevailed in the microvascular bed, signs of repair appeared at a later date. Multiple spasms and thromboses in the microvasculature may have been a response to a blood pressure drop that accompanies an acute decrease in the left ventricle contractile function caused by a large infarction area and/or unresolved complications arising during the interventions per se. This mechanism explains the rapid progression of left ventricular failure, the most common cause of death after the interventions with achieving the epicardial blood flow without ECG signs of reperfusion. The revealed microcirculation disorders reflect the absence of myocardial reperfusion, which is more prognostically significant than the restoration of epicardial blood flow.

Cooling Under a Blanketrol System Versus Cooling With an Arctic Sun Thermoregulation System (CATS) for Neonates Undergoing Therapeutic Hypothermia.

Background Despite evidence suggesting improved outcomes in neonates with hypoxic-ischemic encephalopathy (HIE) treated with therapeutic hypothermia (TH), data on the impact of temperature variability during cooling and its association with clinical outcomes remain limited. Objective To compare the efficacy and ease of use of two different cooling systems, the Arctic Sun (Medivance, Inc., Louisville, CO) vs. the Blanketrol III (Gentherm Medical, Cincinnati, OH) on achieving TH, temperature variability, and clinical outcomes in neonates with HIE undergoing TH. Methods This study was conducted at the Baylor Scott and White Medical Center's Level IV NICU. The study employed a retrospective cohort design, comparing infants treated with the Arctic Sun device (from December 2020 to August 2021) to a historical cohort treated with the Blanketrol system (from January 2017 to November 2020). Both groups were evaluated for clinical characteristics, patients' outcomes, and ease of use of the cooling devices. Ease of use was assessed through a self-developed survey administered to NICU nurses. Core body temperatures throughout the cooling course were documented at four-hour intervals, including induction, maintenance, and rewarming phases. Results Twenty-two infants were cooled using the Arctic Sun system, and 44 infants were cooled with the Blanketrol device. Median birth weight and gestational age were comparable. There were no significant differences in one-minute and five-minute appearance, pulse, grimace, activity, and respiration (APGAR) scores. The Arctic Sun group had a significantly higher rate of maternal morbidities, including diabetes and placental abruption. Although the median temperature achieved with both devices was 33.5°C, temperature variability was significantly greater with the Blanketrol device (p = 0.03). Thrombocytopenia rates were statistically different between the groups (9% in Arctic Sun vs. 38% in Blanketrol, p = 0.001). Although the Blanketrol group had higher rates of disseminated intravascular coagulation (48% vs. 37%), hypercalcemia (23% vs. 5%), and subcutaneous fat necrosis (7% vs. 5%), these differences were not statistically significant. A nurses' survey on ease of use revealed a strong preference for the Arctic Sun cooling system. Over 85% of nurses found it easier to learn and set up and required less manual intervention than the Blanketrol device. Conclusions Gel adhesive pad-based TH is a potentially superior modality to traditional water-circulating cooling devices. These pads offer advantages in user-friendliness, improved temperature control precision, and potentially reduced adverse event profiles.

Myocardial CD34+ Stromal Cells/Telocytes Demonstrate a Dynamic Pattern of Interactions with CD68+ Macrophages During Post-Myocardial Infarction Healing

