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.

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.

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.

Design and Optimization of Heat Treatment Process Parameters for High-Molybdenum-Vanadium High-Speed Steel for Rolls.

High-molybdenum-vanadium high-speed steel is a new type of high-hardenability tool steel with excellent wear resistance, castability, and high-temperature red hardness. This paper proposes a composition design of high-molybdenum-vanadium high-speed steel for rolls, and its specific chemical composition is as follows (wt.%): C2%, Mo7.0%, V7.0%, Si0.3%, Mn0.3%, Ni0.4%, Cr3.0%, and the rest of the iron. This design is characterized by the increase in molybdenum and vanadium in high-speed steel to replace traditional high-speed steel rolls with the tungsten element in order to reduce the heavy elements' tungsten-specific gravity segregation caused by centrifugal casting so that the roll performance is uniform and the stability of use is improved. JMatPro (version 7.0) simulation software is used for the composition design of high-molybdenum-vanadium high-speed steel. The phase composition diagram is analyzed under different temperatures. The content of different phases of the organization in different temperatures is also studied. The martensitic transformation temperature and different tempering temperatures with the different types of compounds and grain sizes are calculated. The process parameters of heat treatment of high-molybdenum-vanadium high-speed steel are optimized. The selection of carbon content and the temperature of M50 are calculated and optimized, and the results show that the range of pouring temperatures, quenching temperatures, annealing temperatures, and tempering temperatures are 1360~1410 °C, 1190~1200 °C, 818~838 °C, and 550~600 °C, respectively. Scanning electron microscope (SEM) analysis of the samples obtained by using the above heat treatment parameters is consistent with the simulation results, which indicates that the simulation has important reference significance for guiding the actual production.

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.

Exosomal microRNA Therapy for Non-Small-Cell Lung Cancer.

With the progress of molecular diagnosis research on non-small cell lung cancer (NSCLC) cells, four identified categories of microRNAs have been found to be related to disease diagnosis, diagnosis of treatment resistance, prediction of prognosis, and drugs for treatment. To date, nine target mRNA/signal pathways have been confirmed for microRNA drug therapy both in vitro and in vivo. When microRNA drugs enter blood vessels, they target the tumor site and play a similar role to that of targeted drugs. However, whether they will produce serious off-target effects remains unknown, and further clinical research is needed. This review provides the first summary of microRNA therapy for NSCLC.

Subcutaneous device-free islet transplantation.

Diabetes mellitus is a chronic metabolic disease, characterized by high blood sugar levels; it affects more than 500 million individuals worldwide. Type 1 diabetes mellitus (T1DM) is results from insufficient insulin secretion by islets; its treatment requires lifelong use of insulin injections, which leads to a large economic burden on patients. Islet transplantation may be a promising effective treatment for T1DM. Clinically, this process currently involves directly infusing islet cells into the hepatic portal vein; however, transplantation at this site often elicits immediate blood-mediated inflammatory and acute immune responses. Subcutaneous islet transplantation is an attractive alternative to islet transplantation because it is simpler, demonstrates lower surgical complication risks, and enables graft monitoring and removal. In this article, we review the current methods of subcutaneous device-free islet transplantation. Recent subcutaneous islet transplantation techniques with high success rate have involved the use of bioengineering technology and biomaterial cotransplantation-including cell and cell growth factor co-transplantation and hydrogel- or simulated extracellular matrix-wrapped subcutaneous co-transplantation. In general, current subcutaneous device-free islet transplantation modalities can simplify the surgical process and improve the posttransplantation graft survival rate, thus aiding effective T1DM management.

Protective effects of Chinese herbal monomers against ischemia-reperfusion injury.

OBJECTIVES: Ischemia-reperfusion injury is a complicated pathologic process that involves multiple factors including oxidative stress, endoplasmic reticulum stress, calcium overload, inflammatory response, disturbances in energy metabolism, apoptosis, and some newly-described forms of programmed cell death (e.g., necroptosis, autophagy, pyroptosis, patanatos, and ferroptosis). Chinese herbal monomers (CHMs) have long been applied to treat ischemia-reperfusion injury based on a solid research foundation. This paper objectively reviews in vitro and in vivo studies on the use of CHMs to protect against ischemia-reperfusion injury. METHODS: We reviewed 31 CHMs that have been shown to be effective for treating ischemia-reperfusion injury models of the heart, brain, and kidney. According to the mechanism of action, these CHMs were divided into three categories: protecting damaged histocytes, inhibiting inflammatory cells, and promoting the proliferation of damaged histocytes. Some CHMs were found to have more than one mechanism at the same time. RESULTS: Of the 31 CHMs, 28 protect damaged histocytes, 13 inhibit inflammatory cells, and three promote the proliferation of damaged histocytes. CONCLUSIONS: CHMs show promise for treating ischemia-reperfusion injury. The eexisting treatment experiences for ischemia-reperfusion injury can be used as a reference.

