Gastro-esophageal reflux disease(GERD)is one of the most prevalent chronic diseases.Although proton pump inhibitors(PPIs)represent the mainstay of treatment both for healing erosive esophagitis and for symptom relief,...Gastro-esophageal reflux disease(GERD)is one of the most prevalent chronic diseases.Although proton pump inhibitors(PPIs)represent the mainstay of treatment both for healing erosive esophagitis and for symptom relief,several studies have shown that up to 40%of GERD patients reported either partial or complete lack of response of their symptoms to a standard PPI dose once daily.Several mechanisms have been proposed as involved in PPIs resistance,including ineffective control of gastric acid secretion,esophageal hypersensitivity,ultrastructural and functional changes in the esophageal epithelium.The diagnostic evaluation of a refractory GERD patients should include an accurate clinical evaluation,upper endoscopy,esophageal manometry and ambulatory pH-impedance monitoring,which allows to discriminate non-erosive reflux disease patients from those presenting esophageal hypersensitivity or functional heartburn.Treatment has been primarily based on doubling the PPI dose or switching to another PPI.Patients with proven disease,not responding to PPI twice daily,are eligible for anti-reflux surgery.展开更多
Helicobacter pylori(H.pylori)infection is highly associated with the occurrence of gastrointestinal diseases,including gastric inflammation,peptic ulcer,gastric cancer,and gastric mucosa-associated lymphoid-tissue lym...Helicobacter pylori(H.pylori)infection is highly associated with the occurrence of gastrointestinal diseases,including gastric inflammation,peptic ulcer,gastric cancer,and gastric mucosa-associated lymphoid-tissue lymphoma.Although alternative therapies,including phytomedicines and probiotics,have been used to improve eradication,current treatment still relies on a combination of antimicrobial agents,such as amoxicillin,clarithromycin,metronidazole,and levofloxacin,and antisecretory agents,such as proton pump inhibitors(PPIs).A standard triple therapy consisting of a PPI and two antibiotics(clarithromycin and amoxicillin/metronidazole)is widely used as the first-line regimen for treatment of infection,but the increased resistance of H.pylori to clarithromycin and metronidazole has significantly reduced the eradication rate using this therapy and bismuth-containing therapy or 10-d sequential therapy has therefore been proposed to replace standard triple therapy.Alternatively,levofloxacin-based triple therapy can be used as rescue therapy for H.pylori infection after failure of first-line therapy.The increase in resistance to antibiotics,including levofloxacin,may limit the applicability of such regimens.However,since resistance of H.pylori to amoxicillin is generally low,an optimized high dose dual therapy consisting of a PPI and amoxicillin can be an effective first-line or rescue therapy.In addition,the concomitant use of alternative medicine has the potential to provide additive or synergistic effects against H.pylori infection,though its efficacy needs to be verified in clinical studies.展开更多
The China Spallation Neutron Source （CSNS） is an accelerator-based multidisciplinary user facility to be constructed in Dongguan, Guangdong, China. The CSNS complex consists of an H- linear accelerator, a rapid cycl...The China Spallation Neutron Source （CSNS） is an accelerator-based multidisciplinary user facility to be constructed in Dongguan, Guangdong, China. The CSNS complex consists of an H- linear accelerator, a rapid cycling synchrotron accelerating the beam to 1.6 GeV, a solid-tungsten target station, and instruments for spallation neutron applications. The facility operates at 25 Hz repetition rate with an initial design beam power of 120 kW and is upgradeable to 500 kW. Construction of the CSNS project will lay the foundation of a leading national research center based on advanced proton-accelerator technology, pulsed neutron-scattering technology, and related programs including muon, fast neutron, and proton applications as well as medical therapy and accelerator-driven subcritical reactor （ADS） applications to serve China＇s strategic needs in scientific research and technological innovation for the next 30 plus years.展开更多
In addition to regulating acid secretion, the gastric antral hormone gastrin regulates several important cellular processes in the gastric epithelium including proliferation, apoptosis, migration, invasion, tissue rem...In addition to regulating acid secretion, the gastric antral hormone gastrin regulates several important cellular processes in the gastric epithelium including proliferation, apoptosis, migration, invasion, tissue remodelling and angiogenesis. Elevated serum concentrations of this hormone are caused by many conditions, particularly hypochlorhydria (as a result of autoimmune or Helicobacter pylori (H pylori)-induced chronic atrophic gastritis or acid suppressing drugs) and gastrin producing tumors (gastrinomas). There is now accumulating evidence that altered local and plasma concentrations of gastrin may play a role during the development of various gastric tumors. In the absence of H pylori infection, marked hypergastrinemia frequently results in the development of gastric enterochromaffi n cell-like neuroendocrine tumors and surgery to remove the cause of hypergastrinemia may lead to tumor resolution in this condition. In animal models such as transgenic INS-GAS mice, hypergastrinemia has also been shown to act as a cofactor with Helicobacter infection during gastric adenocarcinoma development. However, it is currently unclear as to what extent gastrin also modulates human gastric adenocarcinoma development. Therapeutic approaches targeting hypergastrinemia,such as immunization with G17DT, have been evaluated for the treatment of gastric adenocarcinoma, with some promising results. Although the mild hypergastrinemia associated with proton pump inhibitor drug use has been shown to cause ECL-cell hyperplasia and to increase H pylori-induced gastric atrophy, there is currently no convincing evidence that this class of agents contributes towards the development of gastric neuroendocrine tumors or gastric adenocarcinomas in human subjects.展开更多
THE incidence of gastroesophageal reflux disease （GERD） is high in Western nations. Its extraesophageal manifestations such as asthma, paroxysmal laryngospasm, and excessive throat phlegm,
The plasma membrane （PM） H^＋-ATPase is an important ion pump in the plant cell membrane. By extruding protons from the cell and generating a membrane potential, this pump energizes the PM, which is a prerequisite f...The plasma membrane （PM） H^＋-ATPase is an important ion pump in the plant cell membrane. By extruding protons from the cell and generating a membrane potential, this pump energizes the PM, which is a prerequisite for growth. Modification of the autoinhibitory terminal domains activates PM H^＋-ATPase activity, and on this basis it has been hypothesized that these regulatory termini are targets for physiological factors that activate or inhibit proton pumping. In this review, we focus on the posttranslational regulation of the PM H＋-ATPase and place regulation of the pump in an evolutionary and physiological context. The emerging picture is that multiple signals regulating plant growth interfere with the posttranslational regulation of the PM H^＋-ATPase.展开更多
