Physical Techniques to Remove Residual Stone Fragments in the Urinary System.

BACKGROUND: Although significant progress has been made in treatment techniques for renal and ureteral calculi, residual fragments (RF) persisting long after treatment pose a serious threat to patients' health. A variety of novel physical techniques and extraction devices are currently being developed to promote the removal of RF from the urinary system, and a series of in vivo experiments have demonstrated their safety and efficacy. SUMMARY: External physical vibration lithecbole, magnetic extraction, biocompatible stone adhesive-based methods, and ultrasonic propulsion technologies are examples of innovative therapies that can promote the clearance of RF and improve the stone-free rate. In conclusion, the physical treatment of these RF needs to be optimized and improved. They are a promising technique for improving the efficiency of endovascular urology, and further in vivo studies are needed to confirm their safety and efficacy. KEY MESSAGES: We have summarized the literature on removal of RF by physical methods in recent years, especially the new progress.

Laparoscopic Radical Cystectomy With Ileal Orthotopic Neobladder for Bladder Cancer: Current Indications and Outcomes.

BACKGROUND: Laparoscopic radical cystectomy (LRC) with ileal orthotopic neobladder (IONB) reconstruction is one of the most promising methods for bladder cancer treatment; its advantages include a small incision size, less blood loss, improved perioperative outcome and tumor prognosis, and a positive self-image postoperatively. The short-term benefits of various IONB reconstruction procedures reported thus far include a simple process, short operative time, less intraoperative bleeding, few postoperative complications, and good postoperative neobladder function; in the long term, these benefits engender good quality of life of the patients. Here, we explored and summarized the more novel and available IONB reconstruction procedures to identify the safest, most efficient, and simplest IONB reconstruction techniques for patients with bladder cancer. SUMMARY: LRC with IONB reconstruction is technically feasible; however, most of the relevant studies have been short, employing a small sample size and a retrospective design. However, long-term, large-scale, prospective studies identifying the most appropriate bowel segments for IONB reconstruction, comparing intracorporeal and extracorporeal IONB reconstruction, assessing currently available IONBs, and resolving relevant postoperative complications further, with a focus on patients with bladder cancer, are warranted. KEY MESSAGE: Several procedures for LRC with IONB reconstruction have been reported thus far. However, there is no consensus regarding the IONB reconstruction procedures most beneficial to patients with bladder cancer. Our review may aid researchers in developing a simple, safe, and efficient LRC with IONB reconstruction procedure for patients with bladder cancer.

Clinical Safety and Efficacy of Locoregional Therapy Combined with Adoptive Transfer of Allogeneic γδ T Cells for Advanced Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma.

PURPOSE: To investigate the safety and efficacy of locoregional therapy plus adoptive transfer of allogeneic gamma delta (γδ) T cells for patients with hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). METHODS: Thirty patients with HCC and 29 patients with ICC were randomly assigned to receive locoregional therapy (HCC, Group A, n = 15; ICC, Group C, n = 15) or locoregional therapy plus γδ T cell therapy (HCC, Group B, n = 15; ICC, Group D, n = 14). Groups A and C only received locoregional ablation (cryoablation or irreversible electroporation), whereas Groups B and D received locoregional therapy followed by adoptive transfer of allogeneic γδ T cells. The primary endpoints were safety, distant progression-free survival (PFS), local PFS, and overall survival (OS). RESULTS: The median distant PFS was significantly longer in the combined treatment groups than the locoregional treatment groups (HCC: 8 vs 4 months, P = .04; ICC: 8 vs 4 months, P = .021). There was no significant difference in local PFS between the 2 treatment modalities. Patients with HCC in the combined treatment group had a longer OS (median OS: 13 vs 8 months, P = .029). However, there was no significant difference in OS in patients with ICC between the 2 treatment modalities (median OS: 9.5 vs 8 months, P = .546). All adverse events were manageable with no significant difference in incidence between groups. CONCLUSIONS: The novel combination of locoregional ablation with adoptive transfer of allogeneic γδ cells was safe, with encouraging clinical efficacy against HCC and ICC.