Research on Characterization of Nylon Composites Functional Material Filled with Al2O3 Particle.

This study revolves around the issues raised by the current semiconductor device metal casings (mainly composed of aluminum and its alloys), such as resource and energy consumption, complexity of the production process, and environmental pollution. To address these issues, researchers have proposed an eco-friendly and high-performance alternative material-Al2O3 particle-filled nylon composite functional material. This research conducted detailed characterization and analysis of the composite material through scanning electron microscopy (SEM) and differential scanning calorimetry (DSC). The results show that the Al2O3 particle-filled nylon composite material has a significantly superior thermal conductivity, about twice as high as that of pure nylon material. Meanwhile, the composite material has good thermal stability, maintaining its performance in high-temperature environments above 240 °C. This performance is attributed to the tight bonding interface between the Al2O3 particles and the nylon matrix, which not only improves the heat transfer efficiency but also significantly enhances the material's mechanical properties, with a strength of up to 53 MPa. This study is of great significance, aiming to provide a high-performance composite material that can alleviate resource consumption and environmental pollution issues, with excellent polishability, thermal conductivity, and moldability, which is expected to play a positive role in reducing resource consumption and environmental pollution problems. In terms of potential applications, Al2O3/PA6 composite material can be widely used in heat dissipation components for LED semiconductor lighting and other high-temperature heat dissipation components, thereby improving product performance and service life, reducing energy consumption and environmental burden, and laying a solid foundation for the development and application of future high-performance eco-friendly materials.

Study of the Solder Characteristics of IGBT Modules Based on Thermal-Mechanical Coupling Simulation.

The insulated-gate bipolar transistor (IGBT) represents a crucial component within the domain of power semiconductor devices, which finds ubiquitous employment across a range of critical domains, including new energy vehicles, smart grid systems, rail transit, aerospace, etc. The main characteristics of its operating environment are high voltage, large current, and high power density, which can easily cause issues, such as thermal stress, thermal fatigue, and mechanical stress. Therefore, the reliability of IGBT module packaging has become a critical research topic. This study focuses on the damage of power device solder layers and applies heat transfer theory. Three typical solders for welding IGBTs (92.5Pb5Sn2.5Ag, Sn3.0Ag0.5Cu (SAC305), and nano-silver solder paste) are analyzed using JMatPro software to simulate their characteristics. First, a finite element analysis method is used to simulate the entire IGBT module with ANSYS Workbench platform. The study compares the impact of three types of solders on the overall heat transfer of the IGBT module under normal operation and welding layer damage conditions. The characteristics are analyzed based on changes in the junction temperature, heat flow path, and the law of thermal stress and deformation. The findings indicated that under steady-state working conditions, adjacent chips in a multi-chip IGBT module had significant thermal coupling, with a maximum temperature difference between chip junctions reaching up to 13 °C, and a phenomenon of heat concentration emerged. The three types of solders could change the thermal conductivity and heat transfer direction of the IGBT module to varying degrees, resulting in a temperature change of 3-6 °C. Under conditions of solder layer damage, the junction temperature increased linearly with the severity of the damage. In the 92.5Pb5Sn2.5Ag and Sn3.0Ag0.5Cu (SAC305) solders, the presence of intermetallic compounds (IMCs) led to more stress concentration points in the solder layer, with the maximum stress reaching 7.14661 × 107 MPa and concentrated at the edge of the solder layer. The nano-silver solder layer had the best thermal conductivity, and the maximum thermal deformation under the same conditions was only 1.9092 × 10-5 m.

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.

High-flow hydrogen inhalation might suppresses the immune function of middle-aged participants: a self-controlled study.

Hydrogen inhalation therapy has been proven to be safe and effective in disease treatment in multiple clinical reports, but the gas flow rates used in different studies vary greatly. Since there is no upper limit for the safe concentration of hydrogen, this study tested the effects of high-flow (not high concentration) hydrogen inhalation on immune function. From October 2019 to January 2020, 20 adult participants (31-60 years old) were enrolled in a self-controlled study to check the immune function in peripheral blood lymphocyte subsets before and after a 2-week hydrogen inhalation protocol. The participants inhaled hydrogen for 2 or 4 hours each day. After 2 weeks of hydrogen inhalation, statistically significant changes were observed in follicular helper T cells, helper and cytotoxic T cells, natural killer and natural killer T cells, and gamma delta T cells, generally suggesting a decrease in their proportions. These results show that high-flow hydrogen inhalation has an inhibitory effect on the immune function of healthy participants. The study protocol received ethical approval from the Ethics Committee of Fuda Cancer Hospital, Jinan University on December 7, 2018 (approval No. Fuda20181207).

