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

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.

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.

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.

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.

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.

New Perspectives in Pediatric Nonalcoholic Fatty Liver Disease: Epidemiology, Genetics, Diagnosis, and Natural History / 대한소아소화기영양학회지

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children. The global prevalence of pediatric NAFLD from general populations is 7.6%. In obese children, the prevalence is higher in Asia. NAFLD has a strong heritable component based on ethnic difference in the prevalence and clustering within families. Genetic polymorphisms of patatin-like phospholipase domain–containing protein 3 (PNPLA3), transmembrane 6 superfamily member 2, and glucokinase regulatory protein (GCKR) are associated with the risk of NAFLD in children. Variants of PNPLA3 and GCKR are more common in Asians. Alterations of the gut microbiome might contribute to the pathogenesis of NAFLD. High fructose intake increases the risk of NAFLD. Liver fibrosis is a poor prognostic factor for disease progression to cirrhosis. Magnetic resonance spectroscopy and magnetic resonance proton density fat fraction are more accurate for steatosis quantification than ultrasound. Noninvasive imaging methods to assess liver fibrosis, such as transient elastography, shear-wave elastography, and magnetic resonance elastography are useful in predicting advanced fibrosis, but they need further validation. Longitudinal follow-up studies into adulthood are needed to better understand the natural history of pediatric NAFLD.

Is the Diagnostic Trial with Proton Pump Inhibitors Reasonable for School Age Children with Gastroesophageal Reflux Symptoms? / 대한소아소화기영양학회지

PURPOSE: On the basis of evidence, we aimed to reevaluate the necessity of the empirical proton pump inhibitor (PPI) trial for children with suspected gastroesophageal reflux disease (GERD). METHODS: We analyzed the frequency of GERD in 85 school-age children with gastroesophageal reflux (GER) symptoms, who received 24-hour esophageal pH monitoring and/or upper endoscopy. According to the reflux index (RI), the children were classified into normal (RI <5%), intermediate (5%≤ RI <10%), or abnormal (RI ≥10%) groups. RESULTS: Fifty six were female and 29 were male. Their mean age was 12.6±0.5 (±standard deviation) years (range: 6.8–18.6). The RI analysis showed that the normal group included 76 patients (89.4%), the intermediate group included 6 patients (7.1%), and the abnormal group included 3 patients (3.5%). The DeMeester score was 5.93±4.65, 14.68±7.86 and 40.37±12.96 for the normal, intermediate and abnormal group, respectively (p=0.001). The longest reflux time was 5.56±6.00 minutes, 9.53±7.84 minutes, and 19.46±8.35 minutes in the normal, intermediate, and abnormal group, respectively (p=0.031). Endoscopic findings showed reflux esophagitis in 7 patients. On the basis of the Los Angeles Classification of Esophagitis, 5 of these patients were included in group A, 1 patient, in group B and 1 patient, in group C. CONCLUSION: The incidence of GERD was very low in school-age children with GER symptoms. Therefore, injudicious diagnostic PPI trials would be postponed until the actual prevalence of GERD is verified in future prospective studies.

Can proton pump inhibitors cause intestinal inflammation in children? / 소아과

No abstract available.

Influence of proton pump inhibitor therapy on intestinal inflammation assessed by fecal calprotectin in pediatric patients / 소아과

