Current trends in gas-synergized phototherapy for improved antitumor theranostics.

Phototherapy, such as photothermal therapy (PTT) and photodynamic therapy (PDT), has been considered an elegant solution to eradicate tumors due to its minimal invasiveness and low systemic toxicity. Nevertheless, it is still challenging for phototherapy to achieve ideal outcomes and clinical translation due to its inherent drawbacks. Owing to the unique biological functions, diverse gases have attracted growing attention in combining with phototherapy to achieve super-additive therapeutic effects. Specifically, gases such as nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S) have been proven to kill tumor cells by inducing mitochondrial damage in synergy with phototherapy. Additionally, several gases not only enhance the thermal damage in PTT and the reactive oxygen species (ROS) production in PDT but also improve the tumor accumulation of photoactive agents. The inflammatory responses triggered by hyperthermia in PTT are also suppressed by the combination of gases. Herein, we comprehensively review the latest studies on gas-synergized phototherapy for cancer therapy, including (1) synergistic mechanisms of combining gases with phototherapy; (2) design of nanoplatforms for gas-synergized phototherapy; (3) multimodal therapy based on gas-synergized phototherapy; (4) imaging-guided gas-synergized phototherapy. Finally, the current challenges and future opportunities of gas-synergized phototherapy for tumor treatment are discussed. STATEMENT OF SIGNIFICANCE: 1. The novelty and significance of the work with respect to the existing literature. (1) Strategies to design nanoplatforms for gas-synergized anti-tumor phototherapy have been summarized for the first time. Meanwhile, the integration of various imaging technologies and therapy modalities which endow these nanoplatforms with advanced theranostic capabilities has been summarized. (2) The mechanisms by which gases synergize with phototherapy to eradicate tumors are innovatively and comprehensively summarized. 2. The scientific impact and interest. This review elaborates current trends in gas-synergized anti-tumor phototherapy, with special emphases on synergistic anti-tumor mechanisms and rational design of therapeutic nanoplatforms to achieve this synergistic therapy. It aims to provide valuable guidance for researchers in this field.

The Advancement of Gas-Generating Nanoplatforms in Biomedical Fields: Current Frontiers and Future Perspectives.

Diverse gases (NO, CO, H2 S, H2 , etc.) have been widely applied in the medical intervention of various diseases, including cancer, cardiovascular disease, ischemia-reperfusion injury, bacterial infection, etc., attributing to their inherent biomedical activities. Although many gases have many biomedical activities, their clinical use is still limited due to the rapid and free diffusion behavior of these gases molecules, which may cause potential side effects and/or ineffective treatment. Gas-generating nanoplatforms (GGNs) are effective strategies to address the aforementioned challenges of gas therapy by preventing gas production or release at nonspecific sites, enhancing GGNs accumulation at targeted sites, and controlling gas release in response to exogenous (UV, NIR, US, etc.) or endogenous (H2 O2 , GSH, pH, etc.) stimuli at the lesion site, further maintaining gas concentration within the effective range and achieving the purpose of disease treatment. This review comprehensively summarizes the advancements of "state-of-the-art" GGNs in the recent three years, with emphasis on the composition, structure, preparation process, and gas release mechanism of the nanocarriers. Furthermore, the therapeutic effects and limitations of GGNs in preclinical studies using cell/animal models are discussed. Overall, this review enlightens the further development of this field and promotes the clinical transformation of gas therapy.

Intelligent Nanomedicine Approaches Using Medical Gas-Mediated Multi-Therapeutic Modalities Against Cancer.

The emerging area of gas-mediated cancer treatment has received widespread attention in the medical community. Featuring unique physical, chemical, and biological properties, nanomaterials can facilitate the delivery and controllable release of medicinal gases at tumor sites, and also serve as ideal platforms for the integration of other therapeutic modalities with gas therapy to augment cancer therapeutic efficacy. This review presents an overview of anti-cancer mechanisms of several therapeutic gases: nitric oxide (NO), hydrogen sulfide (H2S), carbon monoxide (CO), oxygen (O2), and hydrogen (H2). Controlled release behaviors of gases under different endogenous and exogenous stimuli are also briefly discussed, followed by their synergistic effects with different therapeutic modes. Moreover, the potential challenges and future prospects regarding gas therapy based on nanomaterials are also described, aiming to facilitate the advancement of gas therapeutic nanomedicine in new frontiers for highly efficient cancer treatment.

