Role of the Voltage-Gated Proton Channel Hv1 in Nervous Systems / 神经科学通报·英文版

Hv1 is the only voltage-gated proton-selective channel in mammalian cells. It contains a conserved voltage-sensor domain, shared by a large class of voltage-gated ion channels, but lacks a pore domain. Its primary role is to extrude protons from the cytoplasm upon pH reduction and membrane depolarization. The best-known function of Hv1 is the regulation of cytosolic pH and the nicotinamide adenine dinucleotide phosphate oxidase-dependent production of reactive oxygen species. Accumulating evidence indicates that Hv1 is expressed in nervous systems, in addition to immune cells and others. Here, we summarize the molecular properties, distribution, and physiological functions of Hv1 in the peripheral and central nervous systems. We describe the recently discovered functions of Hv1 in various neurological diseases, including brain or spinal cord injury, ischemic stroke, demyelinating diseases, and pain. We also summarize the current advances in the discovery and application of Hv1-targeted small molecules in neurological diseases. Finally, we discuss the current limitations of our understanding of Hv1 and suggest future research directions.

Triggering of Major Brain Disorders by Protons and ATP: The Role of ASICs and P2X Receptors / 神经科学通报·英文版

Adenosine triphosphate (ATP) is well-known as a universal source of energy in living cells. Less known is that this molecule has a variety of important signaling functions: it activates a variety of specific metabotropic (P2Y) and ionotropic (P2X) receptors in neuronal and non-neuronal cell membranes. So, a wide variety of signaling functions well fits the ubiquitous presence of ATP in the tissues. Even more ubiquitous are protons. Apart from the unspecific interaction of protons with any protein, many physiological processes are affected by protons acting on specific ionotropic receptors-acid-sensing ion channels (ASICs). Both protons (acidification) and ATP are locally elevated in various pathological states. Using these fundamentally important molecules as agonists, ASICs and P2X receptors signal a variety of major brain pathologies. Here we briefly outline the physiological roles of ASICs and P2X receptors, focusing on the brain pathologies involving these receptors.

Research on Logic Design of Proton Treatment Control System / 中国医疗器械杂志

The proton treatment control system is the supporting software of the proton therapy device, which specifically coordinates and controls the status and work of each subsystem. In this study, the software architecture and hardware implementation of the proton treatment control system was developed and built a foundation for the overall debugging. Using C# programming language and WPF programming techniques, TCP network communication protocol specified by the proton treatment technical document and MVVM pattern in Windows system, the logic design and implementation of each level were studied. Meanwhile, the communication interface between the subsystems under TCP communication protocol was agreed. The logic design and research of the setup field and treatment field were carried out. And the User Interface was designed and developed using the above technology. The program realizes the communication and interaction between the proton treatment control system and each subsystem, so as to control and monitor the whole treatment process. The proton treatment control system provides a software basis for the remote overall debugging and on-line monitor and control of proton treatment device.

Cálculo de potencia de frenado y tiempo de frenado para los protones en los tejidos humanos / Calculation of Stopping Power and Stopping time for Protons in Human Tissues

In this research, the electronic stopping power was calculated using Bethe and Bragg rule equations for the protons in Human tissues (Bone, Muscle (skeletal) and Adipose tissue) all within energy range (0.01-1000) MeV. The equations were programmed using MATLAB 2017, the calculations were compared with the experimental data of the SRIM2013program and PSTAR code, this comparison showed a good agreement with experimental data

Progress in Clinical Research of Amide Proton Transfer Imaging / 中国医疗器械杂志

As a new type of magnetic resonance imaging method, amide proton transfer (APT) imaging can detect the chemical exchange characteristics of free proprotein, peptide amide proton and water proton by water signal changes, reflecting the changes of protein and pH in tissues. In recent years, clinical research on brain tumors, multiple sclerosis, hepatic encephalopathy and cervical cancer have been carried out. It is a radiation-free and non-invasive new magnetic resonance molecular imaging technology. This study briefly reviews the principle of APT technology and its clinical application, and prospects its application prospects in children's abdominal tumors.

Analysis of Key Points of Radiation Sources in Proton and Carbon Ion Radiotherapy Facilities in Shanghai / 中国医疗器械杂志

Compared with conventional high energy X-ray radiotherapy, proton/carbon ion has obvious advantages because of its Bragg peak dose distribution. However, proton heavy ion facility has complex structure, high energy and various radiation types due to various nuclear reaction processes, the radiation protection safety brought by the operation of facilities has gradually attracted attention. Taking the proton/carbon ion radiotherapy facility of Shanghai Proton and Heavy Ion Center as an example, the author mainly analyzed the operation principle of proton/carbon ion treatment facility, the basis of radiation protection, analysis of key radiation source points, etc., so as to provide theoretical support and experience for radiation protection.

