Nanoarchitectonic Engineering of Thermal-Responsive Magnetic Nanorobot Collectives for Intracranial Aneurysm Therapy.

Stent-assisted coiling is a main treatment modality for intracranial aneurysms (IAs) in clinics, but critical challenges remain to be overcome, such as exogenous implant-induced stenosis and reliance on antiplatelet agents. Herein, an endovascular approach is reported for IA therapy without stent grafting or microcatheter shaping, enabled by active delivery of thrombin (Th) to target aneurysms using innovative phase-change material (PCM)-coated magnetite-thrombin (Fe3O4-Th@PCM) FTP nanorobots. The nanorobots are controlled by an integrated actuation system of dynamic torque-force hybrid magnetic fields. With robust intravascular navigation guided by real-time ultrasound imaging, nanorobotic collectives can effectively accumulate and retain in model aneurysms constructed in vivo, followed by controlled release of the encapsulated Th for rapid occlusion of the aneurysm upon melting the protective PCM (thermally responsive in a tunable manner) through focused magnetic hyperthermia. Complete and stable aneurysm embolization is confirmed by postoperative examination and 2-week postembolization follow-up using digital subtraction angiography (DSA), contrast-enhanced ultrasound (CEUS), and histological analysis. The safety of the embolization therapy is assessed through biocompatibility evaluation and histopathology assays. This strategy, seamlessly integrating secure drug packaging, agile magnetic actuation, and clinical interventional imaging, avoids possible exogenous implant rejection, circumvents cumbersome microcatheter shaping, and offers a promising option for IA therapy.

Magnetically actuated sonodynamic nanorobot collectives for potentiated ovarian cancer therapy.

Ovarian cancer presents a substantial challenge due to its high mortality and recurrence rates among gynecological tumors. Existing clinical chemotherapy treatments are notably limited by drug resistance and systemic toxic side effects caused by off target drugs. Sonodynamic therapy (SDT) has emerged as a promising approach in cancer treatment, motivating researchers to explore synergistic combinations with other therapies for enhanced efficacy. In this study, we developed magnetic sonodynamic nanorobot (Fe3O4@SiO2-Ce6, FSC) by applying a SiO2 coating onto Fe3O4 nanoparticle, followed by coupling with the sonosensitizer Ce6. The magnetic FSC nanorobot collectives could gather at fixed point and actively move to target site regulated by magnetic field. In vitro experiments revealed that the magnetic FSC nanorobot collectives enabled directional navigation to the tumor cell area under guidance. Furthermore, under low-intensity ultrasonic stimulation, FSC nanorobot collectives mediated sonodynamic therapy exhibited remarkable anti-tumor performance. These findings suggest that magnetically actuated sonodynamic nanorobot collectives hold promising potential for application in target cancer therapy.

Lactic acid responsive sequential production of hydrogen peroxide and consumption of glutathione for enhanced ferroptosis tumor therapy.

Ferroptosis is characterized by the lethal accumulation of lipid reactive oxygen species (ROS), which has great potential for tumor therapy. However, developing new ferroptosis-inducing strategies by combining nanomaterials with small molecule inducers is important. In this study, an enzyme-gated biodegradable natural-product delivery system based on lactate oxidase (LOD)-gated biodegradable iridium (Ir)-doped hollow mesoporous organosilica nanoparticles (HMONs) loaded with honokiol (HNK) (HNK@Ir-HMONs-LOD, HIHL) is designed to enhance ferroptosis in colon tumor therapy. After reaching the tumor microenvironment, the outer LOD dissociates and releases the HNK to induce ferroptosis. Moreover, the released dopant Ir4+ and disulfide-bridged organosilica frameworks deplete intracellular glutathione (GSH), which is followed by GSH-mediated Ir(IV)/Ir(III) conversion. This leads to the repression of glutathione peroxidase 4 (GPX4) activity and decomposition of intratumoral hydrogen peroxide (H2O2) into hydroxyl radicals (•OH) by Ir3+-mediated Fenton-like reactions. Moreover, LOD efficiently depletes lactic acid to facilitate the generation of H2O2 and boost the Fenton reaction, which in turn enhances ROS generation. With the synergistic effects of these cascade reactions and the release of HNK, notable ferroptosis efficacy was observed both in vitro and in vivo. This combination of natural product-induced and lactic acid-responsive sequential production of H2O2 as well as the consumption of glutathione may provide a new paradigm for achieving effective ferroptosis-based cancer therapy.

Dual-Functional Laser-Guided Magnetic Nanorobot Collectives against Gravity for On-Demand Thermo-Chemotherapy of Peritoneal Metastasis.

