proton

摘要： The plant vacuole plays a fundamental role in cell homeostasis.The successful application of patch-clamp technique on isolated vacuoles allows the determination of the functional characteristics of tonoplast ion channels and transporters.The parallel use of a sensor-based fluorescence approach capable of detecting changes in calcium and proton concentrations opens up new possibilities for investigation.In excised patch,the presence of fura-2 in the vacuolar solution reveals the direct permeation of calcium in plant TPC channels.In whole-vacuole,the activity of non-electrogenic NHX potassium proton antiporters can be measured by using the proton sensitive dye BCECF loaded in the vacuolar lumen by the patch pipette.Both vacuolar NHXs and CLCa(chloride/nitrate antiporter)are inhibited by the phosphoinositide PI(3,5)P2,suggesting a coordinated role of these proteins in salt accumulation.Increased knowledge in the molecular mechanisms of vacuolar ion channels and transporters has the potential to improve our understanding on how plants cope with a rapidly changing environment.

摘要： BACKGROUND The exact mechanism of proton pump inhibitors(PPIs)-induced hypomagnesemia(PPIH) is largely unknown. Previous studies proposed that PPIH is a consequence of intestinal Mg2+ malabsorption. However, the mechanism of PPIs-suppressed intestinal Mg2+ absorption is under debate.AIM To investigate the effect of 12-wk and 24-wk omeprazole injection on the total,transcellular, and paracellular Mg2+ absorption in the duodenum, jejunum, ileum,and colon of male Sprague-Dawley rats.METHODS The rats received 20 mg/kg·d subcutaneous omeprazole injection for 12 or 24 wk.Plasma and urinary Mg2+, Ca2+, and PO43-levels were measured. The plasma concentrations of 1α,25-dihydroxyvitamin D3(1α,25(OH)2D3), parathyroid hormone(PTH), fibroblast growth factor 23(FGF-23), epidermal growth factor(EGF), and insulin were also observed. The duodenum, jejunum, ileum, and colon of each rat were mounted onto individual modified Using chamber setups to study the rates of total, transcellular, and paracellular Mg2+ absorption simultaneously. The expression of transient receptor potential melastatin 6(TRPM6) and cyclin M4(CNNM4) in the entire intestinal tract was also measured.RESULTS Single-dose omeprazole injection significantly increased the intraluminal p H of the stomach, duodenum, and jejunum. Omeprazole injection for 12 and 24 wk induced hypomagnesemia with reduced urinary Mg2+ excretion. The plasma Ca2+ was normal but the urinary Ca2+ excretion was reduced in rats with PPIH. The plasma and urinary PO43-levels increased in PPIH rats. The levels of1α,25(OH)2D3 and FGF-23 increased, whereas that of plasma EGF decreased in the omeprazole-treated rats. The rates of the total, transcellular, and paracellular Mg2+ absorption was significantly lower in the duodenum, jejunum, ileum, and colon of the rats with PPIH than in those of the control rats. The percent suppression of Mg2+ absorption in the duodenum, jejunum, ileum, and colon of the rats with PPIH compared with the control rats was 81.86%, 70.59%, 69.45%,and 39.25%, respectively. Compared with the control rats, the rats with PPIH had significantly higher TRPM6 and CNNM4 expression levels throughout the intestinal tract.CONCLUSION Intestinal Mg2+ malabsorption was observed throughout the intestinal tract of rats with PPIH. PPIs mainly suppressed small intestinal Mg2+ absorption. Omeprazole exerted no effect on the intraluminal acidic pH in the colon. Thus, the lowest percent suppression of total Mg2+ absorption was found in the colon. The expression levels of TRPM6 and CNNM4 increased, indicating the presence of a compensatory response to Mg2+ malabsorption in rats with PPIH. Therefore, the small intestine is an appropriate segment that should be modulated to counteract PPIH.