Introduction: Myocardial CD34-positive (+) stromal cells/telocytes (SC/TCs) have been recently recognized as a novel type of resident cells involved in post-myocardial infarction (MI) repair. Alternatively, CD68-positive (+) macrophages are well-known constituents in this process. However, the relationship between these two cell populations remains mostly obscure. Therefore, this study was aimed to determine whether resident CD34+ SC/TCs and phagocytic CD68+ macrophages have any evident pattern of interactions during the inflammatory and proliferative phases of post-MI scar formation. Methods: A large transmural MI was induced in middle-aged male Sprague-Dawley rats (n = 15) under ketamine and xylazine anesthesia by permanent ligation of the left anterior descending coronary artery. The post-MI rats were infused with BrdU (5-bromo-2'-deoxyuridine) in a dose of 12.5 mg/kg/day for 72 hours via intraperitoneal osmotic minipumps on day 0, 4, or 11 after surgery. The rats were euthanized on day 3, 7 and 14 after MI, and their hearts were processed for histology and immunostaining. Results: On the third day after MI, CD34+ SC/TCs and CD68+ macrophages were absent within the core of the necrotic tissue, whereas both types of cells were juxtaposed in the space surrounding the area of coagulative necrosis. Furthermore, the presence of BrdU labeling in the nuclei of numerous CD34+ SC/TCs suggests their proliferation in the region of the active macrophage clearing. On the seventh day after MI, CD68+ macrophages were observed to have had advanced toward the center of the necrotic region leaving behind the area occupied primarily with acellular basement membranes from the resorbed CMs, whereas most of CD34+ SC/TCs trailed slightly behind. In part, such delay in centripetal progression of CD34+ SC/TCs through the areas of resorption could be attributed to the fact that these cells, in contrast to macrophages, often migrated along the acellular basement membranes left from the dead CMs that required phagocytic removal of necrotic debris to occur first. On the fourteenth day after MI, the population of CD68+ cells appeared notably reduced and demonstrated a patchy distribution predominantly along the remnants of the necrotic tissue. Meanwhile, the substantially expanded population of CD34+ SC/TCs were observed throughout the entire transmural scar, excluding the areas containing dead “mummified” CMs, aggregates of myofibroblasts and the fibroelastic thickening in subepicardial and subendocardial regions. Conclusion: Our findings, for the first time, demonstrate that populations of resident CD34+ SC/TCs and phagocytic CD68+ macrophages exhibit a dynamic pattern of interactions during early phases of post-MI scar formation, suggesting their importance in the process of post-ischemic myocardial healing. Supported by Camden Health Research Initiative. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Development of rabbit models of ventilator-associated bacterial pneumonia produced by carbapenem-resistant Pseudomonas aeruginosa.

Ventilator-associated bacterial pneumonia (VABP) is among the most intractable of carbapenem-resistant Gram-negative bacterial infections. New antimicrobial agents are critically needed for the treatment of VABP. However, current conventionally used animal model systems are inadequate to meet this challenge. We, therefore, developed rabbit models of VABP caused by carbapenem-resistant Pseudomonas aeruginosa. Persistently neutropenic New Zealand White rabbits were used throughout the study. The early-phase intubated model (0-24 h) received mechanical ventilation, while the late-phase intubated model (72-96 h) was ambulatory. The following outcome parameters were studied: survival, residual tissue bacterial burden (CFU/g), residual BAL bacterial burden (CFU/mL), lung weights, pulmonary lesion score, histology, O2 saturation, radiographic imaging, and histology. Each anesthetized rabbit received a predetermined endotracheal bacterial inoculum, and ventilators were set to FiO2 = 40% and PEEP = 8 mmHg. Within the first 12 h post-inoculation, mean bacterial burdens in lung tissue and BAL fluid, respectively, were established at approximately 107 CFU/g and 106 CFU/mL, persisted through 24 h in the early-phase model and increased in the late-phase model to approximately 108 CFU/g and 107 CFU/mL. Mean max SpO2 was ≥98 mmHg, and mean nadir SpO2 was ≥68 mmHg. Serial thoracic radiographs demonstrated progressive multilobar pneumonic infiltrates. Lung histology revealed progressive focal bronchopneumonia, coagulative necrosis, intra-alveolar hemorrhage, alveolar epithelial cell necrosis, and bacterial microcolonies. The new rabbit model of VABP produced by carbapenem-resistant Pseudomonas aeruginosa recapitulates the pathophysiological, microbiological, diagnostic imaging, and histological patterns of human disease by which to assess critically needed new antimicrobial agents against this lethal infection.

Thermocoagulation of resection surfaces of parenchymal organs using a new source of ultrahigh frequency energy (experimental study)

Relevance. Modern surgery is characterized by the use of various technical means to perform classical surgical techniques - separation and connection of tissues, hemostasis. The study of the applicability of new surgical devices and the search for technological techniques are an important task.The aim of the study: to evaluate the capabilities of the developed device based on microwave energy for hemostatic coagula­tion of resection surfaces of parenchymal organs.Materials and methods. The method is based on the principle of converting microwave energy into heat when it is absorbed in biological tissue. The choice of the microwave range is due to the higher efficiency of power supply to the heat­ing area. Based on the prototype of a medical microwave complex developed in 2011 for thermal effects on biological tissues (RF Patent 2481080. 2011), a prototype of a microwave coagulator for working with parenchymal organs was created. The device was tested on the paren­chymal organs of large laboratory animals under conditions of preserved and switched off blood flow in various energy supply modes. Tissue samples from coagulated lesions were studied histologically.Results. At the site of exposure of the applicator-coagulator to the parenchymal organ, a zone of coagulation changes appears. A clear dependence of the size of coagulation necrosis on the time and power of exposure was noted. When the blood flow is turned off, the necessary stable hemostasis is achieved by shorter exposure time of the coagulator antenna on the surface of the organ.Conclusions. The most effective and reliable hemostasis is achieved on the liver parenchyma. The use of temporary vascular isolation, especially on the kidneys and spleen, involves a single use of microwave energy to stop bleeding. By changing the power and duration of exposure, it is possible to dose the thermal load on biological tissue with great precision. This adjustment allows you to select the operating mode for each specific case. The obtained results of the experiment of the described system during surgery for the purpose of hemostasis in parenchymal bleeding.