Near-infrared light-triggered nano-prodrug for cancer gas therapy.

Gas therapy (GT) has attracted increasing attention in recent years as a new cancer treatment method with favorable therapeutic efficacy and reduced side effects. Several gas molecules, such as nitric oxide (NO), carbon monoxide (CO), hydrogen (H2), hydrogen sulfide (H2S) and sulfur dioxide (SO2), have been employed to treat cancers by directly killing tumor cells, enhancing drug accumulation in tumors or sensitizing tumor cells to chemotherapy, photodynamic therapy or radiotherapy. Despite the great progress of gas therapy, most gas molecules are prone to nonspecific distribution when administered systemically, resulting in strong toxicity to normal tissues. Therefore, how to deliver and release gas molecules to targeted tissues on demand is the main issue to be considered before clinical applications of gas therapy. As a specific and noninvasive stimulus with deep penetration, near-infrared (NIR) light has been widely used to trigger the cleavage and release of gas from nano-prodrugs via photothermal or photodynamic effects, achieving the on-demand release of gas molecules with high controllability. In this review, we will summarize the recent progress in cancer gas therapy triggered by NIR light. Furthermore, the prospects and challenges in this field are presented, with the hope for ongoing development.

Recent progress in nanomedicine for enhanced cancer chemotherapy.

As one of the most important cancer treatment strategies, conventional chemotherapy has substantial side effects and leads easily to cancer treatment failure. Therefore, exploring and developing more efficient methods to enhance cancer chemotherapy is an urgently important problem that must be solved. With the development of nanotechnology, nanomedicine has showed a good application prospect in improving cancer chemotherapy. In this review, we aim to present a discussion on the significant research progress in nanomedicine for enhanced cancer chemotherapy. First, increased enrichment of drugs in tumor tissues relying on different targeting ligands and promoting tissue penetration are summarized. Second, specific subcellular organelle-targeted chemotherapy is discussed. Next, different combinational strategies to reverse multidrug resistance (MDR) and improve the effective intracellular concentration of therapeutics are discussed. Furthermore, the advantages of combination therapy for cancer treatment are emphasized. Finally, we discuss the major problems facing therapeutic nanomedicine for cancer chemotherapy, and propose possible future directions in this field.

A continuous stimuli-responsive system for NIR-II fluorescence/photoacoustic imaging guided photothermal/gas synergistic therapy.

Nanosystems responsive to a tumor microenvironment (TME) have recently attracted great attention due to their potential in precision cancer theranostics. However, theranostic nanosystems with a TME-activated consecutive cascade for the accurate diagnosis and treatment of cancer have rarely been exploited. Herein, an activatable theranostic nanosystem (Bi2S3-Ag2S-DATS@BSA-N3 NYs) is designed and constructed on the basis of a one-pot biomineralization method and surface functional modification to improve second near-infrared (NIR-II) fluorescence/photoacoustic (PA) imaging-guided photothermal therapy (PTT)/gas therapy (GT). Based on enhanced penetration and retention (EPR) effect-mediated tumor accumulation, the tumor-overexpressed glutathione (GSH) can accelerate hydrogen sulfide (H2S) generation from the nanoparticles by reacting with the encapsulated diallyl trisulfide (DATS). Meanwhile, the in situ released H2S can be used not only for gas therapy, but also to start the reduction of -N3(-) to -NH2(+), thereby enhancing the tumor-specific aggregation of NYs. As a result, the activatable nanosystems with excellent tumor accumulation and biodistribution could achieve an accurate NIR-II/PA dual-modality imaging for guiding the synergistic anticancer efficacy (PTT/GT). Thus, this work provides a promising TME-mediated continuously responsive strategy for efficient anticancer therapy.