Efficacy and Safety of Percutaneous Argon-Helium Cryoablation for Hepatocellular Carcinoma Abutting the Diaphragm.

PURPOSE: To evaluate the efficacy and safety of percutaneous argon-helium cryoablation (CA) for hepatocellular carcinoma (HCC) abutting the diaphragm (<5 mm). MATERIALS AND METHODS: A total of 61 consecutive patients (50 men, 11 women; mean age, 56.3 ± 12.1 years old; range, 32-83 years) with 74 HCC tumors (mean size, 3.3 ± 1.7 cm; range, 0.8-7 cm) who were treated with percutaneous argon-helium CA were enrolled in this retrospective study. Adverse events were evaluated according to Common Terminology Criteria for Adverse Events, version 5.0. Local tumor progression (LTP) and overall survival (OS) were analyzed using the Kaplan-Meier method and the log-rank test. The risk factors associated with OS and LTP were evaluated using univariate and multivariate Cox regression analysis. RESULTS: No periprocedural (30-day) deaths occurred. A total of 29 intrathoracic adverse events occurred in 24 of the 61 patients. Major adverse events were reported in 5 patients (pleural effusion requiring catheter drainage in 4 patients and pneumothorax requiring catheter placement in 1 patient). Median follow-up was 18.7 months (range, 2.3-60.0 months). Median time to LTP after CA was 20.9 months (interquartile range [IQR], 14.1-30.6 months). Median times of OS after CA and diagnosis were 27.3 months (IQR, 15.1-45.1 months) and 40.9 months (interquartile range, 24.8-68.6 months), respectively. Independent prognostic factors for OS included tumor location (left lobe vs right lobe; hazard ratio [HR], 2.031; 95% confidence interval [CI], 1.062-3.885; P = .032) and number of intrahepatic tumors (solitary vs multifocal; HR, 2.684; 95% CI, 1.322-5.447; P = .006). Independent prognostic factors for LTP included age (HR, 0.931; 95% CI, 0.900-0.963; P  < .001), guidance modality (ultrasound vs computed tomography and US; HR, 6.156 95% CI, 1.862-20.348; P  =   .003) and origin of liver disease. CONCLUSIONS: Percutaneous argon-helium CA is safe for the treatment of HCC abutting the diaphragm, with acceptable LTP and OS.

The future of cryoablation: An abscopal effect.

Cryoablation has become a popular modality to treat a variety of malignant tumors in solid organs and soft tissues. In the future, the use of cryoablation should focus on its abscopal effect. The present review discusses the increased immune response triggered by cryoablation alone or by cryoablation combined with immunotherapies, which can improve the immune response and limit immunosuppression. First, cryoablative techniques should be improved to increase the area of necrosis and reduce the area of apoptosis. Second, cryoablation should be combined with immunotherapies, for example, cyclophosphamide, natural killer cells, granulocyte monocyte colony stimulating factor (GM-CSF), cytotoxic T lymphocyte-associated antigen (CTLA)-4, and programmed death receptor 1 (PD)-1 inhibitors. Cryoablation could also be combined with Hydrogen gas molecules, which were shown recently to stimulate peroxisome proliferator activated receptor gamma coactivator (PGC)-1α, thereby promoting mitochondrial function, which might rescue exhausted CD8+ T cells, leading to prolonged progression-free survival and overall survival of patients with advanced colorectal cancer.

Circulating Tumor DNA as a Sensitive Marker in Patients Undergoing Irreversible Electroporation for Pancreatic Cancer.