AIM： To compare two different daily doses of lansoprazole given for 12 weeks and to assess the role of gastrointestinal （GI） investigations as criteria for selecting patients. METHODS： Out of 45 patients referred ...AIM： To compare two different daily doses of lansoprazole given for 12 weeks and to assess the role of gastrointestinal （GI） investigations as criteria for selecting patients. METHODS： Out of 45 patients referred for unexplained chronic persistent cough, 36 had at least one of the GI investigations （endoscopy, 24-h esophageal pH- metry and a 4-week trial of proton pump inhibitor （PPI） therapy） positive and were randomly assigned to receive either 30 mg lansoprazole o.d. or 30 mg lansoprazole b.i.d, for 12 weeks. Symptoms were evaluated at baseline （visit 1） after the PPI test （visit 2） and after the 12-week lansoprazole treatment period （visit 3）. RESULTS： Thirty-five patients completed the study protocol. Twenty-one patients （60.0%） reported complete relief from their cough with no difference between the two treatment groups （58.8% and 61.1% had no cough in 30 mg lansoprazole and 60 mg lansoprazole groups, respectively）. More than 80% of the patients who had complete relief from their cough at the end of the treatment showed a positive response to the PPI test. CONCLUSION： Twelve weeks of lansoprazole treatment even at a standard daily dose, is effective in patients with chronic persistent cough. A positive response to an initial PPI test seems to be the best criterion for selecting patients who respond to therapy.展开更多
Background Sporadic fundic gland polyps （FGPs） are common gastric polyps.Some studies reported that FGPs dramatically increased due to proton pump inhibitors （PPIs） use and a decreased prevalence of Helicobacter p...Background Sporadic fundic gland polyps （FGPs） are common gastric polyps.Some studies reported that FGPs dramatically increased due to proton pump inhibitors （PPIs） use and a decreased prevalence of Helicobacter pylori （H.pylon） infection in Western countries.However,data are still controversial.This study aimed to identify the relationships between these two factors and FGPs in China.Methods Consecutive patients with FGPs detected were retrospectively analyzed.Data including patients＇ age,sex,symptoms,H.pylori infection,history of PPIs use,and the polyps were documented.Each patient was compared with two randomly selected age-and sex-matched controls with similar symptoms in the same period.Results During the period from March 2011 to March 2012,a total of 328 patients were diagnosed as FGPs in 23 047 patients who underwent routine esophagogastroduodenoscopy and 656 patients without FGPs as controls.The mean age was （55.12±12.61） years,and 75.91％ were women.The prevalence of H.pylori in patients with FGPs was significantly lower than in those without FGPs （22.30％ （64/287） vs.42.26％ （224/530）,P ＜0.001,OR 0.392,95％ Cl 0.283-0.544）.Overall,a total of 54 patients with FGPs （54/328,16.46％） and 136 patients without FGPs （136/656,20.73％） received PPIs therapy （P=0.110）.According to the different duration of PPIs use,no significant differences of PPIs use were found between the cases and controls among all subgroups.Moreover,the PPIs use was also similar,regardless of age,sex,H.pylori infection,and the number of polyps.Conclusion Sporadic FGPs may not be induced by PPIs therapy but negatively correlate with H.pylori infection in China,which is not the same with the data in Western countries.展开更多
The cure rates of Helicobacter pylori (H. pylori) eradication therapy using a proton pump inhibitor (PPI) and antimicrobial agents such as amoxicillin, clarithromycin, and metronidazole are mainly influenced by bacter...The cure rates of Helicobacter pylori (H. pylori) eradication therapy using a proton pump inhibitor (PPI) and antimicrobial agents such as amoxicillin, clarithromycin, and metronidazole are mainly influenced by bacterial susceptibility to antimicrobial agents and the magnitude of the inhibition of acid secretion. Annual cure rates have gradually decreased because of the increased prevalence of H. pylori strains resistant to antimicrobial agents, especially to clarithromycin. Alternative regimens have therefore been developed incorporating different antimicrobial agents. Further, standard PPI therapy (twice-daily dosing) often fails to induce a long-term increase in intragastric pH > 4.0. Increasing the eradication rate requires more frequent and higher doses of PPIs. Therapeutic efficacy related to acid secretion is influenced by genetic factors such as variants of the genes encoding drug-metabolizing enzymes (e.g., cytochrome P450 2C19, CYP2C19), drug transporters (e.g., multidrug resistance protein-1; ABCB1), and inflammatory cytokines (e.g., interleukin-1β). For example, quadruple daily administration of PPI therapy potently inhibits acid secretion within 24 h, irrespective of CYP2C19 genotype. Therefore, tailored H. pylori eradication regimens that address acid secretion and employ optimal antimicrobial agents based on results of antimicrobial agent-susceptibility testing may prove effective in attaining higher eradication rates.展开更多
Background：Amide proton transfer （APT） imaging has recently emerged as an important contrast mechanism for magnetic resonance imaging （MRI） in the field of molecular and cellular imaging.The aim of this study was...Background：Amide proton transfer （APT） imaging has recently emerged as an important contrast mechanism for magnetic resonance imaging （MRI） in the field of molecular and cellular imaging.The aim of this study was to evaluate the feasibility of APT imaging to detect cerebral abnormality in patients with Alzheimer＆#39;s disease （AD） at 3.0 Tesla.Methods：Twenty AD patients （9 men and 11 women; age range,67-83 years） and 20 age-matched normal controls （11 men and 9 women; age range,63-82 years） underwent APT and traditional MRI examination on a 3.0 Tesla MRI system.The magnetic resonance ratio asymmetry （MTRasym） values at 3.5 ppm of bilateral hippocampi （Hc）,temporal white matter regions,occipital white matter regions,and cerebral peduncles were measured on oblique axial APT images.MTRasym （3.5 ppm） values of the cerebral structures between AD patients and control subjects were compared with independent samples t-test.Controlling for age,partial correlation analysis was used to investigate the associations between mini-mental state examination （MMSE） and the various MRI measures among AD patients.Results：Compared with normal controls,MTRasym （3.5 ppm） values of bilateral Hc were significantly increased in AD patients （right 1.24% ± 0.21% vs.0.83% ± 0.19%,left 1.18% ± 0.18% vs.0.80%± 0.17%,t =3.039,3.328,P =0.004,0.002,respectively）.MTRasym （3.5 ppm） values of bilateral Hc were significantly negatively correlated with MMSE （right r =-0.559,P =0.013; left r=-0.461,P =0.047）.Conclusions：Increased MTRasym （3.5 ppm） values of bilateral Hc in AD patients and its strong correlations with MMSE suggest that APT imaging could potentially provide imaging biomarkers for the noninvasive molecular diagnosis of AD.展开更多