Seromonitoring, Serotyping and Histopathology of Foot and Mouth Disease in Mithun (Bos Frontalis) in the Northeastern Hilly Terrain of India

Frequent FMD outbreaks have been one of the major challenges faced by the farmers and breeders of Mithun animals in Nagaland, owing to a lack of adequate knowledge and proper vaccination programs for the disease. Therefore, this study aimed to determine the extent of FMD serotype O virus infection, which is the most common serotype causing FMD specifically in the Mithun population in the northeastern state of Nagaland, India. In-vitro screening of serotype O virus antibodies in the blood serum of the Mithun population was carried out by ELISA kit. A total of 213 blood samples of Mithun animals were collected and screened where 67% of the samples tested were found to be positive and only 32% of the samples were found to be negative for the virus. All the samples collected from the neighbouring states of Mizoram and Arunachal Pradesh were found to be negative for the antibodies against the serotype O virus. Through m-RT PCR, O serotype was detected from all the clinically affected animals from the cells of the tongue epithelium, blood, and saliva of animals. During the histopathological studies, in the pericardium, severe interstitial myocarditis and liver showed focal areas of coagulative necrosis, focal necrosis, and pulmonary oedema were prominent and ballooning degeneration of epithelium in the tongue was evident in all cases. In conclusion, we were able to show the prevalence of FMDV serotype O antibodies in a very high percentage of the Mithun population that were tested along with pathological alterations, which should be addressed immediately with proper vaccination programs and by informing and educating the farmers and breeders about the disease before an outbreak occurs.

Experimental and Computational Analysis of High-Intensity Focused Ultrasound Thermal Ablation in Breast Cancer Cells: Monolayers vs. Spheroids.

High-intensity focused ultrasound (HIFU) is a non-invasive therapeutic modality that uses precise acoustic energy to ablate cancerous tissues through coagulative necrosis. In this context, we investigate the efficacy of HIFU ablation in two distinct cellular configurations, namely 2D monolayers and 3D spheroids of epithelial breast cancer cell lines (MDA-MB 231 and MCF7). The primary objective is to compare the response of these two in vitro models to HIFU while measuring their ablation percentages and temperature elevation levels. HIFU was systematically applied to the cell cultures, varying ultrasound intensity and duty cycle during different sonication sessions. The results indicate that the degree of ablation is highly influenced by the duty cycle, with higher duty cycles resulting in greater ablation percentages, while sonication duration has a minimal impact. Numerical simulations validate experimental observations, highlighting a significant disparity in the response of 2D monolayers and 3D spheroids to HIFU treatment. Specifically, tumor spheroids require lower temperature elevations for effective ablation, and their ablation percentage significantly increases with elevated duty cycles. This study contributes to a comprehensive understanding of acoustic energy conversion within the biological system during HIFU treatment for 2D versus 3D ablation targets, holding potential implications for refining and personalizing breast cancer therapeutic strategies.

Role of liver sinusoidal endothelial cell damage in the developmental process of hepatic sinusoidal obstruction syndrome: a focus on the research progress of immune inflammatory mechanisms