Hydrogen gas (XEN) inhalation ameliorates airway inflammation in asthma and COPD patients.

BACKGROUND: Hydrogen was proven to have anti-oxidative and anti-inflammation effects to various diseases. AIM: We wish to investigate the acute effects of inhaled hydrogen on airway inflammation in patients with asthma and chronic obstructive pulmonary disease (COPD). DESIGN: Prospective study. METHODS: In total, 2.4% hydrogen containing steam mixed gas (XEN) was inhaled once for 45 min in 10 patients with asthma and 10 patients with COPD. The levels of granulocyte-macrophage colony stimulating factor, interferon-γ, interleukin-1ß (IL-1ß), IL-2, IL-4, IL-6 and so on in peripheral blood and exhaled breath condensate (EBC) before and after 'XEN' inhalation were measured. RESULTS: 45 minutes 'XEN' inhalation once decreased monocyte chemotactic protein 1 level in both COPD (564.70-451.51 pg/mL, P = 0.019) and asthma (386.39-332.76 pg/mL, P = 0.033) group, while decreased IL-8 level only in asthma group (5.25-4.49 pg/mL, P = 0.023). The level of EBC soluble cluster of differentiation-40 ligand in COPD group increased after inhalation (1.07-1.16 pg/mL, P = 0.031), while IL-4 and IL-6 levels in EBC were significantly lower after inhalation in the COPD (0.80-0.64 pg/mL, P = 0.025) and asthma (0.06-0.05 pg/mL, P = 0.007) group, respectively. CONCLUSIONS: A single inhalation of hydrogen for 45 min attenuated inflammatory status in airways in patients with asthma and COPD.

Organ preservation solution containing dissolved hydrogen gas from a hydrogen-absorbing alloy canister improves function of transplanted ischemic kidneys in miniature pigs.

Various methods have been devised to dissolve hydrogen gas in organ preservation solutions, including use of a hydrogen gas cylinder, electrolysis, or a hydrogen-generating agent. However, these methods require considerable time and effort for preparation. We investigated a practical technique for rapidly dissolving hydrogen gas in organ preservation solutions by using a canister containing hydrogen-absorbing alloy. The efficacy of hydrogen-containing organ preservation solution created by this method was tested in a miniature pig model of kidney transplantation from donors with circulatory arrest. The time required for dissolution of hydrogen gas was only 2-3 minutes. When hydrogen gas was infused into a bag containing cold ETK organ preservation solution at a pressure of 0.06 MPa and the bag was subsequently opened to the air, the dissolved hydrogen concentration remained at 1.0 mg/L or more for 4 hours. After warm ischemic injury was induced by circulatory arrest for 30 minutes, donor kidneys were harvested and perfused for 5 minutes with hydrogen-containing cold ETK solution or hydrogen-free cold ETK solution. The perfusion rate was faster from the initial stage with hydrogen-containing cold ETK solution than with hydrogen-free ETK solution. After storage of the kidney in hydrogen-free preservation solution for 1 hour before transplantation, no urine production was observed and blood flow was not detected in the transplanted kidney at sacrifice on postoperative day 6. In contrast, after storage in hydrogen-containing preservation solution for either 1 or 4 hours, urine was detected in the bladder and blood flow was confirmed in the transplanted kidney. This method of dissolving hydrogen gas in organ preservation solution is a practical technique for potentially converting damaged organs to transplantable organs that can be used safely in any clinical setting where organs are removed from donors.

Gas-Mediated Cancer Bioimaging and Therapy.