Stress-related mucosal disease is a typical complication of critically ill patients in the intensive care unit(ICU). It poses a risk of clinically relevant upper gastrointestinal(GI) bleeding. Therefore, stress ulcer ...Stress-related mucosal disease is a typical complication of critically ill patients in the intensive care unit(ICU). It poses a risk of clinically relevant upper gastrointestinal(GI) bleeding. Therefore, stress ulcer prophylaxis(SUP)is recommended in high-risk patients, especially those mechanically ventilated > 48 h and those with a manifest coagulopathy. Proton pump inhibitors(PPI) and, less effectively, histamine 2 receptor antagonists(H2RA) prevent GI bleeding in critically ill patients in the ICU. However, the routine use of pharmacological SUP does not reduce overall mortality in ICU patients. Moreover, recent studies revealed that SUP in the ICU might be associated with potential harm such as an increased risk of infectious complications, especially nosocomial pneumonia and Clostridium difficile-associated diarrhea. Additionally, special populations such as patients with liver cirrhosis may even have an increased mortality rate if treated with PPI. Likewise, PPI can be toxic for both the liver and the bone marrow, and some PPI show clinically relevant interactions with important other drugs like clopidogrel. Therefore, the agent of choice, the specific balance of risks and benefits for individual patients as well as the possible dose of PPI has to be chosen carefully. Alternatives to PPI prophylaxis include H2 RA and/or sucralfate. Instead of routine SUP, further trials should investigate risk-adjusted algorithms, balancing benefits and threats of SUP medication in the ICU.展开更多
AIM:To evaluate the effect of efflux pump inhibitors (EPIs) on multidrug resistance of Helicobacter pylori (H. pylori).METHODS: H. pylori strains were isolated and cultured on Brucella agar plates with 10% sheep's...AIM:To evaluate the effect of efflux pump inhibitors (EPIs) on multidrug resistance of Helicobacter pylori (H. pylori).METHODS: H. pylori strains were isolated and cultured on Brucella agar plates with 10% sheep's blood. The multidrug resistant (MDR) H. pylori were obtained with the inducer chloramphenicol by repeated doubling of the concentration until no colony was seen, then the susceptibilities of the MDR strains and their parents to 9 antibiotics were assessed with agar dilution tests. The present study included periods before and after the advent of the EPIs, carbonyl cyanide m-chlorophenyl hydrazone (CCCP), reserpine and pantoprazole), and the minimum inhibitory concentrations (MICs) were determined accordingly. In the same way, the effects of 5 proton pump inhibitors (PPIs), used in treatment of H. pylori infection, on MICs of antibiotics were evaluated.RESULTS: Four strains of MDR H. pylori were induced successfully, and the antibiotic susceptibilities of MDR strains were partly restored by CCCP and pantoprazole, but there was little effect of reserpine. Rabeprazole was the most effective of the 5 PPIs which could decrease the MICs of antibiotics for MDR H. pylori significantly.CONCLUSION: In vitro, some EPIs can strengthen the activities of different antibiotics which are the putative substrates of the efflux pump system in H. pylori.展开更多
Objective To investigate the value of in vivo proton magnetic resonance spectroscopy （MRS） in the assessment of hepatocelhilar carcinoma （HCC） and monitor its metabolic change shortly after transcatheter arterial ...Objective To investigate the value of in vivo proton magnetic resonance spectroscopy （MRS） in the assessment of hepatocelhilar carcinoma （HCC） and monitor its metabolic change shortly after transcatheter arterial chemoembolization （TACE）. Mothoda In this prospective study, 28 consecutive patients with large HCC （ ≥3 cm in diameter） confirmed by fine needle aspiration biopsy were recruited. The ^1H MRS of all hepatic lesions and some uninvolved liver parenchyma were performed with 1.5T whole body MR scanner. Among them, 15 cases were evaluated again about one week after TACE. The main metabolites such as choline and lipid before and after interventional therapy were measured to assess the early response of the tumor. The technical success rate of IH MRS in liver was high （33/41, 80% ）, closely related to breath motion, location of lesion, and size of voxeL In spectra, the choline compound peak of HCC elevated compared with uninvolved liver parenchyma. After TACE, both the amplitude and the area of choline resonance peak significantly descended （ choline-to-lipid ratios from 0.352±0. 080 to 0. 167±0. 030, P = 0. 026; from 0. 205±0. 060 to 0. 070±0. 020, P = 0. 042, respectively ） ; yet lipid resonance peak ascended. Conclusions In vivo tH MRS is technically feasible for the evaluation of large focal hepatic lesions, however, the reproducibility and stability are not as good as routine MR scan. IH MRS can monitor the early stage metabolic changes of HCC after TACE but limitation like quantification still exists.展开更多
Today,Pt/C catalysts are widely used in proton exchange membrane fuel cells(PEMFCs).The practical applications of PEMFCs still face many limitations in the preparation of advanced Pt‐based catalysts,including high co...Today,Pt/C catalysts are widely used in proton exchange membrane fuel cells(PEMFCs).The practical applications of PEMFCs still face many limitations in the preparation of advanced Pt‐based catalysts,including high cost,limited life‐time,and insufficient power density.A kinetically sluggish oxygen reduction reaction(ORR)is primarily responsible for these issues.The development of advanced Pt‐based catalysts is crucial for solving these pro-blems when the large‐scale application of PEMFCs is to be realized.Herein,we demonstrate the design principle of advanced Pt‐based catalysts with an emphasis on theoretical understandings to practical applications.Generally,three main strategies(including strain effect,electronic effect,and ensemble effect)that governing the initial activity of Pt‐based electrocatalysts are ela-borated in detail in this review.Recent advanced Pt‐based ORR catalysts are summarized and we present representative achievements to further reveal the relationship of excellent ORR performance based on theoretical mechanisms.Then we focus on the preparation standards of membrane electrode assembles and testing protocols in practice.Finally,we predict the remaining challenges and present our perspectives with regards to design strategies for improving ORR performance of Pt‐based catalysts in the future.展开更多