BACKGROUND/AIMS: Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed at an advanced stage, resulting in extremely poor 5-year survival. Late diagnosis of PDAC is mainly due to lack of a reliable method of early detection. Carbohydrate antigen (CA) 19-9 is often used as a tumor biomarker in PDAC; however, the test lacks sensitivity and specificity. Therefore, new sensitive and minimally invasive diagnostic tools are required to detect pancreatic cancer. METHODS: Here, we investigated circulating tumor DNA (ctDNA) which contained KRAS-mutated as a potential diagnostic tool for PDAC patients who underwent irreversible electroporation (IRE). We used droplet digital polymerase chain reaction (ddPCR) to detect the expression of KRAS-mutated genes in plasma samples of 65 PDAC patients who underwent IRE. RESULTS: In these 65 cases, ctDNA was detected in 20 (29.2%) samples. The median overall survival (OS) was 11.4 months with ctDNA+ patients and 14.3 months for ctDNA- patients. ctDNA+ patients had a obviously poorer prognosis associated to overall survival (P < 0.001). CONCLUSION: Our results suggested that the existence of ctDNA was a predictor of survival for PDAC patients. Therefore, ctDNA may be a new sensitive biomarker for monitoring treatment outcome in PDAC.

Allogenic Natural Killer Cell Immunotherapy Combined with Irreversible Electroporation for Stage IV Hepatocellular Carcinoma: Survival Outcome.

BACKGROUND/AIMS: We evaluated the clinical effectiveness of irreversible electroporation (IRE) in combination with immunotherapy using allogenic natural killer cells (NK) for stage IV hepatocellular carcinoma (HCC). METHODS: The study involved 40 patients with stage IV HCC who were divided equally into two groups: 1) simple IRE; and 2) IRE plus allogenic NK cells (IRE-NK); we mainly assessed the overall survival (OS). RESULTS: The effect of the IRE-NK treatment was synergistic, i.e., not only did it enhance immune function, it also decreased alpha-fetoprotein expression and showed significantly good clinical effectiveness. At the median 7.6-month follow-up (range, 3.8-12.1 months), median OS was higher in the IRE-NK group (10.1 months) than in the IRE group (8.9 months, P = 0.0078). CONCLUSION: IRE combined with allogeneic NK cell immunotherapy significantly increases the median OS of patients with stage IV HCC.

Irreversible electroporation for the treatment of rabbit VX2 breast cancer.

Irreversible electroporation (IRE) is considered predominantly as a non-thermal ablative technique that uses electrical fields to permeabilize cell membranes and lead to cell death. In this study, we evaluated the efficacy of IRE in the rabbit VX2 breast cancer model. Thirty-five female New Zealand white rabbits were inoculated against VX2 breast cancer cells. The rabbits were randomly divided into two groups: a control group of 15 rabbits and an IRE treatment group of 20 rabbits. Treatment and treatment outcome were evaluated by computerized tomography (CT) scan (plain or contrast enhanced), tumor growth curves and pathological examination including H&E, TUNEL, PCNA and CD31 staining. All rabbits in the IRE treatment group experienced successful IRE without obvious complications except for thoracic major muscle injury. A focused, complete and well-defined ablation zone where tumor cells have been thoroughly eradicated was detected by H&E staining, along with increasing TUNEL staining. The expression of PCNA and CD31 was down-regulated at the periphery of the ablation region. As of the last follow-up, 10 rabbits (67%) in IRE group demonstrated disease is under control; 2 rabbits (13%) are in stable condition; 3 rabbits (20%) suffered from disease progression; the remaining 5 rabbits were sacrificed for pathological examination halfway through the study. Overall, the efficacy of IRE was demonstrated by the creation of a complete ablation region, with increased apoptosis in the ablation zone and decreased proliferation and microvessel density of tumor tissue at the periphery. IRE is a promising local treatment for breast cancer.

Comparison between cryoablation and irreversible electroporation of rabbit livers at a location close to the gallbladder.

