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Background Currently, the data on the relationship between obesity and gastroesophageal reflux disease (GERD) in Asian populations are scarce. Methods The aim of this study is to investigate the prevalence of reflux esophagitis (RE) among obese Japanese patients in each body mass index (BMI) range group. In addition, we aim to investigate the risk factors for RE in obese Japanese patients. The present retrospective cohort study included 674 obese Japanese patients who underwent bariatric surgery between January 2003 and April 2016. The patients were stratified into five groups based on BMI range. Results The mean BMI was 42.7 ± 9.24 kg/m2. The prevalence of RE among each of the groups was as follows: Group 1 (BMI 30–34.9) = 20.7%; Group 2 (BMI 35–39.9) = 24.0%; Group 3 (BMI 40–44.9) = 25.2%; Group 4 (BMI 45–49.9) = 26.7%; and Group 5 (BMI ≥50) = 24.8%. Overall, the prevalence of RE was 24.2% in our study. Furthermore, no significant difference in BMI was noted between the RE and non‐RE groups (43.4 ± 9.3 kg/m2 and 42.5 ± 10.2 kg/m2, respectively; p = 0.24). According to the multivariate logistic regression model, gender, Helicobacter pylori infection status, GERD‐related symptoms, and hiatal hernia were significantly correlated with RE. Conclusion Our study shows that the prevalence of RE in severely obese Japanese patients was significantly higher than the average prevalence of RE in Japan. However, the prevalence of RE did not increase with BMI in our cohort., Our study is the first to report the prevalence of RE in severely obese Japanese patients. Although it has certain limitations, it can still provide valuable reference data in epidemiology.

Autoimmune gastritis (AIG) is a chronic inflammatory condition in gastric mucosa and is associated with increased cancer risk, though not as high as that by Helicobacter pylori (H. pylori)-associated gastritis (HPG). Although aberrant DNA methylation is induced by HPG and the level correlates with the risk of gastric cancer, DNA methylation induction by AIG is unknown.Gastric mucosa samples from the corpus were collected from 12 people with AIG without H. pylori infection, 10 people with HPG, and eight healthy volunteers. Genome-wide DNA methylation analysis was conducted using Infinium Methylation EPIC array. Gene expression was analyzed by quantitative RT-PCR.The AIG samples had extensive aberrant DNA methylation but presented unique methylation profiles against the HPG samples after correction of leucocyte fractions. Comparison between the AIG and HPG samples showed that AIG induced methylation, but less than HPG, in overall CpG sites and also in promoter CpG islands. Promoter CpG islands of tumor-suppressor genes in the pathway of cell cycle, cell adhesion, p53, and WNT were highly methylated in the AIG samples, but more so in the HPG samples. The expression levels of IL1B and IL8, secreted by macrophage, were significantly lower in the AIG samples than in the HPG samples, suggesting that a difference in inflammatory response affected the degree and patterns of aberrant DNA methylation.AIG induced aberrant DNA methylation in gastric mucosa. However, the degree of DNA methylation was less than that by HPG, which reflected carcinogenic risk.

Aggressive social interactions are used to compete for limited resources and are regulated by complex sensory cues and the organism’s internal state. While both sexes exhibit aggression, its neuronal underpinnings are understudied in females. Here, we identify a population of sexually dimorphic aIPg neurons in the adultDrosophila melanogastercentral brain whose optogenetic activation increased, and genetic inactivation reduced, female aggression. Analysis of GAL4 lines identified in an unbiased screen for increased female chasing behavior revealed the involvement of another sexually dimorphic neuron, pC1d, and implicated aIPg and pC1d neurons as core nodes regulating female aggression. Connectomic analysis demonstrated that aIPg neurons and pC1d are interconnected and suggest that aIPg neurons may exert part of their effect by gating the flow of visual information to descending neurons. Our work reveals important regulatory components of the neuronal circuitry that underlies female aggressive social interactions and provides tools for their manipulation.