Delafloxacin, a New Miracle in Antibiotics Armamentarium for Bacterial Infections

The persistent antibiotics resistant issue has emerged as an influencing factor to deteriorate community health. So, new antibiotics development is urgent for the treatment of bacterial infections. Alternatively, delafloxacin is an eminent new fluoroquinolone, and chemically distinct from older fluoroquinolones. There is lack of proton substituent that indicates the poor acidic property of the drug. It also has a good intracellular penetration capacity that increases the intensity of the bactericidal property in acidic environment. Delafloxacin is a super active drug against the skin and soft tissue infections (SSTIs) and community-acquired respiratory tract infections. Delafloxacin also exhibits better efficacy against pathogens which are resistant to other fluoroquinolones, such as methicillin-resistant Staphylococcus aureus (MRSA). Delafloxacin received approval from the US Food and Drug Administration (FDA) for the treatment of acute bacterial skin and skin structure infections (ABSSI). Phase III clinical trial among patients with community-acquired pneumonia (CAP) is ongoing to evaluate the effectiveness of delafloxacin. From the aforementioned arguments, delafloxacin will be a prominent candidate for the upcoming antibacterial agent. Similarly, delafloxacin can be a crucial drug to fight against ABSSI.

Hemorrhagic Brain Metastasis in Angiosarcoma

Angiosarcomas are rare, but aggressive malignancies. Reports of brain metastasis are uncommon. In this report, we describe the clinical features of a 62 year-old man who presented with hemoptysis and right-sided weakness. Chest computed tomography showed multiple ill-defined part solid nodules in both lungs and brain magnetic resonance imaging showed multiple hemorrhagic bran masses. The patient underwent whole body proton emission tomography to identify biopsy site and showed multiple bone lesions. A right acetabulum biopsy in confirmed the diagnosis of angiosarcoma.

Proton pump inhibitor intake negatively affects the osseointegration of dental implants: a retrospective study

OBJECTIVES: This study sought to investigate the association between the systemic intake of proton pump inhibitors (PPI) and the early failure of dental implants. MATERIALS AND METHODS: A retrospective cohort study involving 1,918 dental implants in 592 patients (69 implants in 24 PPI users and 1,849 implants in 568 nonusers, respectively) was conducted. The effect of PPI intake on the osseointegration of dental implants was evaluated using patient- and implant-level models. RESULTS: Among 24 PPI users, two patients experienced implant failure, one of whom had three and the other of whom had one failed implant, respectively. Thus, the rate of failure for this population was 8.3%. Separately, 11 nonusers each experienced one implant failure, and the failure rate for these patients was 1.9%. Fisher's exact test revealed statistically significant differences between PPI users and nonusers at the implant level (P=0.002) but failed to show any significance at the patient level (P=0.094). The odds of implant failure were 4.60 times greater among PPI users versus nonusers. Dental implants that were placed in patients using PPIs were found to be 4.30 times more likely to fail prior to loading. CONCLUSION: The findings of this study suggest that PPI intake may be associated with an increased risk of early dental implant failure.

Radiation-induced Myositis after Proton Beam Therapy to Huge Hepatocellular Carcinoma

Proton beam therapy (PBT) is one of the advances in radiotherapy techniques, which enables dose escalation with lower probability of radiation-induced liver or gastrointestinal injuries. However, the chest wall proximal to the tumor can be affected by high dose irradiation. Here, we report on a 58-year-old male patient who presented with huge hepatocellular carcinoma, received treatment with transarterial chemoembolization and PBT, and developed severe chest wall pain due to radiation-induced myositis. The patient's symptoms were controlled by oral steroids.

Hepatocellular Carcinoma with Segmental Portal Vein Invasion Exhibiting a Complete Response after Transarterial Radioembolization

The treatment options available for patients with hepatocellular carcinoma (HCC) with portal vein invasion (PVI) include sorafenib, transarterial radioembolization (TARE), radiation therapy (RT), transarterial chemoembolization with RT, and proton beam irradiation. Herein, we present a case of HCC with segmental PVI that was managed via TARE. The patient had a 4 cm HCC that invaded the segment VIII portal vein branch without extrahepatic spread. Liver function was Child-Pugh grade A, and performance status was good. TARE was performed without any adverse events, and a radiological complete response (CR) was achieved. Thereafter, the patient was followed-up every 3–6 months without any further treatment, and the CR was maintained for >3 years. Therefore, TARE may be a useful alternative therapeutic option for patients with HCC exhibiting segmental PVI.