Allogeneic Vγ9Vδ2 T-cell immunotherapy exhibits promising clinical safety and prolongs the survival of patients with late-stage lung or liver cancer.

Vγ9Vδ2 T cells are promising candidates for cellular tumor immunotherapy. Due to their HLA-independent mode of action, allogeneic Vγ9Vδ2 T cells can be considered for clinical application. To apply allogeneic Vγ9Vδ2 T cells in adoptive immunotherapy, the methodology used to obtain adequate cell numbers with optimal effector function in vitro needs to be optimized, and clinical safety and efficacy also need to be proven. Therefore, we developed a novel formula to improve the expansion of peripheral γδ T cells from healthy donors. Then, we used a humanized mouse model to validate the therapeutic efficacy of expanded γδ T cells in vivo; furthermore, the expanded γδ T cells were adoptively transferred into late-stage liver and lung cancer patients. We found that the expanded cells possessed significantly improved immune effector functions, including proliferation, differentiation, and cancer cell killing, both in vitro and in the humanized mouse model. Furthermore, a phase I clinical trial in 132 late-stage cancer patients with a total of 414 cell infusions unequivocally validated the clinical safety of allogeneic Vγ9Vδ2 T cells. Among these 132 patients, 8 liver cancer patients and 10 lung cancer patients who received ≥5 cell infusions showed greatly prolonged survival, which preliminarily verified the efficacy of allogeneic Vγ9Vδ2 T-cell therapy. Our clinical studies underscore the safety and efficacy of allogeneic Vγ9Vδ2 T-cell immunotherapy, which will inspire further clinical investigations and eventually benefit cancer patients.

Gemcitabine plus concurrent irreversible electroporation vs gemcitabine alone for locally advanced pancreatic cancer.

BACKGROUND: Locally advanced pancreatic cancer (LAPC) is a common malignant digestive system tumor that ranks as the fourth leading cause of cancer-related death in the world. The prognosis of LAPC is poor even after standard treatment. Irreversible electroporation (IRE) is a novel ablative strategy for LAPC. Several studies have confirmed the safety of IRE. To date, no prospective studies have been performed to investigate the therapeutic efficacy of conventional gemcitabine (GEM) plus concurrent IRE. AIM: To compare the therapeutic efficacy between conventional GEM plus concurrent IRE and GEM alone for LAPC. METHODS: From February 2016 to September 2017, a total of 68 LAPC patients were treated with GEM plus concurrent IRE n = 33) or GEM alone n = 35). Overall survival (OS), progression free survival (PFS), and procedure-related complications were compared between the two groups. Multivariate analyses were performed to identify any prognostic factors. RESULTS: There were no treatment-related deaths. The technical success rate of IRE ablation was 100%. The GEM + IRE group had a significantly longer OS from the time of diagnosis of LAPC (19.8 mo vs 9.3 mo, P < 0.0001) than the GEM alone group. The GEM + IRE group had a significantly longer PFS (8.3 mo vs 4.7 mo, P < 0.0001) than the GEM alone group. Tumor volume less than 37 cm3 and GEM plus concurrent IRE were identified as significant favorable factors for both the OS and PFS. CONCLUSION: Gemcitabine plus concurrent IRE is an effective treatment for patients with LAPC.

Two weeks of hydrogen inhalation can significantly reverse adaptive and innate immune system senescence patients with advanced non-small cell lung cancer: a self-controlled study.

Following standard treatments, the traditional model for enhancing anti-tumor immunity involves performing immune reconstitution (e.g., adoptive immune cell therapies or immunoenhancing drugs) to prevent recurrence. For patients with advanced non-small cell lung cancer, we report here on two objectives, the immunosenescence for advanced non-small cell lung cancer and hydrogen gas inhalation for immune reconstitution. From July 1st to September 25th, 2019, 20 non-small cell lung cancer patients were enrolled to evaluate the immunosenescence of peripheral blood lymphocyte subsets, including T cell, natural killer/natural killer T cell and gamma delta T cell. Two weeks of hydrogen inhalation was performed during the waiting period for treatment-related examination. All patients inhaled a mixture of hydrogen (66.7%) and oxygen (33.3%) with a gas flow rate of 3 L/min for 4 hours each day. None of the patients received any standard treatment during the hydrogen inhalation period. After pretreatment testing, major indexes of immunosenescence were observed. The abnormally higher indexes included exhausted cytotoxic T cells, senescent cytotoxic T cells, and killer Vδ1 cells. After 2 weeks of hydrogen therapy, the number of exhausted and senescent cytotoxic T cells decreased to within the normal range, and there was an increase in killer Vδ1 cells. The abnormally lower indexes included functional helper and cytotoxic T cells, Th1, total natural killer T cells, natural killer, and Vδ2 cells. After 2 weeks of hydrogen therapy, all six cell subsets increased to within the normal range. The current data indicate that the immunosenescence of advanced non-small cell lung cancer involves nearly all lymphocyte subsets, and 2 weeks of hydrogen treatment can significantly improve most of these indexes. The study was approved by the Ethics Committee of Fuda Cancer Hospital, Jinan University in China (approval No. Fuda20181207) on December 7th, 2018, and was registered on ClinicalTrials.gov (ID: NCT03818347) on January 24th, 2019.