Hepatic sinusoidal obstruction syndrome (HSOS) is a type of secondary vascular disease of the liver that is mainly associated with the ingestion of pyrrole alkaloids (PAs) and hematopoietic stem cell transplantation (HSCT) treatment, resulting in severe liver dysfunction, multiple organ failure, and even death. Hepatic sinusoidal dilatation and obstruction, hepatocyte coagulative necrosis, and hepatic lobular inflammation are the main pathological manifestations of HSOS. The key initiating process for the pathogenesis of HSOS is damage to liver sinusoidal endothelial cells (LSECs). Currently, it is believed that LSECs are damaged by the involvement of multiple etiologies and mechanisms, and secondary coagulation and fibrinolysis disorders, oxidative stress, and inflammatory responses are the occurrence contributors to HSOS; however, the mechanism has not been fully elucidated. Therefore, the role of immune-inflammatory mechanisms has received increasing attention in LSEC damage. This article provides an overview of the epidemiology, etiology, and pathological changes of HSOS and reviews the physiological functions, common etiological damage mechanisms, and the key role of LSEC damage in the pathogenesis of HSOS, with a special focus on the role and research progress of immune-inflammatory mechanisms for LSEC damage in recent years. Furthermore, we believe that in-depth study and elucidation of the role of immune-inflammatory mechanisms in LSEC damage and the pathogenesis of HSOS and diagnosis will provide feasible research and development ideas for the screening and identification of new markers and drug treatment targets for HSOS.

The incidence, gross and histological features of Meckel’s diverticulum: A cadaveric study

: Meckel’s diverticulum (MD) develops from persistent omphalomesenteric duct and is an uncommon finding in females. Our aim is to report the incidence of finding of MD in cadavers and to study its gross and histological feature. : The observational study was conducted in 60 cadavers over a period of nine years. In the present study a meckel’s diverticulum was detected in sixty years old female cadaver. : The diverticulum was 63 cm proximal to ileocecal junction. It was 6 cm in length and 3.5cm in width and its tip free from any connections. Histologically, it showed four layers of ileum and patchy areas of coagulative necrosis in the mucosa.: These uneventful Meckel’s diverticulum findings of meckel’s diverticulum should be reported from time to time in particular population which may be beneficial for the surgeons and radiologists.

Experımental Study: The Effect Of 20% Intralıpıd Emulsıon Therapy In Cerebral Ischemıc Reperfusıon

ABSTRACT Background This experimental study was conducted to investigate the effect of 20% Intralipid Emulsion (ILE) treatment on Cerebral Ischemia Reperfusion Injury (CIRI) after reperfusion in acute ischemic stroke. Methods In this experimental study, seven rats without any intervention (control group), seven rats (sham group) for which CIRI was created after the common carotid artery was ligated for 2 hours, and seven rats who were treated with 20% ILE after CIRI (CIRI + ILE group) were sacrificed after 24 hours, and histopathological findings were investigated. Results In rats that were not treated after CIRI, 52.7% had level-1, 32.7% had level-2. and 14.5% had level-3. histopathological findings. While 72.2% of the rats treated with ILE had level-1 and 27.8% had level-2 findings, no level-3 histopathological findings were detected in any of the rats. While no signs of coagulative necrosis, spongiosis of surrounding tissue and polymorphonuclear leukocytes were observed histopathological in any of the rats given ILE, there was no macrophages finding in 85.6% of the rats. ILE treatment also reduced the histopathological findings of eosinophilic neurons, astrogliosis, neovascularization, vascular thrombosis and mononuclear inflammatory cells. Conclusion This study showed that 20% ILE treatment reduces the histopathological damage seen in cerebral ischemia and CIRI.

Luteolin Is a Potential Immunomodulating Natural Compound against Pulpal Inflammation.

The present study evaluated the therapeutic effects of luteolin in alleviating pulpitis of dental pulp- (DP-) derived microvesicles (MVs) via the inhibition of protein kinase R- (PKR-) mediated inflammation. Methodology. Proteomic analysis of immortalized human dental pulp (DP-1) cell-derived MVs was performed to identify PKR-associated molecules. The effect of luteolin on PKR phosphorylation in DP-1 cells and the expression of tumor necrosis factor-α (TNF-α) in THP-1 macrophage-like cells were validated. The effect of luteolin on cell proliferation was compared with that of chemical PKR inhibitors (C16 and 2-AP) and the unique commercially available sedative guaiacol-parachlorophenol. In the dog experimental pulpitis model, the pulps were treated with (1) saline, (2) guaiacol-parachlorophenol, and (3) luteolin. Sixteen teeth from four dogs were extracted, and the pulp tissues were analyzed using hematoxylin and eosin staining. Immunohistochemical staining was performed to analyze the expression of phosphorylated PKR (pPKR), myeloperoxidase (MPO), and CD68. Experimental endodontic-periodontal complex lesions were established in mouse molar through a silk ligature and simultaneous MV injection. MVs were prepared from DP-1 cells with or without pretreatment with 2-AP or luteolin. A three-dimensional microcomputed tomography analysis was performed on day 7 (n = 6). Periodontal bone resorption volumes were calculated for each group (nonligated-ligated), and the ratio of bone volume to tissue volume was measured. Proteomic analysis identified an endogenous PKR activator, and a protein activator of interferon-induced PKR, also known as PACT, was included in MVs. Luteolin inhibited the expressions of pPKR in DP-1 cells and TNF-α in THP-1 cells with the lowest suppression of cell proliferation. In the dog model of experimental pulpitis, luteolin treatment suppressed the expression of pPKR-, MPO-, and CD68-positive cells in pulp tissues, whereas guaiacol-parachlorophenol treatment caused coagulative necrosis and disruption. In a mouse model of endodontic-periodontal complex lesions, luteolin treatment significantly decreased MV-induced alveolar bone resorption. Luteolin is an effective and safe compound that inhibits PKR activation in DP-derived MVs, enabling pulp preservation.