The neural circuits responsible for animal behavior remain largely unknown. We summarize new methods and present the circuitry of a large fraction of the brain of the fruit fly Drosophila melanogaster. Improved methods include new procedures to prepare, image, align, segment, find synapses in, and proofread such large data sets. We define cell types, refine computational compartments, and provide an exhaustive atlas of cell examples and types, many of them novel. We provide detailed circuits consisting of neurons and their chemical synapses for most of the central brain. We make the data public and simplify access, reducing the effort needed to answer circuit questions, and provide procedures linking the neurons defined by our analysis with genetic reagents. Biologically, we examine distributions of connection strengths, neural motifs on different scales, electrical consequences of compartmentalization, and evidence that maximizing packing density is an important criterion in the evolution of the fly’s brain., eLife digest Animal brains of all sizes, from the smallest to the largest, work in broadly similar ways. Studying the brain of any one animal in depth can thus reveal the general principles behind the workings of all brains. The fruit fly Drosophila is a popular choice for such research. With about 100,000 neurons – compared to some 86 billion in humans – the fly brain is small enough to study at the level of individual cells. But it nevertheless supports a range of complex behaviors, including navigation, courtship and learning. Thanks to decades of research, scientists now have a good understanding of which parts of the fruit fly brain support particular behaviors. But exactly how they do this is often unclear. This is because previous studies showing the connections between cells only covered small areas of the brain. This is like trying to understand a novel when all you can see is a few isolated paragraphs. To solve this problem, Scheffer, Xu, Januszewski, Lu, Takemura, Hayworth, Huang, Shinomiya et al. prepared the first complete map of the entire central region of the fruit fly brain. The central brain consists of approximately 25,000 neurons and around 20 million connections. To prepare the map – or connectome – the brain was cut into very thin 8nm slices and photographed with an electron microscope. A three-dimensional map of the neurons and connections in the brain was then reconstructed from these images using machine learning algorithms. Finally, Scheffer et al. used the new connectome to obtain further insights into the circuits that support specific fruit fly behaviors. The central brain connectome is freely available online for anyone to access. When used in combination with existing methods, the map will make it easier to understand how the fly brain works, and how and why it can fail to work correctly. Many of these findings will likely apply to larger brains, including our own. In the long run, studying the fly connectome may therefore lead to a better understanding of the human brain and its disorders. Performing a similar analysis on the brain of a small mammal, by scaling up the methods here, will be a likely next step along this path.

Precise, repeatable genetic access to specific neurons via the GAL4/UAS system and related methods is a key advantage of Drosophila neuroscience. Neuronal targeting is typically documented using light microscopy of full GAL4 expression patterns, which mostly lack the single-cell resolution required for reliable cell type identification. Here we use stochastic GAL4 labeling with the MultiColor FlpOut approach to generate cellular resolution confocal images at large scale. We are releasing aligned images of 27,000 such adult central nervous systems. An anticipated use of this resource is to bridge the gap between electron microscopy-identified neurons and light microscopy-based intersectional genetic approaches such as the split-GAL4 system. Identifying the individual neurons that make up each GAL4 expression pattern improves the prediction of which GAL4 enhancer fragments best combine via split-GAL4 to target neurons of interest. To this end we have developed the NeuronBridge search tool, which matches these light microscope neuronal images to neurons in the recently published FlyEM hemibrain. This work thus provides a resource and search tool that will significantly enhance both the efficiency and efficacy of split-GAL4 targeting of EM-identified neurons and further advance Drosophila neuroscience.

Aggressive social interactions are used to compete for limited resources and are regulated by complex sensory cues and the organism’s internal state. While both sexes exhibit aggression, its neuronal underpinnings are understudied in females. Here, we describe a set of connected neurons in the adultDrosophila melanogastercentral brain that drive female aggression. We identified a population of sexually dimorphic aIPg neurons whose optogenetic activation increased, and genetic inactivation reduced, female aggression. Analysis of GAL4 lines identified in an unbiased screen for increased female chasing behavior revealed the involvement of another sexually dimorphic neuron, pC1d, and implicated pC1d and aIPg neurons as core nodes regulating female aggression. pC1d activation increased female aggression and electron microscopy (EM) connectomic analysis demonstrated that aIPg neurons and pC1d have strong reciprocal connections. Our work reveals important regulatory components of the neuronal circuitry that underlies female aggressive social interactions and provides tools for their manipulation.

The neural circuits responsible for animal behavior remain largely unknown. We summarize new methods and present the circuitry of a large fraction of the brain of the fruit fly Drosophila melanogaster. Improved methods include new procedures to prepare, image, align, segment, find synapses in, and proofread such large data sets. We define cell types, refine computational compartments, and provide an exhaustive atlas of cell examples and types, many of them novel. We provide detailed circuits consisting of neurons and their chemical synapses for most of the central brain. We make the data public and simplify access, reducing the effort needed to answer circuit questions, and provide procedures linking the neurons defined by our analysis with genetic reagents. Biologically, we examine distributions of connection strengths, neural motifs on different scales, electrical consequences of compartmentalization, and evidence that maximizing packing density is an important criterion in the evolution of the fly’s brain.