摘要： Hepatocellular carcinoma(HCC)is the fifth most common malignancy and the second leading cause of cancer mortality worldwide.The cornerstone to improving the prognosis of HCC patients has been the control of loco-regional disease progression and the lesser toxicities of local treatment.Although radiotherapy has not been considered a preferred treatment modality for HCC,charged particle therapy(CPT),including proton beam therapy(PBT)and carbon ion radiotherapy(CIRT),possesses advantages(for example,it allows ablative radiation doses to be applied to tumors but simultaneously spares the normal liver parenchyma from radiation)and has emerged as an alternative treatment option for HCC.With the technological advancements in CPT,various radiation dosages of CPT have been used for HCC treatment via CPT.However,the efficacy and safety of the evolving dosages remain uncertain.To assess the association between locoregional control of HCC and the dose and regimen of CPT,we provide a brief overview of selected literature on dose regimens from conventional to hypofractionated short-course CPT in the treatment of HCC and the subsequent determinants of clinical outcomes.Overall,CPT provides a better local control rate compared with photon beam therapy,ranging from 80%to 96%,and a 3-year overall survival ranging from 50%to 75%,and it results in rare grade 3 toxicities of the late gastrointestinal tract(including radiation-induced liver disease).Regarding CPT for the treatment of locoregional HCC,conventional CPT is preferred to treat central tumors of HCC to avoid late toxicities of the biliary tract.In contrast,the hypo-fractionation regimen of CPT is suggested for treatment of larger-sized tumors of HCC to overcome potential radio-resistance.

摘要： BACKGROUND Liver cirrhosis is the late stage of hepatic fibrosis and is characterized by portal hypertension that can clinically lead to decompensation in the form of ascites,esophageal/gastric varices or encephalopathy.The most common sequelae associated with liver cirrhosis are neurologic and neuropsychiatric impairments labeled as hepatic encephalopathy(HE).Well established triggers for HE include infection,gastrointestinal bleeding,constipation,and medications.Alterations to the gut microbiome is one of the leading ammonia producers in the body,and therefore may make patients more susceptible to HE.AIM To investigate the relationship between the use of proton pump inhibitors(PPIs)and HE in patients with cirrhosis.METHODS This is a single center,retrospective analysis.Patients were included in the study with an admitting diagnosis of HE.The degree of HE was determined from subjective and objective portions of hospital admission notes using the West Haven Criteria.The primary outcome of the study was to evaluate the grade of HE in PPI users versus non-users at admission to the hospital and throughout their hospital course.Secondary outcomes included rate of infection,gastrointestinal bleeding within the last 12 mo,mean ammonia level,and model for end-stage liver disease scores at admission.RESULTS The HE grade at admission using the West Haven Criteria was 2.3 in the PPI group compared to 1.7 in the PPI nonuser group(P=0.001).The average length of hospital stay in PPI group was 8.3 d compared to 6.5 d in PPI nonusers(P=0.046).Twenty-seven(31.8%)patients in the PPI user group required an Intensive Care Unit admission during their hospital course compared to 6 in the PPI nonuser group(16.7%)(P=0.138).Finally,10(11.8%)patients in the PPI group expired during their hospital stay compared to 1 in the PPI nonuser group(2.8%)(P=0.220).CONCLUSION Chronic PPI use in cirrhotic patients is associated with significantly higher average West Haven Criteria for HE compared to patients that do not use PPIs.

摘要： BACKGROUND Locoregional recurrence of breast cancer is challenging for clinicians,due to the various former treatments patients have undergone.However,treatment of the recurrence with systemic therapy and subsequent reirradiation of chest wall is accompanied by increased toxicities,particularly radiation-induced cardiovascular disease.Reirradiation by proton beam therapy(PBT)enables superior preservation of adjacent organs at risk as well as concurrent dose escalation for delivery to the gross tumor.This technology is expected to improve the overall outcome of recurrent breast cancer.CASE SUMMARY A 47-year-old female presented with an extensive locoregional recurrence at 10 yr after primary treatment of a luminal A breast cancer.Because of tumor progression despite having undergone bilateral ovarectomy and systemic therapy,the patient was treated with PBT BE total dose of 64.40 Gy to each gross tumor and 56.00 Gy to the upper mediastinal and retrosternal lymphatics including the entire sternum in 28 fractions.Follow-up computed tomography showed a partial remission,without evidence of newly emerging metastasis.At 19 mo after the PBT,the patient developed a radiation-induced pericardial disease and pleural effusions with clinical burden of dyspnea,which were successfully treated by drainage and corticosteroid.Cytological analysis of the puncture fluid showed no malignancy,and the subsequent computed tomography scan indicated stable disease as well as significantly decreased pericardial and pleural effusions.The patient remains free of progression to date.CONCLUSION PBT was a safe and effective method of reirradiation for locoregionally recurrent breast cancer in our patient.