A narrative review of hydrogen oncology: from real world survey to real world evidence.

The use of hydrogen for cancer control has made great progress in cytology and animal experiments. With the increasing number of hydrogen products on the market, larger numbers of advanced cancer patients have participated in clinical trials or received treatment at home after purchase. Our study reported a real-world survey from 82 patients with good cancer control using hydrogen products, including real world evidence from patients who received ineffective traditional treatment, patients who received traditional treatment that failed, or patients who refused traditional treatment. Two typical cases were reported herein. Subsequently, we included studies on the mechanism of hydrogen oncology. The mechanism of cancer control using hydrogen includes the inhibition of tumor cells and the activation of exhausted lymphocytes. Large-scale real world evidence has shown clinical value, and yet remains to be further developed and researched.

Irreversible electroporation plus allogenic Vγ9Vδ2 T cells enhances antitumor effect for locally advanced pancreatic cancer patients.

Immunotherapy has limited efficacy against locally advanced pancreatic cancer (LAPC) due to the presence of an immunosuppressive microenvironment (ISM). Irreversible electroporation (IRE) can not only induce immunogenic cell death, but also alleviate immunosuppression. This study aimed to investigate the antitumor efficacy of IRE plus allogeneic γδ T cells in LAPC patients. A total of 62 patients who met the eligibility criteria were enrolled in this trial, then randomized into two groups (A: n = 30 and B: n = 32). All patients received IRE therapy and after receiving IRE, the group A patients received at least two cycles of γδ T-cell infusion as one course continuously. Group A patients had better survival than group B patients (median OS: 14.5 months vs. 11 months; median PFS: 11 months vs. 8.5 months). Moreover, the group A patients treated with multiple courses of γδ T-cell infusion had longer OS (17 months) than those who received a single course (13.5 months). IRE combined with allogeneic γδ T-cell infusion is a promising strategy to enhance the antitumor efficacy in LAPC patients, yielding extended survival benefits.ClinicalTrials.gov ID: NCT03180437.

Hydrogen therapy can be used to control tumor progression and alleviate the adverse events of medications in patients with advanced non-small cell lung cancer.

Chemotherapy, targeted therapy, and immunotherapy are used against advanced non-small cell lung cancer. A clinically efficacious method for relieving the adverse events associated of such therapies is lacking. Fifty-eight adult patients were enrolled in our trial to relieve pulmonary symptoms or the adverse events of drugs. Twenty patients who refused drug treatment were assigned equally and randomly to a hydrogen (H2)-only group and a control group. According to the results of tumor-gene mutations and drug-sensitivity tests, 10, 18, and 10 patients were enrolled into chemotherapy, targeted therapy, and immunotherapy groups in which these therapies were combined with H2-therapy, respectively. Patients underwent H2 inhalation for 4-5 hours per day for 5 months or stopped when cancer recurrence. Before study initiation, the demographics (except for tumor-mutation genes) and pulmonary symptoms (except for moderate cough) of the five groups showed no significant difference. During the first 5 months of treatment, the prevalence of symptoms of the control group increased gradually, whereas that of the four treatment groups decreased gradually. After 16 months of follow-up, progression-free survival of the control group was lower than that of the H2-only group, and significantly lower than that of H2 + chemotherapy, H2 + targeted therapy, and H2 + immunotherapy groups. In the combined-therapy groups, most drug-associated adverse events decreased gradually or even disappeared. H2 inhalation was first discovered in the clinic that can be used to control tumor progression and alleviate the adverse events of medications for patients with advanced non-small cell lung cancer. This study was approved by the Ethics Committee of Fuda Cancer Hospital of Jinan University on December 7, 2018 (approval No. Fuda20181207), and was registered at ClinicalTrials.gov (Identifier: NCT03818347) on January 28, 2019.