BACKGROUND: An increase in the numbers of patients with gastrointestinal symptoms has recently been observed. PURPOSE: To investigate the effects of proton pump inhibitor (PPI) therapy on intestinal inflammation in children and adolescents as confirmed by clinical manifestations and objectively assessed by fecal calprotectin (FC) level measurement. METHODS: Consecutive children (aged 3–18 years) who presented with gastrointestinal symptoms and were treated with or without PPI for at least 1 month were enrolled. Patients were divided into PPI and non-PPI groups. The PPI group was further subdivided by treatment duration and type of PPI used. Stool samples were collected for FC evaluation at baseline and after treatment and clinical data and FC levels were compared between the groups. RESULTS: Fifty-one patients (15 boys, 36 girls) were enrolled in the study. The PPI group included 37 patients, while the non-PPI group included 14 patients. Clinical symptoms were not significantly different. FC levels and laboratory results, including C-reactive protein levels, white blood cell count, and absolute neutrophil count, were not statistically different before versus after PPI treatment. After treatment, FC levels decreased to 8.1 mg/kg (-575.4 to 340.3 mg/kg) in the PPI group and increased to 5.6 mg/kg (-460.0 to 186.9 mg/kg) in the non-PPI group compared to those before treatment (P=0.841). The number of patients with increased FC levels was not significantly different between the 2 groups (48.6% vs. 64.3%, P=0.363), similar to that observed in patients with an FC level > 50 mg/kg (24.3% and 7.1%, P=0.250). PPI therapy type and duration did not affect the FC levels (P=0.811 and P=0.502, respectively). CONCLUSION: Although we aimed to confirm the evidence of intestinal inflammation due to PPI use in children and adolescents through clinical symptoms and FC measurement, no significant changes were observed.

Effects of Proton Pump Inhibitor for Laryngopharyngeal Reflux and Comorbid Chronic Rhinosinusitis / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Laryngopharyngeal reflux (LPR) is a prevalent condition with an increasing incidence, and several recent studies have reported the association of LPR with chronic rhinosinusitis (CRS). In this study, we studied the effect of proton-pump inhibitors (PPIs) on symptom improvement for LPR and comorbid CRS. SUBJECTS AND METHOD: Enrolled in the study from January 2017 to December 2017 were 164 patients (54 male, 110 female, mean age 48.8 years) who were diagnosed as LPR by reflux symptom index (RSI) or reflux finding scores (RFS) and comorbid CRS. Sino-Nasal Outcome Test (SNOT)-20 and Lund-Kennedy endoscopic scores were evaluated for CRS severity. The study group was divided into PPI treatment group (Ilaprazole 20 mg, once a day for 8 weeks) and non-treatment group. The RSI, RFS, SNOT-20, and Lund-Kennedy endoscopic scores were repeated at the end of treatment. RESULTS: Ninety-two patients were prescribed PPI and 72 patients were not. Initial RSI, RFS, SNOT-20, and Lund-Kennedy score did not differ between the two groups. RSI and RFS decreased significantly after eight weeks of PPI medication (p=0.002 and p<0.001, respectively). In the non-treatment group, only RFS showed statistically significant decrease. SNOT-20 and Lund-Kennedy endoscopic scores decreased significantly in the treatment group (p=0.005 and p<0.001, respectively) compared to the non-treatment group. CONCLUSION: The results of our study suggest that PPI treatment for 8 weeks was effective in reducing signs and symptoms of both LPR and CRS.

Onion peel extract and its constituent, quercetin inhibits human Slo3 in a pH and calcium dependent manner

Sperm function and male fertility are closely related to pH dependent K⁺ current (KSper) in human sperm, which is most likely composed of Slo3 and its auxiliary subunit leucine-rich repeat-containing protein 52 (LRRC52). Onion peel extract (OPE) and its major active ingredient quercetin are widely used as fertility enhancers; however, the effect of OPE and quercetin on Slo3 has not been elucidated. The purpose of this study is to investigate the effect of quercetin on human Slo3 channels. Human Slo3 and LRRC52 were co-transfected into HEK293 cells and pharmacological properties were studied with the whole cell patch clamp technique. We successfully expressed and measured pH sensitive and calcium insensitive Slo3 currents in HEK293 cells. We found that OPE and its key ingredient quercetin inhibit Slo3 currents. Inhibition by quercetin is dose dependent and this degree of inhibition decreases with elevating internal alkalization and internal free calcium concentrations. Functional moieties in the quercetin polyphenolic ring govern the degree of inhibition of Slo3 by quercetin, and the composition of such functional moieties are sensitive to the pH of the medium. These results suggest that quercetin inhibits Slo3 in a pH and calcium dependent manner. Therefore, we surmise that quercetin induced depolarization in spermatozoa may enhance the voltage gated proton channel (Hv1), and activate non-selective cation channels of sperm (CatSper) dependent calcium influx to trigger sperm capacitation and acrosome reaction.

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.