Multifunctional Two-Dimensional Bi2Se3 nanodisks as a Non-Inflammatory photothermal agent for glioma treatment

Photothermal therapy (PTT) has gained widespread attention due to its significant advantages, such as noninvasiveness and ability to perform laser localization. However, PTT usually reaches temperatures exceeding 50 °C, which causes tumor coagulation necrosis and unfavorable inflammatory reactions, ultimately decreasing its efficacy. In this study, multifunctional two-dimensional Bi2Se3 nanodisks were synthesized as noninflammatory photothermal agents for glioma therapy. The Bi2Se3 nanodisks showed high photothermal stability and biocompatibility and no apparent toxicology. In addition, in vitro and in vivo studies revealed that the Bi2Se3 nanodisks effectively ablated gliomas at relatively low concentrations and inhibited tumor proliferation and migration. Moreover, the multienzymatic activity of the Bi2Se3 nanodisks inhibited the PTT-induced inflammatory response through their high ability to scavenge reactive oxygen species. Finally, the Bi2Se3 nanodisks demonstrated computed tomography capabilities for integrating diagnosis and treatment. These findings suggest that multifunctional Bi2Se3 nanodisk nanozymes can enable more effective cancer therapy and noninflammatory PTT.

Experimental study of the interstitial effect of a semiconductor laser with a wavelength of 445 nm on a biological model

Introduction. This study presents the results of interstitial exposure of a semiconductor laser with a wavelength of 445 nm to biological tissue samples at different pulsed wave power in a constant mode, with a contact method.Aim. To study the interstitial effect of a semiconductor laser with a wavelength of 445 nm on experimental tissue samples in a constant mode at different power.Materials and methods. As an experimental sample, we used biological tissue with a developed vascular structure in the form of pig liver. The source of laser radiation was a semiconductor laser with a wavelength of 445 nm, with a power range from 0.5 to 4 watts. When working with biological tissue samples, we evaluated their external and internal changes after laser exposure. The exposure time during interstitial exposure was 1 mm/sec with a 20 mm immersion depth of the laser fiber into the fabric. The results of the macro and microscopic picture were evaluated using histological examination and morphometry of the zones of destruction and coagulation necrosis, on a transverse section of the tissue.Results. The results of an experimental study indicate that interstitial laser exposure has a pronounced coagulation effect combined with a cutting effect. The optimal combination of coagulation and cutting effect of exposure, accompanied by visual contractility of the tissue, without excessive carbonation at a power of 3.0 watts.Conclusion. The use of interstitial exposure of a semiconductor laser with a wavelength of 445 nm on experimental tissue samples in a constant mode at different power showed the predominance of the coagulation effect in combination with the cutting effect with a pronounced reduction in tissue volume. Experiments have shown that the power of 3 W is the optimal power of laser exposure in the interstitial method, in which there is a pronounced reduction in the volume of the studied drug without excessive carbonation.

Skin Care Experience of a Case of Multiple Organ Failure Caused by High-Voltage Electrical Injury