Study of clustered damage in DNA after proton irradiation based on density-based spatial clustering of applications with noise algorithm / 生物医学工程学杂志

The deoxyribonucleic acid (DNA) molecule damage simulations with an atom level geometric model use the traversal algorithm that has the disadvantages of quite time-consuming, slow convergence and high-performance computer requirement. Therefore, this work presents a density-based spatial clustering of applications with noise (DBSCAN) clustering algorithm based on the spatial distributions of energy depositions and hydroxyl radicals (·OH). The algorithm with probability and statistics can quickly get the DNA strand break yields and help to study the variation pattern of the clustered DNA damage. Firstly, we simulated the transportation of protons and secondary particles through the nucleus, as well as the ionization and excitation of water molecules by using Geant4-DNA that is the Monte Carlo simulation toolkit for radiobiology, and got the distributions of energy depositions and hydroxyl radicals. Then we used the damage probability functions to get the spatial distribution dataset of DNA damage points in a simplified geometric model. The DBSCAN clustering algorithm based on damage points density was used to determine the single-strand break (SSB) yield and double-strand break (DSB) yield. Finally, we analyzed the DNA strand break yield variation trend with particle linear energy transfer (LET) and summarized the variation pattern of damage clusters. The simulation results show that the new algorithm has a faster simulation speed than the traversal algorithm and a good precision result. The simulation results have consistency when compared to other experiments and simulations. This work achieves more precise information on clustered DNA damage induced by proton radiation at the molecular level with high speed, so that it provides an essential and powerful research method for the study of radiation biological damage mechanism.

Application Status and Development Trends of Medical Proton and Heavy Ion Accelerators / 中国医疗器械杂志

Cancer therapy with accelerated proton or heavy ion beam is the most advanced radiotherapy technology, which is recognized by the international community at present. It is of great practical significance to study the medical proton and heavy ion accelerators and the radiotherapy technology, in order to promote the development of the advanced medical radiotherapy equipments and improve the quality of life of cancer patients in China. After a brief overview of cancer therapy with proton and heavy ion beam, this paper summarized and analyzed the application status of medical proton accelerators and medical heavy ion accelerators at home and abroad, and finally put forward the future development trends of medical proton and heavy ion accelerators and the radiotherapy technology, it can provide a reference for the progress and development strategies of the advanced radiotherapy equipments in China.

Issues on the Stress Ulcer Prophylaxis Using Proton Pump Inhibitor in Intensive Care Unit / 대한소화기학회지

No abstract available.

Current status of proton therapy techniques for lung cancer

Proton beams have been used for cancer treatment for more than 28 years, and several technological advancements have been made to achieve improved clinical outcomes by delivering more accurate and conformal doses to the target cancer cells while minimizing the dose to normal tissues. The state-of-the-art intensity modulated proton therapy is now prevailing as a major treatment technique in proton facilities worldwide, but still faces many challenges in being applied to the lung. Thus, in this article, the current status of proton therapy technique is reviewed and issues regarding the relevant uncertainty in proton therapy in the lung are summarized.

Feasibility of Spin-Echo Echo-Planar Imaging MR Elastography in Livers of Children and Young Adults

PURPOSE: To assess the feasibility of the use of spin-echo echo-planar imaging (SE-EPI) magnetic resonance elastography (MRE) in livers of children and young adults. MATERIALS AND METHODS: Patients (≤ 20 years old) who underwent 3T SE-EPI MRE were included retrospectively. Subjects were divided into three groups according to the purpose of the liver MRI: suspicion of fatty liver or focal fat deposition in the liver (FAT group), liver fibrosis after receiving a Kasai operation from biliary atresia (BA group), and hepatic iron deposition after receiving chemotherapy or transfusions (IRON group). Technical failure of MRE was defined when a stiffness map showed no pixel value with a confidence index higher than 95%, and the patients were divided as success and failure groups accordingly. Clinical findings including age, gender, weight, height, and body mass index and magnetic resonance imaging results including proton density fat fraction (PDFF), T2*, and MRE values were assessed. Factors affecting failure of MRE were evaluated and the image quality in wave propagation image and stiffness map was evaluated using the appropriate scores. RESULTS: Among total 240 patients (median 15 years, 211 patients in the FAT, 21 patients in the BA, and 8 patients in the IRON groups), technical failure was noted in six patients in the IRON group (6/8 patients, 75%), while there were no failures noted in the FAT and BA groups. These six patients had T2* values ranging from 0.9 to 3.8 ms. The image quality scores were not significantly different between the FAT and BA groups (P > 0.999), while the scores were significantly lower in the IRON group (P < 0.001). CONCLUSION: The 3T SE-EPI MRE in children and young adults had a high technical success rate. The technical failure was occurred in children with decreased T2* value (≤ 3.8 ms) from iron deposition.