Wiring a complex brain requires many neurons with intricate cell specificity, generated by a limited number of neural stem cells. Drosophila central brain lineages are a predetermined series of neurons, born in a specific order. To understand how lineage identity translates to neuron morphology, we mapped 18 Drosophila central brain lineages. While we found large aggregate differences between lineages, we also discovered shared patterns of morphological diversification. Lineage identity plus Notch-mediated sister fate govern primary neuron trajectories, whereas temporal fate diversifies terminal elaborations. Further, morphological neuron types may arise repeatedly, interspersed with other types. Despite the complexity, related lineages produce similar neuron types in comparable temporal patterns. Different stem cells even yield two identical series of dopaminergic neuron types, but with unrelated sister neurons. Together, these phenomena suggest that straightforward rules drive incredible neuronal complexity, and that large changes in morphology can result from relatively simple fating mechanisms.

Summary Different types of Drosophila dopaminergic neurons (DANs) reinforce memories of unique valence and provide state-dependent motivational control [1]. Prior studies suggest that the compartment architecture of the mushroom body (MB) is the relevant resolution for distinct DAN functions [2, 3]. Here we used a recent electron microscope volume of the fly brain [4] to reconstruct the fine anatomy of individual DANs within three MB compartments. We find the 20 DANs of the γ5 compartment, at least some of which provide reward teaching signals, can be clustered into 5 anatomical subtypes that innervate different regions within γ5. Reconstructing 821 upstream neurons reveals input selectivity, supporting the functional relevance of DAN sub-classification. Only one PAM-γ5 DAN subtype γ5(fb) receives direct recurrent feedback from γ5β′2a mushroom body output neurons (MBONs) and behavioral experiments distinguish a role for these DANs in memory revaluation from those reinforcing sugar memory. Other DAN subtypes receive major, and potentially reinforcing, inputs from putative gustatory interneurons or lateral horn neurons, which can also relay indirect feedback from MBONs. We similarly reconstructed the single aversively reinforcing PPL1-γ1pedc DAN. The γ1pedc DAN inputs mostly differ from those of γ5 DANs and they cluster onto distinct dendritic branches, presumably separating its established roles in aversive reinforcement and appetitive motivation [5, 6]. Tracing also identified neurons that provide broad input to γ5, β′2a, and γ1pedc DANs, suggesting that distributed DAN populations can be coordinately regulated. These connectomic and behavioral analyses therefore reveal further complexity of dopaminergic reinforcement circuits between and within MB compartments., Highlights • Nanoscale anatomy reveals additional subtypes of rewarding dopaminergic neurons • Connectomics reveals input specificity to subtypes of dopaminergic neurons • Axon morphology implies dopaminergic neurons provide subcompartment-level function • Unique dopaminergic subtypes serve aversive memory extinction and sugar learning, Otto et al. use electron microscope resolution connectomics to describe the structure and organization of neurons providing synaptic input to functionally discrete subtypes of dopaminergic neurons. The nanoscale anatomy reveals further anatomical and functional specialization of dopaminergic neurons, which is confirmed with behavioral experiments.

We have investigated the correlations between the in-plane uniaxial magnetic anisotropy (Ku) and spin–orbit torque (SOT) of Ni80Fe20 (Py)/Pt thin films sputtered on a single-crystal 128° Y-Cut LiNbO3 (LNO) substrate by performing second-harmonic voltage measurements. The results show that the value of the damping-like (DL) SOT torque varies with the angle χ between Ku and the applied current and increases with χ from 0° to 90°. The effective spin Hall angle θSH, Pteff = 0.073 and 0.123 for χ = 0 and 90°, respectively, indicate a difference of approximately 1.7 times. The θSH,Pteff at χ = 90° is greater because the direction of the DL-SOT on the magnetization is the same as the Ku direction. This result implies that the effective spin Hall angle can be controlled by the Ku direction of the ferromagnetic metal layer induced on the LNO substrate, thereby providing valuable insight for the development of spin devices using SOT.

Background Image segmentation and registration techniques have enabled biologists to place large amounts of volume data from fluorescence microscopy, morphed three-dimensionally, onto a common spatial frame. Existing tools built on volume visualization pipelines for single channel or red-green-blue (RGB) channels have become inadequate for the new challenges of fluorescence microscopy. For a three-dimensional atlas of the insect nervous system, hundreds of volume channels are rendered simultaneously, whereas fluorescence intensity values from each channel need to be preserved for versatile adjustment and analysis. Although several existing tools have incorporated support of multichannel data using various strategies, the lack of a flexible design has made true many-channel visualization and analysis unavailable. The most common practice for many-channel volume data presentation is still converting and rendering pseudosurfaces, which are inaccurate for both qualitative and quantitative evaluations. Results Here, we present an alternative design strategy that accommodates the visualization and analysis of about 100 volume channels, each of which can be interactively adjusted, selected, and segmented using freehand tools. Our multichannel visualization includes a multilevel streaming pipeline plus a triple-buffer compositing technique. Our method also preserves original fluorescence intensity values on graphics hardware, a crucial feature that allows graphics-processing-unit (GPU)-based processing for interactive data analysis, such as freehand segmentation. We have implemented the design strategies as a thorough restructuring of our original tool, FluoRender. Conclusion The redesign of FluoRender not only maintains the existing multichannel capabilities for a greatly extended number of volume channels, but also enables new analysis functions for many-channel data from emerging biomedical-imaging techniques. Electronic supplementary material The online version of this article (doi:10.1186/s12859-017-1694-9) contains supplementary material, which is available to authorized users.