Gas-involving cancer theranostics have attracted considerable attention in recent years due to their high therapeutic efficacy and biosafety. We have reviewed the recent significant advances in the development of stimuli-responsive gas releasing molecules (GRMs) and gas nanogenerators for cancer bioimaging, targeted and controlled gas therapy, and gas-sensitized synergistic therapy. We have focused on gases with known anticancer effects, such as oxygen (O2), carbon monoxide (CO), nitric oxide (NO), hydrogen sulfide (H2S), hydrogen (H2), sulfur dioxide (SO2), carbon dioxide (CO2), and heavy gases that act via the gas-generating process. The GRMs and gas nanogenerators for each gas have been described in terms of the stimulation method, followed by their applications in ultrasound and multimodal imaging, and finally their primary and synergistic actions with other cancer therapeutic modalities. The current challenges and future possibilities of gas therapy and imaging vis-à-vis clinical translation have also been discussed.

Aplicación del ozono interescalénico en la radiculopatía cervical por hernia discal / Application of intercalenic ozone in cervical radiculopathy due to herniated disc

Introducción: el ozono es un gas médico descrito desde el siglo XIX que ha tenido su evolución hasta a la fecha en cuanto a sus aplicaciones y su utilidad en diversas enfermedades por su actuación a nivel molecular y en disímiles enfermedades asociadas a procesos dolorosos de origen inflamatorio como los presentes en las hernia discales de la columna vertebral. Método: estudio retrospectivo con 20 pacientes atendidos en la consulta externa de Neurocirugía del Hospital Miguel Enríquez desde de Diciembre 2016 hasta Abril 2017 con el diagnostico de una radiculopatía cervical por hernia discal. Se le aplicó 10 ML de ozono con una concentración 22 mg/litro tres veces en la semana durante 10 semanas solamente se utilizó este tipo de terapia; obteniendo mejoría en 15 pacientes. Resultados: predominando los mayores de 51 años para un 50 por ciento, en nuestra serie predominó el sexo femenino para un 80 por ciento. En cuanto al cuadro clínico prevaleció la disminución de la fuerza muscular para un 60 por ciento en 12 pacientes, seguidos del dolor cervical y el interescapular para un 75 por ciento y 55 por ciento respectivamente. Se halló mejoría en 15 pacientes para un 75 por ciento y en los otros 5, en tres pacientes no continuaron el tratamiento y en dos no se obtuvo mejoría. Conclusiones: tenemos otra alternativa en la aplicación del ozono por el espacio interescalénico como tratamiento analgésicos y antiinflamatorio en las radiculopatía por hernia discales cervicales(AU)

Introduction: Ozone is a medical gas described since the nineteenth century that has had its evolution up to date in terms of its applications and its usefulness in various diseases for its performance at the molecular level and dissimilar diseases associated with painful processes of inflammatory origin such as those present in herniated discs of the spine. Method: Retrospective study with 20 patients assisted in the outpatient consultation of the Miguel Enríquez Hospital from December 2016 to April 2017 with the diagnosis of a cervical radiculopathy by herniated disc. 10 ML of ozone applied with a concentration of 22 mg/liter three times in the week for 10 weeks only this type of therapy used getting improvement in 15 patients. Results: predominating the older than 51 years for 50 percent, in our series predominated the female sex for 80 percent .As for the clinical picture, decreased muscle strength was prevailed for 60 percent in 12 patients, followed by cervical pain and interescapular for 75 percent and 55 percent respectively. We found improvement in 15 patients for 75 percent and in the other 5, in 3 patients did not continue the treatment and in two, no improvement obtained. Conclusions: We have another alternative in the application of ozone by the intercalenic space as analgesic and anti-inflammatory treatment in cervical herniated discus radiculopathy(AU)

The role of medical gas in stroke: an updated review.

Medical gas is a large class of bioactive gases used in clinical medicine and basic scientific research. At present, the role of medical gas in neuroprotection has received growing attention. Stroke is a leading cause of death and disability in adults worldwide, but current treatment is still very limited. The common pathological changes of these two types of stroke may include excitotoxicity, free radical release, inflammation, cell death, mitochondrial disorder, and blood-brain barrier disruption. In this review, we will discuss the pathological mechanisms of stroke and the role of two medical gases (hydrogen and hydrogen sulfide) in stroke, which may potentially provide a new insight into the treatment of stroke.