Combining hyperthermic intraperitoneal chemotherapy with cytoreductive surgery is the main treatment modality for peritoneal metastatic (PM) carcinoma despite the off-target effects of chemotherapy drugs and the ineluctable side effects of total abdominal heating. Herein, a laser-integrated magnetic actuation system that actively delivers doxorubicin (DOX)-grafted magnetic nanorobot collectives to the tumor site in model mice for local hyperthermia and chemotherapy is reported. With intraluminal movements controlled by a torque-force hybrid magnetic field, these magnetic nanorobots gather at a fixed point coinciding with the position of the localization laser, moving upward against gravity over a long distance and targeting tumor sites under ultrasound imaging guidance. Because aggregation enhances the photothermal effect, controlled local DOX release is achieved under near-infrared laser irradiation. The targeted on-demand photothermal therapy of multiple PM carcinomas while minimizing off-target tissue damage is demonstrated. Additionally, a localization/treatment dual-functional laser-integrated magnetic actuation system is developed and validated in vivo, offering a potentially clinically feasible drug delivery strategy for targeting PM and other intraluminal tumors.

Acidity-Biodegradable Iridium-Coordinated Nanosheets for Amplified Ferroptotic Cell Death Through Multiple Regulatory Pathways.

Ferroptosis-based treatment strategies display the potential to suppress some malignant tumors with intrinsic apoptosis resistance. However, current related cancer treatments are still hampered by insufficient intracellular reactive oxygen species (ROS) levels and Fe2+ contents, posing considerable challenges for their clinical translation. Herein, an intracellular acid-biodegradable iridium-coordinated nanosheets (Ir-Hemin) with sonodynamic therapy (SDT) properties to effectively induce ferroptosis in tumor cells through multiple regulatory pathways are proposed. Under ultrasound (US) irradiation, Ir-Hemin nanosheets act as nanosonosensitizers to effectively generate ROS, subsequently causing the accumulation of lipid peroxides (LPO) and inducing ferroptotic cell death. Furthermore, these Ir-Hemin nanosheets decompose quickly to release hemin and Ir(IV), which deplete intracellular glutathione (GSH) to deactivate the enzyme glutathione peroxidase 4 (GPX4) and initiate the ferroptosis pathway. Specifically, the released hemin enables heme oxygenase 1 (HO-1) upregulation for endogenous ferrous ion supplementation, which compensates for the toxicity concerns brought about by the large uptake of exogenous iron. Surprisingly, Ir-Hemin nanosheets exhibit high tumor accumulation and trigger effective ferroptosis for tumor therapy. These Ir-Hemin nanosheets display pronounced synergistic anticancer efficacy under US stimulation both in vitro and in vivo, providing a strong rationale for the application of ferroptosis in cancer treatment.

Bioactive Iridium Nanoclusters with Glutathione Depletion Ability for Enhanced Sonodynamic-Triggered Ferroptosis-Like Cancer Cell Death.

Ferroptosis is a regulated form of necrotic cell death that involves the accumulation of lipid peroxide (LPO) species in an iron- and reactive oxygen species (ROS)-dependent manner. Previous investigations have reported that ferroptosis-based cancer therapy can overcome the limitations of traditional therapeutics targeting the apoptosis pathway. However, it is still challenging to enhance the antitumor efficacy of ferroptosis due to intrinsic cellular regulation. In this study, a ferroptosis-inducing agent, i.e., chlorin e6 (Ce6)-conjugated human serum albumin-iridium oxide (HSA-Ce6-IrO2 , HCIr) nanoclusters, is developed to achieve sonodynamic therapy (SDT)-triggered ferroptosis-like cancer cell death. The sonosensitizing role of both Ce6 and IrO2 within the HCIr nanoclusters exhibits highly efficient 1 O2 generation capacity upon ultrasound stimulation, which promotes the accumulation of LPO and subsequently induces ferroptosis. Meanwhile, the HCIr can deplete glutathione (GSH) by accelerating Ir (IV)-Ir (III) transition, which further suppresses the activity of glutathione peroxidase 4 (GPX4) to enhance the ferroptosis efficacy. Through in vitro and in vivo experiments, it is demonstrated that HCIr possesses tremendous capacity to reduce the intracellular GSH content, which enhances SDT-triggered ferroptosis-like cancer cell death. Thus, an iridium-nanoclusters-based ferroptosis-inducing agent is developed, providing a promising strategy for inducing ferroptosis-like cancer cell death.

Synergistic Integration and Pharmacomechanical Function of Enzyme-Magnetite Nanoparticle Swarms for Low-Dose Fast Thrombolysis.