BACKGROUND: The ablation of liver tumors located close to the gallbladder is likely to lead to complications. The aim of this article is to compare the safety and efficacy of irreversible electroporation (IRE) and cryoablation in rabbit livers at a location close to the gallbladder. MATERIALS AND METHODS: We performed cryoablation (n = 12) and IRE (n = 12) of the area of the liver close to the gallbladder in 24 New Zealand white rabbits in order to ensure gallbladder damage. Serum aminotransferase and serum bilirubin levels were measured before and after the ablation. Histopathological examination of the ablation zones in the liver and gallbladder was performed on the 7th day after the ablation. RESULT: Seven days after the ablation, all 24 animals were alive. Gallbladder perforation did not occur in the IRE group; only mucosal epithelial necrosis and serous layer edema were found in this group. Gallbladder perforation occurred in four rabbits in the cryoablation group. Serum aminotransferase and serum bilirubin levels obviously increased in both groups by Day 3 and decreased gradually thereafter. The elevation in aminotransferase and bilirubin levels was greater in the cryoablation group than the IRE group. Pathological examination revealed complete necrosis of the liver parenchyma from the ablation center to the gallbladder in both groups, but bile duct and granulation tissue hyperplasia were observed in only the IRE group. Full-thickness gallbladder-wall necrosis was seen in the cryoablation group. CONCLUSIONS: For ablation of the liver area near the gallbladder, IRE is superior to cryoablation, both in terms of safety (no gallbladder perforation in the IRE group) and efficacy (complete necrosis and rapid recovery in the IRE group).

Comparison of percutaneous cryoablation with microwave ablation in a porcine liver model.

We compared imaging and pathological changes between argon-helium cryosurgical (AH) and microwave (MW) ablation in a porcine liver model. Immediately after ablation, computed tomography (CT) imaging showed that the area affected by MW ablation was considerably greater than that affected by AH ablation; moreover, the surface area of necrotic tissue was considerably greater in the AH group, whereas the depth of the necrotic area was similar. Seven days after ablation, the affected area had not changed much in the AH group, but it had significantly increased in the MW group; similarly, the surface and depth of the necrotic areas had not changed much in the AH group, but they had increased significantly in the MW group. The pathological findings showed similar definitive areas for both groups at both time points. The findings indicated that long time after both therapies, complete tissue necrosis can be achieved, but the extent and depth of necrosis differ: necrosis foci after AH ablation could be predicted by ice ball under CT image, and necrosis foci after MW ablation will increase obviously. MW ablation might therefore be suitable for tumors with a larger volume and simple anatomical structures, and AH ablation might be suitable for tumors with complex anatomical structures or those located near important organs. These two methods could therefore be used in combination in clinical settings, but details of the procedure need to be studied.

Cryotherapy for local recurrent dermatofibrosarcoma protuberans: experience in 19 patients.

Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive, cutaneous, malignant tumor characterized by a high propensity for local relapse. Wide and deep local excision with reconstructive surgery is the current standard therapy for DFSP, with a local recurrence rate (LRR) of nearly 40%. In this study, we cured 19 patients with local recurrence of DFSP with 39 sessions of percutaneous cryoablation performed between July 2004 and August 2008. The LRRs after one, two and three cryosurgery sessions per patient were 68%, 54% and 0%, respectively. Moreover, the LRR did not differ with tumor location or size. Furthermore, all patients had a progression-free survival of >5 years. Only minor complications such as fever, local edema, mild nerve injury and local pain occurred, and were resolved within 1 week with symptomatic treatment. In our experience, percutaneous cryoablation is a relatively safe and efficient technique for the treatment of local recurrence of DFSPs.

Cryoprotective therapy for huge hepatocellular carcinoma: a study of 14 patients with a single lesion.

Percutaneous cryoablation is a potential cure for hepatocellular carcinoma (HCC). This study reviewed retrospectively clinical data from 14 patients who underwent cryoablation of huge HCC (long diameter >7 cm). The side effects of cryosurgeries and liver function reverse were recorded and compared everyday. All the patients survived cryosurgery and none died before leaving hospital 2 weeks later. Despite liver-protective treatment before cryosurgery, alanine transaminase (ALT) and aspartate transaminase (AST) levels were increased significantly, but returned to preoperative levels 2 weeks post-cryosurgery. Before cryosurgery, mean total bilirubin (T.BIL) and direct bilirubin (D.BIL) levels were normal; 8-10 days after cryosurgery, they increased more than two-fold, but returned to the preoperative level 2 weeks post-cryosurgery. Serum transaminase and bilirubin levels were compared between hepatitis B positive and negative patients. The hepatitis B negative group's AST level increased significantly 1 day post-cryosurgery (mean, 186 U/L) and decreased to the preoperative level at day 14. In the hepatitis B positive group, means transaminase and bilirubin reached peak values at different days post-cryosurgery. Overall, ALT and AST are valuable indicators of liver function impairment following cryosurgery. In patients with hepatitis B virus, close attention to the serum bilirubin level should be paid 8-10 days after cryosurgery. Liver-protective treatment may alleviate liver function impairment caused by cryosurgery of huge HCC.