Hydrogen gas improves left ventricular hypertrophy in Dahl rat of salt-sensitive hypertension.

PURPOSE: Hypertension is an important risk factor for death resulting from stroke, myocardial infarction, and end-stage renal failure. Hydrogen (H2) gas protects against many diseases, including ischemia-reperfusion injury and stroke. The effects of H2 on hypertension and its related left ventricular (LV) function have not been fully elucidated. The purpose of this study was to investigate the effects of H2 gas on hypertension and LV hypertrophy using echocardiography. METHODS: Dahl salt-sensitive (DS) rats were randomly divided into three groups: those fed an 8% NaCl diet until 12 weeks of age (8% NaCl group), those additionally treated with 2% H2 gas (8% NaCl + 2% H2 group), and control rats maintained on a diet containing 0.3% NaCl until 12 weeks of age (0.3% NaCl group). H2 gas was supplied through a gas flowmeter and delivered by room air (2% hydrogenated room air, flow rate of 10 L/min) into a cage surrounded by an acrylic chamber. We evaluated interventricular septal wall thickness (IVST), LV posterior wall thickness (LVPWT), and LV mass using echocardiography. RESULTS: IVST, LVPWT, and LV mass were significantly higher in the 8% NaCl group than the 0.3% NaCl group at 12 weeks of age, whereas they were significantly lower in the 8% NaCl + 2% H2 group than the 8% NaCl group. There was no significant difference in systolic blood pressure between the two groups. CONCLUSION: Our findings suggest that chronic H2 gas inhalation may help prevent LV hypertrophy in hypertensive DS rats.

Gas-Generating Nanoplatforms: Material Chemistry, Multifunctionality, and Gas Therapy.

The fast advances of theranostic nanomedicine enable the rational design and construction of diverse functional nanoplatforms for versatile biomedical applications, among which gas-generating nanoplatforms (GGNs) have emerged very recently as unique theranostic nanoplatforms for broad gas therapies. Here, the recent developments of the rational design and chemical construction of versatile GGNs for efficient gas therapies by either exogenous physical triggers or endogenous disease-environment responsiveness are reviewed. These gases involve some therapeutic gases that can directly change disease status, such as oxygen (O2 ), nitric oxide (NO), carbon monoxide (CO), hydrogen (H2 ), hydrogen sulfide (H2 S) and sulfur dioxide (SO2 ), and other gases such as carbon dioxide (CO2 ), dl-menthol (DLM), and gaseous perfluorocarbon (PFC) for supplementary assistance of the theranostic process. Abundant nanocarriers have been adopted for gas delivery into lesions, including poly(d,l-lactic-co-glycolic acid), micelles, silica/mesoporous silica, organosilica, MnO2 , graphene, Bi2 Se3 , upconversion nanoparticles, CaCO3 , etc. Especially, these GGNs have been successfully developed for versatile biomedical applications, including diagnostic imaging and therapeutic use. The biosafety issue, challenges faced, and future developments on the rational construction of GGNs are also discussed for further promotion of their clinical translation to benefit patients.

Mussel-inspired catalytic selenocystamine-dopamine coatings for long-term generation of therapeutic gas on cardiovascular stents.

The development of a nitric oxide (NO)-generating surface with long-term, stable and controllable NO release improves the therapeutic efficacy of cardiovascular stents. In this work, we developed a "one-pot" method inspired by mussel adhesive proteins for copolymerization of selenocystamine (SeCA) and dopamine (Dopa) to form a NO-generating coating on a 316 L stainless steel (SS) stent. This "one-pot" method is environmentally friendly and easy to popularize, with many advantages including simple manufacturing procedure, high stability and no involvement of organic solvents. Such SeCA/Dopa coatings also enabled us to develop a catalytic surface for local NO-generation by reaction of endogenously existing S-nitrothiol species from fresh blood. We found that the developed SeCA/Dopa coatings could release NO in a controllable and stable manner for more than 60 days. Additionally, the released NO significantly inhibited smooth muscle cell (SMC) proliferation and migration, as well as platelet activation and aggregation through the up-regulation of cyclic guanosine monophosphate synthesis. Moreover, such NO generation enhanced the adhesion, proliferation and migration of endothelial cells (ECs), and achieved rapid in vivo re-endothelialization, effectively reducing in-stent restenosis and neointimal hyperplasia. We envision that the SeCA/Dopa-coated 316 L SS stent could be a promising platform for treatment of cardiovascular diseases.