Various Ionic and molecular activities in the extraceUular environment are vital to plant cell physiological processes. A noninvasive microsensing system （NMS） based on either the scanning ion-selective electrode te...Various Ionic and molecular activities in the extraceUular environment are vital to plant cell physiological processes. A noninvasive microsensing system （NMS） based on either the scanning ion-selective electrode technique （SIET） or the scanning polarographlc electrode technique （SPET） is able to obtain information regarding the transportation of various Ions/molecules in Intact samples under normal physiological conditions. The two-probe simultaneous test system （2STS） Is an Integrated system composed of SIET, SPET, and a Xu-Kunkel sampling protocol. In the present study, 2STS was able to simultaneously measure fluxes of H^＋ and O2 of the Uly （Lillum Iongiflorum Thunb. cv. Ace） pollen tube while avoiding interference between the two probes. The results Indicate that the proton fluxes were effluxes, whereas the oxygen fluxes were Influxes, and they were closely correlated to each other surrounding the constitutive alkaline band region. Specifically, when the proton effluxes increased, the oxygen Influxes also increased. Therefore, the hypothesis of condensed active mitochondria existing in the alkalized area of the pollen tube proposed by Hepler＇s group is supported.展开更多
Due to the restrictions of liver transplantation,complication-guided pharmacological therapy has become the mainstay of long-term management of cirrhosis.This article aims to provide a complete overview of pharmacothe...Due to the restrictions of liver transplantation,complication-guided pharmacological therapy has become the mainstay of long-term management of cirrhosis.This article aims to provide a complete overview of pharmacotherapy options that may be commenced in the outpatient setting which are available for managing cirrhosis and its complications,together with discussion of current controversies and potential future directions.PubMed/Medline/Cochrane Library were electronically searched up to December 2018 to identify studies evaluating safety,efficacy and therapeutic mechanisms of pharmacological agents in cirrhotic adults and animal models of cirrhosis.Non-selective betablockers effectively reduce variceal re-bleeding risk in cirrhotic patients with moderate/large varices,but appear ineffective for primary prevention of variceal development and may compromise renal function and haemodynamic stability in advanced decompensation.Recent observational studies suggest protective,haemodynamically-independent effects of beta-blockers relating to reduced bacterial translocation.The gut-selective antibiotic rifaximin is effective for secondary prophylaxis of hepatic encephalopathy;recent small trials also indicate its potential superiority to norfloxacin for secondary prevention of spontaneous bacterial peritonitis.Diuretics remain the mainstay of uncomplicated ascites treatment,and early trials suggest alpha-adrenergic receptor agonists may improve diuretic response in refractory ascites.Vaptans have not demonstrated clinical effectiveness in treating refractory ascites and may cause detrimental complications.Despite initial hepatotoxicity concerns,safety of statin administration has been demonstrated in compensated cirrhosis.Furthermore,statins are suggested to have protective effects upon fibrosis progression,decompensation and mortality.Evidence as to whether proton pump inhibitors cause gut-liver-brain axis dysfunction is conflicting.Emerging evidence indicates that anticoagulation therapy reduces incidence and increases展开更多
AIM To perform a systematic review and meta-analysis on proton pump inhibitors(PPIs) therapy and the risk of Clostridium difficile infection(CDI). METHODS We conducted a systematic search of MEDLINE/Pub Med and seven ...AIM To perform a systematic review and meta-analysis on proton pump inhibitors(PPIs) therapy and the risk of Clostridium difficile infection(CDI). METHODS We conducted a systematic search of MEDLINE/Pub Med and seven other databases through January 1990 to March 2017 for published studies that evaluated the association between PPIs and CDI. Adult case-control and cohort studies providing information on the association between PPI therapy and the development of CDI were included. Pooled odds ratios(ORs) estimates with 95% confidence intervals(CIs) were calculated using the random effect. Heterogeneity was assessed by I^2 test and Cochran's Q statistic.Potential publication bias was evaluated via funnel plot, and quality of studies by the Newcastle-Otawa Quality Assessment Scale(NOS). RESULTS Fifty-six studies(40 case-control and 16 cohort) involving 356683 patients met the inclusion criteria and were analyzed. Both the overall pooled estimates and subgroup analyses showed increased risk for CDI despite substantial statistical heterogeneity among studies. Meta-analysis of all studies combined showed a significant association between PPI users and the risk of CDI(pooled OR = 1.99, CI: 1.73-2.30, P < 0.001) as compared with non-users. The association remained significant in subgroup analyses: by design-case-control(OR = 2.00, CI: 1.68-2.38, P < 0.0001), and cohort(OR = 1.98, CI: 1.51-2.59, P < 0.0001); adjusted(OR = 1.95, CI: 1.67-2.27, P < 0.0001) and unadjusted(OR = 2.02, CI: 1.41-2.91, P < 0.0001); unicenter(OR = 2.18, CI: 1.72-2.75, P < 0.0001) and multicenter(OR = 1.82, CI: 1.51-2.19, P < 0.0001); age ≥ 65 years(OR = 1.93, CI: 1.40-2.68, P < 0.0001) and < 65 years(OR = 2.06, CI: 1.11-3.81, P < 0.01). No significant differences were found in subgroup analyses(test for heterogeneity): P = 0.93 for case-control vs cohort, P = 0.85 for adjusted vs unadjusted, P = 0.24 for unicenter vs multicenter, P = 0.86 for age ≥ 65 years and < 65 years. There was significant heterogeneity across studies(I^2 = 85.4%, P < 0.00展开更多
文摘Gastro-esophageal reflux disease(GERD)is one of the most prevalent chronic diseases.Although proton pump inhibitors(PPIs)represent the mainstay of treatment both for healing erosive esophagitis and for symptom relief,several studies have shown that up to 40%of GERD patients reported either partial or complete lack of response of their symptoms to a standard PPI dose once daily.Several mechanisms have been proposed as involved in PPIs resistance,including ineffective control of gastric acid secretion,esophageal hypersensitivity,ultrastructural and functional changes in the esophageal epithelium.The diagnostic evaluation of a refractory GERD patients should include an accurate clinical evaluation,upper endoscopy,esophageal manometry and ambulatory pH-impedance monitoring,which allows to discriminate non-erosive reflux disease patients from those presenting esophageal hypersensitivity or functional heartburn.Treatment has been primarily based on doubling the PPI dose or switching to another PPI.Patients with proven disease,not responding to PPI twice daily,are eligible for anti-reflux surgery.