摘要： BACKGROUND Proton pump inhibitors(PPIs)are widely prescribed,often without clear indications.There are conflicting data on its association with mortality risk and hepatic decompensation in cirrhotic patients.Furthermore,PPI users and PPI exposure in some studies have been poorly defined with many confounding factors.AIM To examine if PPI use increases mortality and hepatic decompensation and the impact of cumulative PPI dose exposure.METHODS Data from patients with decompensated liver cirrhosis were extracted from a hospital database between 2013 to 2017.PPI users were defined as cumulative defined daily dose(cDDD)≥28 within a landmark period,after hospitalisation for hepatic decompensation.Cox regression analysis for comparison was done after propensity score adjustment.Further risk of hepatic decompensation was analysed by Poisson regression.RESULTS Among 295 decompensated cirrhosis patients,238 were PPI users and 57 were non-users.PPI users had higher mortality compared to non-users[adjusted HR=2.10,(1.20-3.67);P=0.009].Longer PPI use with cDDD>90 was associated with higher mortality,compared to non-users[aHR=2.27,(1.10-5.14);P=0.038].PPI users had a higher incidence of hospitalization for hepatic decompensation[aRR=1.61,(1.30-2.11);P90 increases the risk of mortality.

摘要： Many upper gastrointestinal(GI) endoscopies worldwide are performed for inappropriate indications. This overuse of healthcare negatively affects healthcare quality and puts pressure on endoscopy services. Dyspepsia is one of the most common inappropriate indications for upper GI endoscopy as diagnostic yield is low. Reasons for untimely referral are: unfamiliarity with dyspepsia guidelines,uncertainty about etiology of symptoms, and therapy failure. Unfiltered openaccess referrals feed upper GI endoscopy overuse. This review highlights strategies applied to diminish use of upper GI endoscopies for dyspepsia. First,we describe the impact of active guideline implementation. We found improved guideline adherence, but resistance was encountered in the process. Secondly, we show several forms of clinical assessment. While algorithm use reduced upper GI endoscopy volume, effects of referral assessment of individual patients were minor. A third strategy proposed Helicobacter pylori test and treat for all dyspeptic patients. Many upper GI endoscopies can be avoided using this strategy, but outcomes may be prevalence dependent. Lastly, empirical treatment with Proton pump inhibitors achieved symptom relief for dyspepsia and avoided upper GI endoscopies in about two thirds of patients. Changing referral behavior is complex as contributing factors are manifold. A collaboration of multiple strategies is most likely to succeed.

摘要： The main purpose of this article is to demonstrate that electromagnetic and gravitational phenomenology are two different expressions of the same interaction that we can call “universal interaction”. In order to reach the aim, it is therefore necessary to imagine the matter in a slightly different way, as well as equivalent, to what has been done until today by the literature everywhere accepted. Even if differently imagined, this proposed structure of matter cannot and must not escape from reflecting the measurements and phenomenologies widely experimented in laboratories all over the world. In the proposed model the proton radius;the electron mass;the Avogadro constant;the existence and the mass of neutron and the existence of neutrino are theoretically derived. The main consequence is therefore a more general rewriting of Newton’s law of universal gravitation. A definitive value for the universal gravitational constant is proposed.

摘要： Background and Aim: Irradiation methods such as double scattering method and spot scanning method have been used in proton beam treatment devices. In the scattering method, a ridge filter or a range modulation wheel is used to create a spread-out Bragg peak, but the distribution at the patient position may change due to positional deviation of the incident beam. Therefore, assessment of the incident position of the beam is very important even in the scattering method. To investigate the width and distribution of the proton beam before entering the RMW, a radiochromic film was installed at the outlet of the transport pipe and the entrance of the profile-monitoring detector. Methods: In this study, the distributions of the beam at the exit of the transport pipe and the entrance of the monitor detector were measured using films. The beam width was measured from the full width at half maximum of the profile obtained from the distribution. Measurements were conducted every month for 10 months. Results: Beams of widths ranging from 1.82 to 2.30 mm in the horizontal direction and 4.25 to 5.33 mm in the vertical direction were outputted from the exit of the transport pipe. Beams of widths ranging from 2.16 to 2.67 mm in the horizontal direction and 4.06 to 5.31 mm in the vertical direction were outputted from the entrance of the monitor detector. The maximum width fluctuation for 10 months was 0.55 mm in the horizontal direction and 1.26 mm in the vertical direction at the entrance of the monitor detector. Conclusions: The distribution was obtained before the proton beam was scattered by the scatterer, and then we propose a method to periodically measure and monitor the changes in the beam distributions every month.