Background: High-voltage electrical burns are caused by the direct transmission of electric current through the body and the conversion of electric energy into heat energy, which directly heats the tissues and leads to organ function damage. Especially after high-voltage electric burns (more than 1000W), it can not only cause coagulation necrosis of the skin and even carbonization, but also cause serious deep tissue damage .The degree of tissue damage depends on the type of current, the magnitude of current, the frequency, the voltage, the resistance of the tissue, the skin humidity, the duration, the contact area, and other factors. Low voltage and low frequency electric shock mainly affect the heart and respiration, which can lead to insignificant soft tissue damage. High voltage electric shock mainly causes serious soft tissue damage, which can be accompanied by changes in the circulatory system and respiratory system.[1] Subject and Method: We collected the data of a case of multiple organ failure caused by high-voltage electricity that was successfully treated in July 2023.In the course of this patient's successful treatment, The main nursing measures were analyzed: The intake and output volume were actively controlled. Albumin supplementation, Debridement and dressing change were performed daily, Covered with nano-silver ion dressing, Try to ensure a sterile environment during operation, Maintain ambient temperature and humidity. Results: Twenty days later,the skin damage caused by electric burns was reduced from 30% to 1%. Conclusion: These are very important links: The intake and output volume were actively controlled, The balance of intake and output was maintained for 24 hours, and lactic acid was less than 2mmol/L. Albumin supplementation Controlled above 30g/L, Debridement and dressing change were performed daily, Covered with nano-silver ion dressing, Try to ensure a sterile environment during operation, Maintain ambient temperature 28~30℃ and humidity 40%~50%.

Harnessing endoscopic ultrasound-guided radiofrequency ablation to reshape the pancreatic ductal adenocarcinoma microenvironment and elicit systemic immunomodulation.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by poor prognostics and substantial therapeutic challenges, with dismal survival rates. Tumor resistance in PDAC is primarily attributed to its fibrotic, hypoxic, and immune-suppressive tumor microenvironment (TME). Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA), an Food and Drug Administration (FDA)-approved minimally invasive technique for treating pancreatic cancer, disrupts tumors with heat and induces coagulative necrosis, releasing tumor antigens that may trigger a systemic immune response-the abscopal effect. We aim to elucidate the roles of EUS-RFA-mediated thermal and mechanical stress in enhancing anti-tumor immunity in PDAC. A comprehensive literature review focused on radiofrequency immunomodulation and immunotherapy in pancreatic tumors to understand the pathophysiological mechanisms of RFA and its effect on the TME, which could prevent recurrence and resistance. We reviewed clinical, preclinical, and in vitro studies on RFA mechanisms in pancreatic adenocarcinoma, discussing the unique immunomodulatory effects of EUS-RFA. Recent findings suggest that combining RFA with immune adjuvants enhances responses in pancreatic adenocarcinoma. EUS-RFA offers a dual benefit against PDAC by directly reducing tumor viability and indirectly enhancing anti-tumor immunity. Observations of neutrophil-mediated immunomodulation and programmed cell death ligand 1 (PD-L1) modulation support integrating EUS-RFA with targeted immunotherapies for managing pancreatic adenocarcinoma. Integrating EUS-RFA in PDAC treatment promises direct cytoreduction and synergistic effects with molecular targeted therapies. Prospective clinical trials are crucial to assess the efficacy of this combined approach in improving outcomes and survival rates in advanced PDAC cases.

Effects of Parallel Contact Cooling on Pulsed-Type, Bipolar Radiofrequency-Induced Tissue Reactions in an in vivo Porcine Model.

Skin cooling during laser or radiofrequency (RF) treatments is a method to minimize thermal damage to the epidermis, reduce pain, and decrease post-treatment downtime. We evaluated the effect of parallel contact cooling (PCC) on RF-induced thermal reactions in minipig skin in vivo after bipolar microneedling RF treatment. RF treatments were administered at frequencies of 0.5, 1, and 2 MHz with single (500 ms), six (1000 ms), and ten (5000 ms) sub-pulse packs to minipig skin with or without PCC. Subsequently, thermometric imaging and histology were used to analyze skin reactions to RF. Thermometric images showed that PCC promptly lowered skin temperature in the RF-treated area, with this effect persisting for over 60s. Regardless of the PCC, RF treatments lasting for 500 ms with a single pulse pack resulted in peri-electrode coagulative necrosis (PECN) zones and inter-electrode non-necrotic thermal reaction (IENT) zones in the dermis. In contrast, treatment lasting 5000 ms with 10 sub-pulse packs produced distinct IENT without notable PECN over a wide dermal area. Skin specimens obtained at 1 h and 3, 7, and 14 days after PCC-assisted RF treatments showed a higher degree of thermal tissue reactions in the deeper dermal regions compared to those after RF treatments without PCC. PCC-assisted RF treatment, utilizing an invasive bipolar microneedling device, enhanced RF-induced skin reactions in the mid to deep dermis while preserving the epidermis and upper papillary dermis from excessive thermal tissue injury.