文摘Helicobacter pylori(H.pylori)infection is highly associated with the occurrence of gastrointestinal diseases,including gastric inflammation,peptic ulcer,gastric cancer,and gastric mucosa-associated lymphoid-tissue lymphoma.Although alternative therapies,including phytomedicines and probiotics,have been used to improve eradication,current treatment still relies on a combination of antimicrobial agents,such as amoxicillin,clarithromycin,metronidazole,and levofloxacin,and antisecretory agents,such as proton pump inhibitors(PPIs).A standard triple therapy consisting of a PPI and two antibiotics(clarithromycin and amoxicillin/metronidazole)is widely used as the first-line regimen for treatment of infection,but the increased resistance of H.pylori to clarithromycin and metronidazole has significantly reduced the eradication rate using this therapy and bismuth-containing therapy or 10-d sequential therapy has therefore been proposed to replace standard triple therapy.Alternatively,levofloxacin-based triple therapy can be used as rescue therapy for H.pylori infection after failure of first-line therapy.The increase in resistance to antibiotics,including levofloxacin,may limit the applicability of such regimens.However,since resistance of H.pylori to amoxicillin is generally low,an optimized high dose dual therapy consisting of a PPI and amoxicillin can be an effective first-line or rescue therapy.In addition,the concomitant use of alternative medicine has the potential to provide additive or synergistic effects against H.pylori infection,though its efficacy needs to be verified in clinical studies.
基金Supported by Chinese Academy of Sciences, Guangdong Provincial Government, Dongguan Municipal Government, CAS Hundred People Initiative (KJCX2-YW-N22)Overseas Outstanding Youth Program of National Natural Science Foundation of China (10628510)
文摘The China Spallation Neutron Source （CSNS） is an accelerator-based multidisciplinary user facility to be constructed in Dongguan, Guangdong, China. The CSNS complex consists of an H- linear accelerator, a rapid cycling synchrotron accelerating the beam to 1.6 GeV, a solid-tungsten target station, and instruments for spallation neutron applications. The facility operates at 25 Hz repetition rate with an initial design beam power of 120 kW and is upgradeable to 500 kW. Construction of the CSNS project will lay the foundation of a leading national research center based on advanced proton-accelerator technology, pulsed neutron-scattering technology, and related programs including muon, fast neutron, and proton applications as well as medical therapy and accelerator-driven subcritical reactor （ADS） applications to serve China＇s strategic needs in scientific research and technological innovation for the next 30 plus years.
基金Supported by Wellcome Trust Clinical Research Training Fellowship to MDB
文摘In addition to regulating acid secretion, the gastric antral hormone gastrin regulates several important cellular processes in the gastric epithelium including proliferation, apoptosis, migration, invasion, tissue remodelling and angiogenesis. Elevated serum concentrations of this hormone are caused by many conditions, particularly hypochlorhydria (as a result of autoimmune or Helicobacter pylori (H pylori)-induced chronic atrophic gastritis or acid suppressing drugs) and gastrin producing tumors (gastrinomas). There is now accumulating evidence that altered local and plasma concentrations of gastrin may play a role during the development of various gastric tumors. In the absence of H pylori infection, marked hypergastrinemia frequently results in the development of gastric enterochromaffi n cell-like neuroendocrine tumors and surgery to remove the cause of hypergastrinemia may lead to tumor resolution in this condition. In animal models such as transgenic INS-GAS mice, hypergastrinemia has also been shown to act as a cofactor with Helicobacter infection during gastric adenocarcinoma development. However, it is currently unclear as to what extent gastrin also modulates human gastric adenocarcinoma development. Therapeutic approaches targeting hypergastrinemia,such as immunization with G17DT, have been evaluated for the treatment of gastric adenocarcinoma, with some promising results. Although the mild hypergastrinemia associated with proton pump inhibitor drug use has been shown to cause ECL-cell hyperplasia and to increase H pylori-induced gastric atrophy, there is currently no convincing evidence that this class of agents contributes towards the development of gastric neuroendocrine tumors or gastric adenocarcinomas in human subjects.
文摘THE incidence of gastroesophageal reflux disease （GERD） is high in Western nations. Its extraesophageal manifestations such as asthma, paroxysmal laryngospasm, and excessive throat phlegm,
文摘The plasma membrane （PM） H^＋-ATPase is an important ion pump in the plant cell membrane. By extruding protons from the cell and generating a membrane potential, this pump energizes the PM, which is a prerequisite for growth. Modification of the autoinhibitory terminal domains activates PM H^＋-ATPase activity, and on this basis it has been hypothesized that these regulatory termini are targets for physiological factors that activate or inhibit proton pumping. In this review, we focus on the posttranslational regulation of the PM H＋-ATPase and place regulation of the pump in an evolutionary and physiological context. The emerging picture is that multiple signals regulating plant growth interfere with the posttranslational regulation of the PM H^＋-ATPase.