A 50-50% mixture of nitrous oxide-oxygen in transrectal ultrasound-guided prostate biopsy: A randomized and prospective clinical trial.

INTRODUCTION: Transrectal ultrasound-guided biopsy (TUSPB) is the standard method of diagnosis for prostate cancer, and although it is well tolerated by some patients, it presents a discomfort rate of 65 to 90%, which may be associated with pain. For convenience, it is agreed that a method of analgesia and sedation is necessary. For this purpose, this study aimed to evaluate the impact of inhalation of a 50-50% N2O-O2 gas mixture on pain intensity in these patients. MATERIAL AND METHODS: Randomized, double-blinded clinical trial, conducted at Antônio Pedro University Hospital (Hospital Universitário Antônio Pedro), Niterói, RJ, Brazil, containing two groups of 42 patients: a control (C) group, which received 100% oxygen inhalation, and a nitrous oxide (NO) group, which received inhalation of the 50-50% N2O-O2 mixture, self-administered during TUSPB. The pain intensity and degree of satisfaction were evaluated through a visual analogue scale (VAS), as was the frequency of adverse events. RESULTS: Eighty-four patients were included in the study, with 42 in each group. The mean pain intensity was lower in the NO group than in the C group [2.52 (0-10) vs 5.95 (0-10), p < 0.001], and the degree of satisfaction was higher in the NO group than in the C group (8.14 vs. 4.69, p < 0.001). The adverse effects were somnolence, dizziness, nausea, vomiting, discomfort and euphoria without differences between the groups. CONCLUSION: The 50-50% N2O-O2 mixture was effective in reducing pain intensity and increasing the degree of satisfaction in TUSPB, with tolerable side effects.

Precision gas therapy using intelligent nanomedicine.

Gas therapy is an emerging and promising field, utilizing the unique therapeutic effects of several kinds of gases (NO, CO, H2S and H2) towards many major diseases, including cancer and cardiovascular diseases, and it is also facing challenges relating to enhancing gas therapy efficacy and avoiding gas poisoning risks. Here, we have proposed a new concept for precision gas therapy using a nanomedicine strategy to overcome the challenges. In this perspective, we have addressed a series of existing and potential solutions from the point of view of nanomedicine, and conveyed a collection of opinions about future expandable research into precision gas therapy.

Efficacy of Vitrectomy Combined with Subretinal rtPA Injection with Gas or Air Tamponade.

Background Functional and anatomical outcome after vitrectomy with rtPA combined with gas or air tamponade. Patients and methods Retrospective analysis of pseudophakic patients treated with subretinal rtPA and gas or air tamponade. The primary endpoint was displacement of haemorrhage six months after surgery. The secondary endpoints were visual acuity (BCVA), haemorrhage diameter (MHD) and central macular thickness (CMT), as measured by SD-OCT. Results 53 of 85 eyes were pseudophakic. 27 of these eyes were treated with air tamponade and 26 with gas tamponade. For patients with air tamponade, the mean BCVA improved from 20/530 to 20/355 (p = 0.01). MHD and CMT decreased from 6386 ± 2281 µm to 3805 ± 2397 µm (p < 0.001) and 895 ± 592 µm to 532 ± 386 µm (p < 0.001), respectively. For patients with gas tamponade, the mean BCVA improved only slightly, from 20/471 to 20/394 (p = 0.17). MHD and CMT exhibited statistically significant decreases from 6759 ± 1773 µm to 3525 ± 1548 µm (p < 0.001) and 1089 ± 587 µm to 537 ± 251 µm (p < 0.001), respectively. Conclusions Vitrectomy with subretinal rtPA injection has strong functional and anatomical effects on submacular haemorrhages with both gas and air tamponade.