Multi-Parametric Quantitative MRI for Measuring Myelin Loss in Hyperglycemia-Induced Hemichorea

Hyperglycemia-induced hemichorea (HGHC) is a rare but characteristic hyperkinetic movement disorder involving limbs on one side of the body. In a 75-year-old woman with a left-sided HGHC, conventional brain MR imaging showed very subtle T1-hyperintensity and unique gadolinium enhancement in the basal ganglia contralateral to movements. Multi-parametric MRI was acquired using pulse sequence with quantification of relaxation times and proton density by multi-echo acquisition. Myelin map was reconstructed based on new tissue classification modeling. In this case report of multi-parametric MRI, quantitative measurement of myelin change related to HGHC in brain structures and its possible explanations are presented. This is the first study to demonstrate myelin loss related to hyperglycemic insult in multi-parametric quantitative MR imaging.

Arterial Spin Labelling Perfusion, Proton MR Spectroscopy and Susceptibility-Weighted MR Findings of Acute Necrotizing Encephalopathy: a Case Report

In this study, we report arterial spin labelling perfusion, proton MR spectroscopy and susceptibility-weighted MR findings of acute necrotizing encephalopathy in a child with rotavirus infection.

IgE-mediated allergy to proton pump inhibitors with both delayed and immediate onset

Proton pump inhibitors (PPIs) are widely used for the treatment of gastrointestinal diseases. Incidence of drug hypersensitivity reactions (DHRs) to PPIs has been rising, presumably because of their increased consumption. Most DHR are IgE-mediated, with half of the reactions being anaphylactic. We describe the case of a Caucasian 50-year-old female patient referred to our allergy department after 2 episodes of anaphylaxis. The allergy work-up distinguished PPI as a cause of delayed onset (14 hours) and immediate onset (45 minutes) IgE-mediated DHR.

Coronal Three-Dimensional Magnetic Resonance Imaging for Improving Diagnostic Accuracy for Posterior Ligamentous Complex Disruption In a Goat Spine Injury Model

OBJECTIVE: The purpose of this study was to investigate whether three-dimensional (3D) magnetic resonance imaging could improve diagnostic accuracy for suspected posterior ligamentous complex (PLC) disruption. MATERIALS AND METHODS: We used 20 freshly harvested goat spine samples with 60 segments and intact surrounding soft tissue. The animals were aged 1–1.5 years and consisted of 8 males and 12 females, which were sexually mature but had not reached adult weights. We created a paraspinal contusion model by percutaneously injecting 10 mL saline into each side of the interspinous ligament (ISL). All segments underwent T2-weighted sagittal and coronal short inversion time inversion recovery (STIR) scans as well as coronal and sagittal 3D proton density-weighted spectrally selective inversion recovery (3D-PDW-SPIR) scans acquired at 1.5T. Following scanning, some ISLs were cut and then the segments were re-scanned using the same magnetic resonance (MR) techniques. Two radiologists independently assessed the MR images, and the reliability of ISL tear interpretation was assessed using the kappa coefficient. The chi-square test was used to compare the diagnostic accuracy of images obtained using the different MR techniques. RESULTS: The interobserver reliability for detecting ISL disruption was high for all imaging techniques (0.776–0.949). The sensitivity, specificity, and diagnostic accuracy of the coronal 3D-PDW-SPIR technique for detecting ISL tears were 100, 96.9, and 97.9%, respectively, which were significantly higher than those of the sagittal STIR (p = 0.000), coronal STIR (p = 0.000), and sagittal 3D-PDW-SPIR (p = 0.001) techniques. CONCLUSION: Compared to other MR methods, coronal 3D-PDW-SPIR provides a more accurate diagnosis of ISL disruption. Adding coronal 3D-PDW-SPIR to a routine MR protocol may help to identify PLC disruptions in cases with nearby contusion.