文摘AIM： To compare two different daily doses of lansoprazole given for 12 weeks and to assess the role of gastrointestinal （GI） investigations as criteria for selecting patients. METHODS： Out of 45 patients referred for unexplained chronic persistent cough, 36 had at least one of the GI investigations （endoscopy, 24-h esophageal pH- metry and a 4-week trial of proton pump inhibitor （PPI） therapy） positive and were randomly assigned to receive either 30 mg lansoprazole o.d. or 30 mg lansoprazole b.i.d, for 12 weeks. Symptoms were evaluated at baseline （visit 1） after the PPI test （visit 2） and after the 12-week lansoprazole treatment period （visit 3）. RESULTS： Thirty-five patients completed the study protocol. Twenty-one patients （60.0%） reported complete relief from their cough with no difference between the two treatment groups （58.8% and 61.1% had no cough in 30 mg lansoprazole and 60 mg lansoprazole groups, respectively）. More than 80% of the patients who had complete relief from their cough at the end of the treatment showed a positive response to the PPI test. CONCLUSION： Twelve weeks of lansoprazole treatment even at a standard daily dose, is effective in patients with chronic persistent cough. A positive response to an initial PPI test seems to be the best criterion for selecting patients who respond to therapy.
基金This study was supported by grants from the National Natural Science Foundation of China （No.81300272 and No.81070283）,Research Fund for the Doctoral Program of Higher Education of China （No.20121202110018）,and Tianjin Research Program of Application Foundation and Advanced Technology of China （No.13JCQNJC10600）.
文摘Background Sporadic fundic gland polyps （FGPs） are common gastric polyps.Some studies reported that FGPs dramatically increased due to proton pump inhibitors （PPIs） use and a decreased prevalence of Helicobacter pylori （H.pylon） infection in Western countries.However,data are still controversial.This study aimed to identify the relationships between these two factors and FGPs in China.Methods Consecutive patients with FGPs detected were retrospectively analyzed.Data including patients＇ age,sex,symptoms,H.pylori infection,history of PPIs use,and the polyps were documented.Each patient was compared with two randomly selected age-and sex-matched controls with similar symptoms in the same period.Results During the period from March 2011 to March 2012,a total of 328 patients were diagnosed as FGPs in 23 047 patients who underwent routine esophagogastroduodenoscopy and 656 patients without FGPs as controls.The mean age was （55.12±12.61） years,and 75.91％ were women.The prevalence of H.pylori in patients with FGPs was significantly lower than in those without FGPs （22.30％ （64/287） vs.42.26％ （224/530）,P ＜0.001,OR 0.392,95％ Cl 0.283-0.544）.Overall,a total of 54 patients with FGPs （54/328,16.46％） and 136 patients without FGPs （136/656,20.73％） received PPIs therapy （P=0.110）.According to the different duration of PPIs use,no significant differences of PPIs use were found between the cases and controls among all subgroups.Moreover,the PPIs use was also similar,regardless of age,sex,H.pylori infection,and the number of polyps.Conclusion Sporadic FGPs may not be induced by PPIs therapy but negatively correlate with H.pylori infection in China,which is not the same with the data in Western countries.
基金Supported by Grant-in-aid from the Ministry of Education,Culture,Sports,Science and Technology of Japan,No.22790640 and No.24590912
文摘The cure rates of Helicobacter pylori (H. pylori) eradication therapy using a proton pump inhibitor (PPI) and antimicrobial agents such as amoxicillin, clarithromycin, and metronidazole are mainly influenced by bacterial susceptibility to antimicrobial agents and the magnitude of the inhibition of acid secretion. Annual cure rates have gradually decreased because of the increased prevalence of H. pylori strains resistant to antimicrobial agents, especially to clarithromycin. Alternative regimens have therefore been developed incorporating different antimicrobial agents. Further, standard PPI therapy (twice-daily dosing) often fails to induce a long-term increase in intragastric pH > 4.0. Increasing the eradication rate requires more frequent and higher doses of PPIs. Therapeutic efficacy related to acid secretion is influenced by genetic factors such as variants of the genes encoding drug-metabolizing enzymes (e.g., cytochrome P450 2C19, CYP2C19), drug transporters (e.g., multidrug resistance protein-1; ABCB1), and inflammatory cytokines (e.g., interleukin-1β). For example, quadruple daily administration of PPI therapy potently inhibits acid secretion within 24 h, irrespective of CYP2C19 genotype. Therefore, tailored H. pylori eradication regimens that address acid secretion and employ optimal antimicrobial agents based on results of antimicrobial agent-susceptibility testing may prove effective in attaining higher eradication rates.
文摘Background：Amide proton transfer （APT） imaging has recently emerged as an important contrast mechanism for magnetic resonance imaging （MRI） in the field of molecular and cellular imaging.The aim of this study was to evaluate the feasibility of APT imaging to detect cerebral abnormality in patients with Alzheimer＆#39;s disease （AD） at 3.0 Tesla.Methods：Twenty AD patients （9 men and 11 women; age range,67-83 years） and 20 age-matched normal controls （11 men and 9 women; age range,63-82 years） underwent APT and traditional MRI examination on a 3.0 Tesla MRI system.The magnetic resonance ratio asymmetry （MTRasym） values at 3.5 ppm of bilateral hippocampi （Hc）,temporal white matter regions,occipital white matter regions,and cerebral peduncles were measured on oblique axial APT images.MTRasym （3.5 ppm） values of the cerebral structures between AD patients and control subjects were compared with independent samples t-test.Controlling for age,partial correlation analysis was used to investigate the associations between mini-mental state examination （MMSE） and the various MRI measures among AD patients.Results：Compared with normal controls,MTRasym （3.5 ppm） values of bilateral Hc were significantly increased in AD patients （right 1.24% ± 0.21% vs.0.83% ± 0.19%,left 1.18% ± 0.18% vs.0.80%± 0.17%,t =3.039,3.328,P =0.004,0.002,respectively）.MTRasym （3.5 ppm） values of bilateral Hc were significantly negatively correlated with MMSE （right r =-0.559,P =0.013; left r=-0.461,P =0.047）.Conclusions：Increased MTRasym （3.5 ppm） values of bilateral Hc in AD patients and its strong correlations with MMSE suggest that APT imaging could potentially provide imaging biomarkers for the noninvasive molecular diagnosis of AD.