Thermal Fatigue Failure of Micro-Solder Joints in Electronic Packaging Devices: A Review.

In electronic packaging products in the service process, the solder joints experience thermal fatigue due to temperature cycles, which have a significant influence on the performance of electronic products and the reliability of solder joints. In this paper, the thermal fatigue failure mechanism of solder joints in microelectronic packages, the microstructure changes of the thermal fatigue process, the influence factors on the joint fatigue life, and the simulation analysis and forecasting of thermal fatigue life are reviewed. The results show that the solder joints are heterogeneously coarsened, and this leads to fatigue cracks occurring under the elevated high-temperature phase of alternating temperature cycles. However, the thickness of the solder and the hold time in the high-temperature phase do not significantly influence the thermal fatigue. The coarsened region and the IMC layer thicken with the number of cycles, and the cracks initiate and propagate along the interface between the intermetallic compound (IMC) layer and coarsened region, eventually leading to solder joint failure. For lead-containing and lead-free solders, the lead-containing solder shows a faster fatigue crack growth rate and propagates by transgranular mode. Temperature and frequency affect the thermal fatigue life of solder joints to different degrees, and the fatigue lifetime of solder joints can be predicted through a variety of methods and simulated crack trajectories, but also through the use of a unified constitutive model and finite element analysis for prediction.

Pressureless Immersion of Epoxy Resin-Filled Cracks in Faulted Rock Materials.

Epoxy resin, known for its excellent corrosion resistance, water resistance, and high-temperature resistance, is extensively utilized in construction and water-related projects. Within water conservancy projects, natural factors such as water impact and weathering often result in cracks within rock formations. Consequently, the application of epoxy resin materials for repair and reinforcement has emerged as a common solution. This research investigates the impact of five epoxy grouting materials, YDS (100:6.4), RH-1 (6.1:1), PSI (9:1), TK (100:8), and HK-G (5:1), on the repair and reinforcement of faulted rock at the Yebatan Hydropower Station. Penetration experiments were conducted on rock samples, and the strength of the epoxy grout samples was tested under ambient conditions of 20 °C, 15 °C, and 0 °C. The experimental results indicate that all five epoxy grout materials successfully penetrated the faulted rock samples. Among them, the PSI (9:1) epoxy grouting material exhibited the most exceptional reinforcing effect across different temperatures, with grouting samples demonstrating strengths in the range of 20 to 25 MPa. This paper confirms that epoxy resin effectively repairs and reinforces rock structures, thereby enhancing the safety and durability of water conservancy projects.

Application of additively manufactured bone scaffold: a systematic review.

The application of additive manufacturing (AM) technology plays a significant role in various fields, incorporating a wide range of cutting-edge technologies such as aerospace, medical treatment, electronic information, and materials. It is currently widely adopted for medical services, national defense, and industrial manufacturing. In recent years, AM has also been extensively employed to produce bone scaffolds and implant materials. Through AM, products can be manufactured without being constrained by complex internal structures. AM is particularly advantageous in the production of macroscopically irregular and microscopically porous biomimetic bone scaffolds, with short production cycles required. In this paper, AM commonly used to produce bone scaffolds and orthopedic implants is overviewed to analyze the different materials and structures adopted for AM. The applications of antibacterial bone scaffolds and bone scaffolds in biologically relevant animal models are discussed. Also, the influence on the comprehensive performance of product mechanics, mass transfer, and biology is explored. By identifying the reasons for the limited application of existing AM in the biomedical field, the solutions are proposed. This study provides an important reference for the future development of AM in the field of orthopedic healthcare. In conclusion, various AM technologies, the requirements of bone scaffolds and the important role of AM in building bridges between biomaterials, additives, and bone tissue engineering scaffolds are described and highlighted. Nevertheless, more caution should be exercised when designing bone scaffolds and conducting in vivo trials, due to the lack of standardized processes, which prevents the accuracy of results and reduces the reliability of information.