Magnetic micro-/nanoparticles are extensively explored over the past decade as active diagnostic/therapeutic agents for minimally invasive medicine. However, sufficient function integration on these miniaturized bodies toward practical applications remains challenging. This work proposes a synergistic strategy via integrating particle functionalization and bioinspired swarming, demonstrated by recombinant tissue plasminogen activator modified magnetite nanoparticles (rtPA-Fe3 O4 NPs) for fast thrombolysis in vivo with low drug dosage. The synthesized rtPA-Fe3 O4 NPs exhibit superior magnetic performance, high biocompatibility, and thrombolytic enzyme activity. Benefiting from a customized magnetic operation system designed for animal experiments and preclinical development, these agglomeration-free NPs can assemble into micro-/milli-scale swarms capable of robust maneuver and reconfigurable transformation for on-demand tasks in complex biofluids. Specifically, the spinning mode of the swarm exerts focused fluid shear stresses while rubbing on the thrombus surface, constituting a mechanical force for clot breakdown. The synergy of the NPs' inherent enzymatic effect and swarming-triggered fluid forces enables amplified efficacy of thrombolysis in an in vivo occlusion model of rabbit carotid artery, using lower drug concentration than clinical dosage. Furthermore, swarming-enhanced ultrasound signals aid in imaging-guided treatment. Therefore, the pharmacomechanical NP swarms herein represent an injectable thrombolytic tool joining advantages of intravenous drug therapy and robotic intervention.

Failure mode effect and criticality analysis of ultrasound device by classification tracking.

BACKGROUND: Medical ultrasound device has been more and more widely used in the hospital and Its safety risk is significantly increased when failures occur. However, there is a lack of quantitative risk assessments of different types of failure modes for medical ultrasound device. This study utilizes a failure mode, effect and criticality analysis (FMECA) approach for quantitative risk evaluation of different failure modes for ultrasound devices. METHODS: The 4216 medical ultrasound device failure records at various hospitals were investigated. A failure mode and effect analysis method was developed for the quantitative evaluation of the risks of different failure modes. Visual correlation analysis was conducted for all categories to identify the causes of various failure modes. Based on the severity, occurrence and detectability of the failure causes determined, the risk priority number (RPN) for each failure mode was back-calculated through the obtained tracking diagram. RESULTS: The failure modes of unclear images, unable to power on and dark shadows on an image had the highest RPNs. One failure mode could be caused by various factors, and the failure location was not necessarily related to the cause of the failure. CONCLUSIONS: This quantitative approach more accurately evaluated the risks of different failure modes, and the results of the corresponding analysis of failure modes and causes could support the rapid determination of the causes of failures in clinical practice.

Guiding Drug Through Interrupted Bloodstream for Potentiated Thrombolysis by C-Shaped Magnetic Actuation System In Vivo.

Fast and effective thrombolysis using tissue plasminogen activator (tPA) is limited by the poor delivery efficiency of thrombolytic drugs, which is induced by an interrupted bloodstream and delayed recanalization. Existing magnetic micro/nanodrug-loaded robots used for targeted thrombotic therapy are limited by the complexity of the clinical verification of nanodrugs and the limited space of magnetic actuation systems. Herein, a general drug delivery strategy based on mass transportation theory for thrombolysis is presented, and an open space C-shaped magnetic actuation system with laser location and ultrasound imaging navigation for in vivo evaluation is developed. tPA can be guided through an interrupted bloodstream to the thrombi by the locomotion of magnetic nanoparticle swarms (MNSs), thereby improving the thrombolysis efficacy. Notably, this strategy is able to quickly establish a life channel to achieve time-critical recanalization, which is typically inaccessible using native tPA. Both in vitro and in vivo thrombolysis experiments demonstrate that the thrombus lysis efficacy significantly increases after the application of the MNS under a rotating magnetic field. This study provides an anticipated C-shaped magnetic actuation system for in vivo validation and also presents a clinically feasible drug delivery strategy for targeted thrombolytic therapy with minimal systemic tPA exposure.

Intermittent time-set technique controlling the temperature of magnetic-hyperthermia-ablation for tumor therapy.

Magnetic-hyperthermia-ablation is considered as an effective and minimally invasive technology for tumor therapy. However, inappropriate temperature control could induce an excessively high temperature which brings potential safety problems and limits clinical transformation of this technique. Herein, aiming to control the temperature during magnetic hyperthermia ablation, we develop an intermittent time-set technique for temperature control in magnetic hyperthermia ablation of tumors using a polylactic-co-glycolic acid (PLGA)-Fe3O4 implant. In vitro, the intermittent time is set as follows: tubes are continuously heated for 110 seconds. Then the heating process is paused for 20 seconds, and then the tubes are reheated for 10 seconds, followed by repeating the last two processes. The temperature elevation profile upon magnetic hyperthermia interestingly also demonstrates good controllability despite some differences in time-setting between in vitro and in vivo. The in vivo results show the temperature fluctuates within the range of 6.45 ± 1.34 °C after reaching the target temperature. Furthermore, we observe the deformation of an implant employing three-dimensional (3D) ultrasound to better understand the temperature change. The results show no significant deformation of the implant after being heated. The microscopic images prove that this simple technique can successfully cause tumor regression. This temperature control technique provides great benefits for hyperthermia ablation against tumors, advancing the magnetic hyperthermal ablation technology in clinical translation.