基金The German Research Foundation,No.DFG Ta434/5-1the Interdisciplinary Center for Clinical Research(IZKF)Aachen
文摘Stress-related mucosal disease is a typical complication of critically ill patients in the intensive care unit(ICU). It poses a risk of clinically relevant upper gastrointestinal(GI) bleeding. Therefore, stress ulcer prophylaxis(SUP)is recommended in high-risk patients, especially those mechanically ventilated > 48 h and those with a manifest coagulopathy. Proton pump inhibitors(PPI) and, less effectively, histamine 2 receptor antagonists(H2RA) prevent GI bleeding in critically ill patients in the ICU. However, the routine use of pharmacological SUP does not reduce overall mortality in ICU patients. Moreover, recent studies revealed that SUP in the ICU might be associated with potential harm such as an increased risk of infectious complications, especially nosocomial pneumonia and Clostridium difficile-associated diarrhea. Additionally, special populations such as patients with liver cirrhosis may even have an increased mortality rate if treated with PPI. Likewise, PPI can be toxic for both the liver and the bone marrow, and some PPI show clinically relevant interactions with important other drugs like clopidogrel. Therefore, the agent of choice, the specific balance of risks and benefits for individual patients as well as the possible dose of PPI has to be chosen carefully. Alternatives to PPI prophylaxis include H2 RA and/or sucralfate. Instead of routine SUP, further trials should investigate risk-adjusted algorithms, balancing benefits and threats of SUP medication in the ICU.
基金Supported by Henan Distinguished Junior Scholar Grant,No.074100510017
文摘AIM:To evaluate the effect of efflux pump inhibitors (EPIs) on multidrug resistance of Helicobacter pylori (H. pylori).METHODS: H. pylori strains were isolated and cultured on Brucella agar plates with 10% sheep's blood. The multidrug resistant (MDR) H. pylori were obtained with the inducer chloramphenicol by repeated doubling of the concentration until no colony was seen, then the susceptibilities of the MDR strains and their parents to 9 antibiotics were assessed with agar dilution tests. The present study included periods before and after the advent of the EPIs, carbonyl cyanide m-chlorophenyl hydrazone (CCCP), reserpine and pantoprazole), and the minimum inhibitory concentrations (MICs) were determined accordingly. In the same way, the effects of 5 proton pump inhibitors (PPIs), used in treatment of H. pylori infection, on MICs of antibiotics were evaluated.RESULTS: Four strains of MDR H. pylori were induced successfully, and the antibiotic susceptibilities of MDR strains were partly restored by CCCP and pantoprazole, but there was little effect of reserpine. Rabeprazole was the most effective of the 5 PPIs which could decrease the MICs of antibiotics for MDR H. pylori significantly.CONCLUSION: In vitro, some EPIs can strengthen the activities of different antibiotics which are the putative substrates of the efflux pump system in H. pylori.
基金Supported by National Natural Sciences Foundation of China(30470503)
文摘Objective To investigate the value of in vivo proton magnetic resonance spectroscopy （MRS） in the assessment of hepatocelhilar carcinoma （HCC） and monitor its metabolic change shortly after transcatheter arterial chemoembolization （TACE）. Mothoda In this prospective study, 28 consecutive patients with large HCC （ ≥3 cm in diameter） confirmed by fine needle aspiration biopsy were recruited. The ^1H MRS of all hepatic lesions and some uninvolved liver parenchyma were performed with 1.5T whole body MR scanner. Among them, 15 cases were evaluated again about one week after TACE. The main metabolites such as choline and lipid before and after interventional therapy were measured to assess the early response of the tumor. The technical success rate of IH MRS in liver was high （33/41, 80% ）, closely related to breath motion, location of lesion, and size of voxeL In spectra, the choline compound peak of HCC elevated compared with uninvolved liver parenchyma. After TACE, both the amplitude and the area of choline resonance peak significantly descended （ choline-to-lipid ratios from 0.352±0. 080 to 0. 167±0. 030, P = 0. 026; from 0. 205±0. 060 to 0. 070±0. 020, P = 0. 042, respectively ） ; yet lipid resonance peak ascended. Conclusions In vivo tH MRS is technically feasible for the evaluation of large focal hepatic lesions, however, the reproducibility and stability are not as good as routine MR scan. IH MRS can monitor the early stage metabolic changes of HCC after TACE but limitation like quantification still exists.
基金NSFC,Grant/Award Numbers:21871159,21890383National Key R&D Program of China,Grant/Award Numbers:2018YFA0702003,2016YFA0202801+2 种基金National Natural Science Foundation of China,Grant/Award Numbers:21890383,21671117,21871159Science and Technology Key Project of Guangdong Province of China,Grant/Award Number:2020B010188002Beijing Municipal Science&Technology Commission,Grant/Award Number:Z191100007219003。
文摘Today,Pt/C catalysts are widely used in proton exchange membrane fuel cells(PEMFCs).The practical applications of PEMFCs still face many limitations in the preparation of advanced Pt‐based catalysts,including high cost,limited life‐time,and insufficient power density.A kinetically sluggish oxygen reduction reaction(ORR)is primarily responsible for these issues.The development of advanced Pt‐based catalysts is crucial for solving these pro-blems when the large‐scale application of PEMFCs is to be realized.Herein,we demonstrate the design principle of advanced Pt‐based catalysts with an emphasis on theoretical understandings to practical applications.Generally,three main strategies(including strain effect,electronic effect,and ensemble effect)that governing the initial activity of Pt‐based electrocatalysts are ela-borated in detail in this review.Recent advanced Pt‐based ORR catalysts are summarized and we present representative achievements to further reveal the relationship of excellent ORR performance based on theoretical mechanisms.Then we focus on the preparation standards of membrane electrode assembles and testing protocols in practice.Finally,we predict the remaining challenges and present our perspectives with regards to design strategies for improving ORR performance of Pt‐based catalysts in the future.