Influence of oxygen content on selective laser melting leading to the formation of spheroidization in additive manufacturing technology.

Selective laser melting (SLM) additive manufacturing technology with different oxygen contents leads to the appearance of spherical solids of different sizes on the surface of the part, which affects the mechanical properties of the part, surface roughness, etc. In this study, the SLM molding technique was applied using three different 316L metal powders with different oxygen contents. The spheroidization properties and morphology of the samples were observed using a Quanta 200 environmental scanning electron microscope (ESEM), and the samples were observed microscopically and subjected to EDX spectroscopy using metallographic microscopy, and the mechanical properties were investigated. The results of the study showed that when using gas atomized powders, no spheroidization occurred when the oxygen content of the powders was 5.44 ± 0.01% in all cases, whereas using water atomized powders produced spherical structures with larger dimensions. This observation was closely related to the shape and particle size of the powder. When 316L metal powder with an oxygen content of 4.52 ± 0.01% was used for molding, small spherical structures appeared on the surface of the samples. When metal powder with an oxygen content of 5.44 ± 0.01% was used for the molding, larger spherical structures appeared on the surface of the samples. When the powder with an oxygen content of 5.90 ± 0.01% was used for the molding, more small spherical structures and some large spherical structures appeared on the surface of the samples. This suggests that higher oxygen levels may inhibit the occurrence of spheroidization. EDX spectroscopic analysis revealed that the white matter on the surface of the samples without spheroidization was mainly composed of Fe and Cr, whereas the white matter on the surface of the large-sized spherical structures was mainly composed of Si and Mn, which may be related to the oxygenophilicity of the various substances.

Immunotherapy for renal cell carcinoma: New therapeutic combinations and adverse event management strategies: A review.

Immune checkpoint inhibitor (ICI) combinations, as well as ICIs combined with tyrosine kinase inhibitors, have considerable potential for renal cell carcinoma (RCC) treatment. Newer targeted medications, gut microbiome, nanomedicines, and cyclin-dependent kinase (CDK) inhibitors demonstrate significant potential in preventing side effects and resistance associated with RCC treatment. Most patients, including those demonstrating long-term treatment effects, eventually demonstrate cancer progression. Nevertheless, recent studies have further revealed RCC pathogenesis and many acquired drug resistance mechanisms, which together have led to the identification of promising therapeutic targets. In addition to having roles in metabolism, immunogenicity, and the immune response to tumors, CDK4 and CDK6 regulate the cell cycle. Targeting CDK4 and CDK6, either separately or in combination with already approved treatments, may improve therapeutic outcomes in patients with kidney cancer. Other novel drugs, including pegylated interleukin 10, colony-stimulating factor 1 receptor inhibitors, CD40 agonists, and C-X-C receptor 4 inhibitors affect the tumor microenvironment and cancer cell metabolism. Moreover, a triple ICI combination has been noted to be efficacious. In general, compared with sunitinib as a single-drug treatment, newer ICI combinations improve overall survival in patients with RCC. Future research on the prevention of adverse events and medication resistance related to newer therapies may aid in ensuring effective treatment outcomes among patients with RCC. This article aims to summarize innovative immunotherapy drug combinations for RCC treatment and the mechanisms of action, drug resistance, and treatment of adverse events associated with these combinations.

Advances in the study of gastric organoids as disease models.