A pH and magnetic dual-response hydrogel for synergistic chemo-magnetic hyperthermia tumor therapy.

To overcome the toxicity of chemotherapy, increasing attention has been paid to local drug delivery systems (DDSs). pH-Sensitive hydrogels have emerged as promising DDS materials in the biomedical field due to their remarkable characteristics. However, the pH environment in tumor varies from person to person, which makes the applicability of systems based on pH challenging. In this study, we developed a contractible hydroxypropyl methyl cellulose (HPMC)/Fe3O4 hydrogel with dual-response pH and magnetic properties aiming to overcome the limitations of pH-sensitive hydrogel drug delivery systems and further increase their efficiency in tumor therapy. The HPMC/Fe3O4 hydrogel could act as a drug delivery system that combines pH-sensitive triggering and magnetic dual-response drug release for synergistic chemo-magnetic hyperthermia therapy. The drug delivery profile of the HPMC/Fe3O4/doxorubicin hydrochloride (DOX) hydrogel was determined in vitro and revealed a remarkable pH-sensitive performance. After synergistic chemo-magnetic hyperthermia treatment, mice with 4T1 breast cancer xenografts recovered without any recurrence or metastasis, demonstrating the synergistic effect of chemotherapy and magnetic hyperthermia therapy. Meanwhile, reduced toxicity and superior anticancer effects were achieved due to the combined effect of the pH and magnetic hyperthermia response properties. This study demonstrated the high efficacy and low toxicity of the improved design of HPMC/Fe3O4 for drug delivery, which may provide a promising approach for the application of chemo-magnetic hyperthermia cancer therapy.

[Satisfaction Evaluation and Ten Years Practical Application of the After-sale Service of Medical Equipment].

In terms of service management in the medical equipment field, Medical Equipment after-sale Service Satisfaction Evaluation System is established through expert consultation and sample experiment. Meanwhile, questionnaire survey has been applied to local service satisfaction survey work among equipment managements and clinical departments in seventy second and third grade hospitals in Shanghai in ten consecutive years. The result indicates that the satisfaction index has been growing slightly and stably, which clearly demonstrates that the evaluation has continually boosted the service work of various mainstream suppliers. And overall, the evaluation has played an active role in safeguarding and motivating the safety and effectiveness of medical equipment.

[Analysis and Control of Endoscopic Security Risk in Digital Integrated Environment].

Taking Endoscopy in hospitals as the research object, study on the safety risk characteristics in digital integration environment. On the basis of risk analysis, risk prevention and control measures are proposed from personnel, equipment, water and electricity, disinfection and the surrounding environment. Establish the endoscope safety risk management safeguard system to improve the safety risk management level of endoscopy.

[Design and application of regional PACS based on centralized storage model].

Through integration of medical imaging resources of 12 community hospitals in the region, a community hospital diagnostic image center was established in 6th hospital. This paper describes the design of the structure and mode of data storage of regional PACS system and the establishment of a database of medical imaging, through which the medical imaging diagnostic level in the community was improved significantly. Through the application of regional PACS system, medical resource was saved and patient treatment facilitated.

[The development of MR k-space technique research].

This article briefly summarized conventional k-space technique, partial k-space sampling and key hole technique, then introduced the latest applications during these years.

[Calculation of MR radiofrequency specific energy absorption rate and clinical application].

This paper reviews the basic principles and calculation methods of MR specific absorption rate, discusses the clinical application of MR specific absorption rate.

[Quantitative comparison study on the SNR method of phased-array coil in 3.0 T MRI].

In this paper, ACR single image method and NEMA dual-image method were measured SNR using two types of phased-array coils. The correlation equation of the two methods was obtained and substitutability of two methods was analyzed. The results showed that the two methods are replaceable in the evaluation of coils, but the later method gets higher SNR than the first method because structure noise is eliminated.

[Comparative analysis of calculation methods of coil sensitivity in parallel MRI].

Calculation methods of coil sensitivity in parallel MRI were elaborated, compared and analyzed.

[Application of wireless sensor networks in healthcare].

This paper introduces general architecture of wireless sensor networks architecture and application in healthcare, discusses the application direction which is urgent need to expand in medical field.

[Establishment and application of DR automatic system based on DICOM3.0 BPE].

This paper introduces a new application of PACS in our hospital. Through the integration of PACS, HIS and RIS, digital transformation is made in every step. The functional modules of Body Parts Examined in DICOM is set and good link between PACS and DR is made. So the equipment can retrieval the inspection area automatically and make adjustment on the parameters correspondingly. It makes the workflow optimized and improves the efficiency greatly.