基金Supported by the National Natural Science Foundation of China （30170552）, Beijing Natural Science Foundation （5042004）, Beijing Education Committee Science and Technology Development Project （KM200410028015） and Applicable Electronics Inc. （Forestdale, MA, USA）.
文摘Various Ionic and molecular activities in the extraceUular environment are vital to plant cell physiological processes. A noninvasive microsensing system （NMS） based on either the scanning ion-selective electrode technique （SIET） or the scanning polarographlc electrode technique （SPET） is able to obtain information regarding the transportation of various Ions/molecules in Intact samples under normal physiological conditions. The two-probe simultaneous test system （2STS） Is an Integrated system composed of SIET, SPET, and a Xu-Kunkel sampling protocol. In the present study, 2STS was able to simultaneously measure fluxes of H^＋ and O2 of the Uly （Lillum Iongiflorum Thunb. cv. Ace） pollen tube while avoiding interference between the two probes. The results Indicate that the proton fluxes were effluxes, whereas the oxygen fluxes were Influxes, and they were closely correlated to each other surrounding the constitutive alkaline band region. Specifically, when the proton effluxes increased, the oxygen Influxes also increased. Therefore, the hypothesis of condensed active mitochondria existing in the alkalized area of the pollen tube proposed by Hepler＇s group is supported.
基金Supported by The Division of Integrative Systems Medicine and Digestive Disease at Imperial College London receives financial support from the National Institute for Health Research(NIHR)Imperial Biomedical Research Centre(BRC)based at Imperial College Healthcare NHS Trust and Imperial College Londonfunded by the NIHR BRC
文摘Due to the restrictions of liver transplantation,complication-guided pharmacological therapy has become the mainstay of long-term management of cirrhosis.This article aims to provide a complete overview of pharmacotherapy options that may be commenced in the outpatient setting which are available for managing cirrhosis and its complications,together with discussion of current controversies and potential future directions.PubMed/Medline/Cochrane Library were electronically searched up to December 2018 to identify studies evaluating safety,efficacy and therapeutic mechanisms of pharmacological agents in cirrhotic adults and animal models of cirrhosis.Non-selective betablockers effectively reduce variceal re-bleeding risk in cirrhotic patients with moderate/large varices,but appear ineffective for primary prevention of variceal development and may compromise renal function and haemodynamic stability in advanced decompensation.Recent observational studies suggest protective,haemodynamically-independent effects of beta-blockers relating to reduced bacterial translocation.The gut-selective antibiotic rifaximin is effective for secondary prophylaxis of hepatic encephalopathy;recent small trials also indicate its potential superiority to norfloxacin for secondary prevention of spontaneous bacterial peritonitis.Diuretics remain the mainstay of uncomplicated ascites treatment,and early trials suggest alpha-adrenergic receptor agonists may improve diuretic response in refractory ascites.Vaptans have not demonstrated clinical effectiveness in treating refractory ascites and may cause detrimental complications.Despite initial hepatotoxicity concerns,safety of statin administration has been demonstrated in compensated cirrhosis.Furthermore,statins are suggested to have protective effects upon fibrosis progression,decompensation and mortality.Evidence as to whether proton pump inhibitors cause gut-liver-brain axis dysfunction is conflicting.Emerging evidence indicates that anticoagulation therapy reduces incidence and increases
文摘AIM To perform a systematic review and meta-analysis on proton pump inhibitors(PPIs) therapy and the risk of Clostridium difficile infection(CDI). METHODS We conducted a systematic search of MEDLINE/Pub Med and seven other databases through January 1990 to March 2017 for published studies that evaluated the association between PPIs and CDI. Adult case-control and cohort studies providing information on the association between PPI therapy and the development of CDI were included. Pooled odds ratios(ORs) estimates with 95% confidence intervals(CIs) were calculated using the random effect. Heterogeneity was assessed by I^2 test and Cochran's Q statistic.Potential publication bias was evaluated via funnel plot, and quality of studies by the Newcastle-Otawa Quality Assessment Scale(NOS). RESULTS Fifty-six studies(40 case-control and 16 cohort) involving 356683 patients met the inclusion criteria and were analyzed. Both the overall pooled estimates and subgroup analyses showed increased risk for CDI despite substantial statistical heterogeneity among studies. Meta-analysis of all studies combined showed a significant association between PPI users and the risk of CDI(pooled OR = 1.99, CI: 1.73-2.30, P < 0.001) as compared with non-users. The association remained significant in subgroup analyses: by design-case-control(OR = 2.00, CI: 1.68-2.38, P < 0.0001), and cohort(OR = 1.98, CI: 1.51-2.59, P < 0.0001); adjusted(OR = 1.95, CI: 1.67-2.27, P < 0.0001) and unadjusted(OR = 2.02, CI: 1.41-2.91, P < 0.0001); unicenter(OR = 2.18, CI: 1.72-2.75, P < 0.0001) and multicenter(OR = 1.82, CI: 1.51-2.19, P < 0.0001); age ≥ 65 years(OR = 1.93, CI: 1.40-2.68, P < 0.0001) and < 65 years(OR = 2.06, CI: 1.11-3.81, P < 0.01). No significant differences were found in subgroup analyses(test for heterogeneity): P = 0.93 for case-control vs cohort, P = 0.85 for adjusted vs unadjusted, P = 0.24 for unicenter vs multicenter, P = 0.86 for age ≥ 65 years and < 65 years. There was significant heterogeneity across studies(I^2 = 85.4%, P < 0.00