Modified carbodissection: A new technique for harvesting the internal mammary artery.

The modified carbodissection technique is a new technique for harvesting the internal mammary artery during coronary artery bypass graft surgery. It is performed using an improvised instrument that consists of an electrocautery device and a carbon dioxide blower/mister. It combines electrocautery dissection and continuous controlled gas blow dissection along with saline irrigation mist. Gas dissection causes vasodilation and maintains the artery in a dilated state during dissection. Saline flow reduces the amount of heat generated at the cautery site and prevents drying and desiccation of the tissues. This technique is safe in terms of reduced thermal injury, and reduced early arterial spasm and myocardial ischemia, and it improves vision during harvest and shortens the duration of the harvesting procedure.

Microwave-activated nanodroplet vaporization for highly efficient tumor ablation with real-time monitoring performance.

The fast development of nanotechnology has provided a new efficient strategy for enhancing the therapeutic efficiency of various treatment modalities against cancer. However, the improvement of minimally invasive microwave therapy based on nanomaterials has not been realized. In this work, we successfully designed and synthesized a novel folate-targeted nanodroplet (TPN) with a composite mixture of perfluorocarbons as the core and lipid as the shell, which exerts the distinctive dual functions as the adjuvant for highly efficient percutaneous ultrasound imaging-guided microwave ablation (MWA) of tumors. Based on the unique phase-changeable performance of TPN nanosystem, a novel microwave-droplet vaporization (MWDV) strategy was proposed, for the first time, to overcome the critical issues of traditional acoustic-droplet vaporization (ADV) and optical-droplet vaporization (ODV) for cancer theranostics. Especially, the elaborately designed TPN can overcome the challenges of indistinct imaging of ablation margin and the limited ablation zone of MWA modality against cancer. The high efficiency of this new MWDV strategy has been systematically elucidated in vitro, ex vivo and in vivo. Therefore, such a successful demonstration of the role of nanomaterials (TPN in this case) in ultrasound imaging-guided MWA therapy against cancer provides a highly feasible strategy to effectively enhance the MWA outcome with the specific features of high efficiency and biosafety.

Ozone Gas Bath Combined with Endovenous Laser Therapy for Lower Limb Venous Ulcers: A Randomized Clinical Trial.

BACKGROUND: Endovenous laser therapy (EVLT) is safe and effective for lower limb venous ulcers. However, severe necrosis and infection in the ulcer area are contraindications of puncture and EVLT. Local bath with ozone gas has been shown to improve the condition of ulcer areas. The aim of this study was to evaluate the clinical efficacy of ozone gas bath combined with EVLT in comparison with EVLT alone for the treatment for lower limb venous ulcers. PATIENTS AND METHODS: Ninety-two patients with venous ulcers were randomized to receive ozone gas bath combined with EVLT (OEVLT group) or EVLT alone (EVLT group). In the OEVLT group, the venous ulcers were preconditioned with ozone gas bath prior to EVLT. The minimum follow-up time was 12 months. The two groups were compared in terms of complete occlusion of the treated veins, ulcer healing ratio, ratio of ulcer recurrence, patient satisfaction, complications, and side effects. RESULTS: There was no significant difference in venous occlusion between the two groups. The ratio of ulcer healing in the OEVLT group was significantly higher than the EVLT group at 12 months follow-up. Patients in the OEVLT group showed better satisfaction and a lower recurrence ratio than the OEVLT group. No severe complications or side effects occurred in either groups. CONCLUSIONS: Ozone gas bath combined with EVLT showed improved efficacy for the treatment of lower limb venous ulcers and lower recurrence ratio comparison with EVLT alone. This procedure is a safe and technically feasible.