摘要： 本发明公开了一种用于Ion Proton测序平台的TN5建库的引物组、试剂盒和建库方法。其中，引物组包括用于接头包埋的SEQ ID NO：1‑3所示的序列，以及用于PCR扩增的SEQ ID NO：4‑5所示的序列。本发明提供的引物组使得TN5转座酶能够高效、快速、微量的构建适于Ion Proton的文库，构建的文库可以直接上机测序。不仅摒弃了原始的复杂文库构建程序，而且操作简单，测序结果稳定。

摘要： 本发明属于基因测序领域，公开了一种基于Ion？ProtonTM测序平台的小片段DNA文库的构建方法以及相关的试剂组合溶液。本发明的构建方法包括样品DNA提取、末端修复、片段筛选、接头连接、PCR扩增、文库检测和高通量测序等步骤。在末端修复、接头连接和PCR扩增步骤中分别采用试剂I、试剂II和试剂III。本发明的构建方法步骤精简、操作简单、试剂种类少、成本低、降低了文库的损失和浪费、提高了劳动效率。此外，本发明的构建方法可用于基于Ion？ProtonTM测序平台的孕妇外周血胎儿染色体非整倍体的无创产前诊断，诊断结果准确率高且安全经济，能够帮助有效控制染色体非整倍体胎儿的出生率。

摘要： 本发明公开了一种用于Ion？Proton测序平台的TN5建库的引物组、试剂盒和建库方法。其中，引物组包括用于接头包埋的SEQ？ID？NO：1-3所示的序列，以及用于PCR扩增的SEQ？ID？NO：4-5所示的序列。本发明提供的引物组使得TN5转座酶能够高效、快速、微量的构建适于Ion？Proton的文库，构建的文库可以直接上机测序。不仅摒弃了原始的复杂文库构建程序，而且操作简单，测序结果稳定。

摘要： 本发明公开了一种基于Ion ProtonTM测序平台的血液游离DNA的文库构建方法、试剂及其应用，构建过程包括血液游离DNA提取、末端修复、片段选择、接头连接、磁珠纯化、文库扩增、文库检测、高通量测序等步骤。本发明还提供一种用于构建基于Ion ProtonTM测序平台的血液游离DNA文库的血液游离DNA提取试剂、末端修复试剂、接头连接反应试剂、扩增试剂。本发明明显提高了孕妇血浆胎儿游离DNA的提取浓度，且步骤简单，成本低，提高了建库的成功率；优化后的文库构建体系更利于操作，节省成本，且更换磁珠后，纯化回收效率更高；文库扩增也不需凑够样本量和二次检测，操作更加简单。本发明方法更适用于胎儿染色体非整倍体无创产前诊断。

摘要： 本发明提供了一种基于Proton的转录组测序数据的比较分析方法和系统。其中，该方法包括通过Proton测序平台获取某一物种至少两个转录组的原始测序数据；过滤掉不合格数据，获得clean reads；然后进行第一步分析和第二步分析，其中，所述第一步分析包括：将clean reads分别比对到所述物种的参考基因组；进行转录本定量分析；筛选出显著差异表达的基因；进行显著差异表达基因功能分析；所述第二步分析包括：将clean reads分别比对到所述物种的参考基因组；进行可变剪接分析；进行基因结构优化分析；进行新转录本预测；进行SNP分析；进行基因融合检测。本发明的方法和系统可以提高转录组测序数据比较分析的准确度和可靠性。

摘要： 本发明属于基因测序领域，公开了一种基于Ion ProtonTM测序平台的小片段DNA文库的构建方法以及相关的试剂组合溶液。本发明的构建方法包括样品DNA提取、末端修复、片段筛选、接头连接、PCR扩增、文库检测和高通量测序等步骤。在末端修复、接头连接和PCR扩增步骤中分别采用试剂I、试剂II和试剂III。本发明的构建方法步骤精简、操作简单、试剂种类少、成本低、降低了文库的损失和浪费、提高了劳动效率。此外，本发明的构建方法可用于基于Ion ProtonTM测序平台的孕妇外周血胎儿染色体非整倍体的无创产前诊断，诊断结果准确率高且安全经济，能够帮助有效控制染色体非整倍体胎儿的出生率。