Gastric organoids are models created in the laboratory using stem cells and sophisticated three-dimensional cell culture techniques. These models have shown great promise in providing valuable insights into gastric physiology and advanced disease research. This review comprehensively summarizes and analyzes the research advances in culture methods and techniques for adult stem cells and induced pluripotent stem cell-derived organoids, and patient-derived organoids. The potential value of gastric organoids in studying the pathogenesis of stomach-related diseases and facilitating drug screening is initially discussed. The construction of gastric organoids involves several key steps, including cell extraction and culture, three-dimensional structure formation, and functional expression. Simulating the structure and function of the human stomach by disease modeling with gastric organoids provides a platform to study the mechanism of gastric cancer induction by Helicobacter pylori. In addition, in drug screening and development, gastric organoids can be used as a key tool to evaluate drug efficacy and toxicity in preclinical trials. They can also be used for precision medicine according to the specific conditions of patients with gastric cancer, to assess drug resistance, and to predict the possibility of adverse reactions. However, despite the impressive progress in the field of gastric organoids, there are still many unknowns that need to be addressed, especially in the field of regenerative medicine. Meanwhile, the reproducibility and consistency of organoid cultures are major challenges that must be overcome. These challenges have had a significant impact on the development of gastric organoids. Nonetheless, as technology continues to advance, we can foresee more comprehensive research in the construction of gastric organoids. Such research will provide better solutions for the treatment of stomach-related diseases and personalized medicine.

Echinatin mitigates sevoflurane-induced neurotoxicity through regulation of ferroptosis and iron homeostasis.

Surgery and anesthesia are vital medical interventions, but concerns over their potential cognitive side effects, particularly with the use of inhalational anesthetics like sevoflurane, have surfaced. This study delves into the neuroprotective potential of Echinatin against sevoflurane-induced neurotoxicity and the underlying mechanisms. Echinatin, a natural compound, has exhibited anti-inflammatory, antioxidant, and anticancer properties. Sevoflurane, while a popular anesthetic, is associated with perioperative neurocognitive disorders (PND) and neurotoxicity. Our investigation began with cellular models, where Echinatin demonstrated a significant reduction in sevoflurane-induced apoptosis. Mechanistically, we identified ferroptosis, a novel form of programmed cell death characterized by iron accumulation and lipid peroxidation, as a key player in sevoflurane-induced neuronal injury. Echinatin notably suppressed ferroptosis in sevoflurane-exposed cells, suggesting a pivotal role in neuroprotection. Expanding our research to a murine model, we observed perturbations in iron homeostasis, inflammatory cytokines, and antioxidants due to sevoflurane exposure. Echinatin treatment effectively restored iron balance, mitigated inflammation, and preserved antioxidant levels in vivo. Behavioral assessments using the Morris water maze further confirmed Echinatin's neuroprotective potential, as it ameliorated sevoflurane-induced spatial learning and memory impairments. In conclusion, our study unveils Echinatin as a promising candidate for mitigating sevoflurane-induced neurotoxicity. Through the regulation of ferroptosis, iron homeostasis, and inflammation, Echinatin demonstrates significant neuroprotection both in vitro and in vivo. These findings illuminate the potential for Echinatin to enhance the safety of surgical procedures involving sevoflurane anesthesia, minimizing the risk of cognitive deficits and neurotoxicity.

Irinotecan combined with co-stimulatory molecule blockade prolongs survival of cardiac allografts in alloantigen-primed mice.

Memory T cells play an important role in graft rejection. In this study, we investigated the potential effect of Irinotecan (CPT-11), a topoisomerase I inhibitor used in the treatment of a variety of solid tumor malignancies, on memory T cells. CPT-11 treatment alone or combined with blocking monoclonal antibodies (mAb) against co-stimulatory molecules (LFA-1 and CD154) was evaluated in the prevention of heart transplant rejection in alloantigen-primed mice. Our data suggest that CPT-11 reduced the expression of IL-2/IFN-γ and increased IL-10/TGF-ß expression in both peripheral blood and within the grafts. CPT-11 could also inhibit alloresponses of memory T cells, while decreasing the proportion of CD4(+) memory T cells in the spleen of the recipients and significantly reducing serum alloantibody levels. Our study highlights obvious synergistic effects of CPT-11 when combined with co-stimulatory molecule blockade in prolonging the survival of cardiac allografts in alloantigen-primed mice.