Wiring a complex brain requires many neurons with intricate cell specificity, generated by a limited number of neural stem cells. Drosophila central brain lineages are a predetermined series of neurons, born in a specific order. To understand how lineage identity translates to neuron morphology, we mapped 18 Drosophila central brain lineages. While we found large aggregate differences between lineages, we also discovered shared patterns of morphological diversification. Lineage identity plus Notch-mediated sister fate govern primary neuron trajectories, whereas temporal fate diversifies terminal elaborations. Further, morphological neuron types may arise repeatedly, interspersed with other types. Despite the complexity, related lineages produce similar neuron types in comparable temporal patterns. Different stem cells even yield two identical series of dopaminergic neuron types, but with unrelated sister neurons. Together, these phenomena suggest that straightforward rules drive incredible neuronal complexity, and that large changes in morphology can result from relatively simple fating mechanisms.

The fruit flyDrosophila melanogasteris an important model organism for neuroscience with a wide array of genetic tools that enable the mapping of individuals neurons and neural subtypes. Brain templates are essential for comparative biological studies because they enable analyzing many individuals in a common reference space. Several central brain templates exist forDrosophila, but every one is either biased, uses sub-optimal tissue preparation, is imaged at low resolution, or does not account for artifacts. No publicly availableDrosophilaventral nerve cord template currently exists. In this work, we created high-resolution templates of theDrosophilabrain and ventral nerve cord using the best-available technologies for imaging, artifact correction, stitching, and template construction using groupwise registration. We evaluated our central brain template against the four most competitive, publicly available brain templates and demonstrate that ours enables more accurate registration with fewer local deformations in shorter time.

The GAL4-UAS system has proven its versatility in studying the function and expression patterns of neurons theDrosophilacentral nervous system. Although the GAL4 system has been used for 25 years, recent genetic intersectional tools have enabled genetic targeting of very small numbers of neurons aiding in the understanding of their function. This split-GAL4 system is extremely powerful for studying neuronal morphology and the neural basis of animal behavior. However, choosing lines to intersect that have overlapping patterns restricted to one to a few neurons has been cumbersome. This challenge is now growing as the collections of GAL4 driver lines has increased. Here we present a new method and software plug-in for Fiji to dramatically improve the speed of querying large databases of potential lines to intersect and aid in the split-GAL4 creation. We also provide pre-computed datasets for the Janelia GAL4 (5,738 lines) and VT GAL4 (7,429 lines) of the Drosophila central nervous system (CNS). The tool reduced our split-GAL4 creation effort dramatically.

This case involved a 64-year-old female patient with a BMI of 35.3 kg/m2 and poorly controlled type 2 diabetes mellitus. Preoperative upper gastrointestinal endoscopy revealed chronic, atrophic gastritis. Helicobacter pylori antibody was negative. The patient underwent laparoscopic sleeve gastrectomy with duodenal-jejunal bypass as a metabolic surgery to treat obesity and type 2 diabetes mellitus. At 1 year postoperatively, routine endoscopy detected a flat elevated lesion at the distal gastric sleeve, near the posterior wall of the antrum; biopsy revealed adenocarcinoma. Endoscopic submucosal resection was performed without complication. This case shows the advantage of laparoscopic sleeve gastrectomy with duodenal-jejunal bypass in screening the excluded stomach as compared to laparoscopic Roux-en-Y gastric bypass. Therefore, laparoscopic sleeve gastrectomy with duodenal-jejunal bypass can be a viable alternative to laparoscopic Roux-en-Y gastric bypass for regions where gastric cancer is endemic.

Stress evaluation in polymeric materials is important in order to not only spot danger in them before serious failure, but also precisely interpret the destructive mechanism, which can improve the lifetime and durability of polymeric materials. Here, we are able to visualize stress by color changes, as well as quantitatively estimate the stress in situ, in segmented polyurethane elastomers with diarylbibenzofuranone-based dynamic covalent mechanophores. We prepared films of the segmented polyurethanes, in which the mechanophores were incorporated in the soft segments, and efficiently activated them by mechanical force. Cleavage of the mechanophores during uniaxial elongation and their recovery after the removal of the stress were quantitatively evaluated by in situ electron paramagnetic resonance measurements, accompanied by drastic color changes.

Background and Aim Helicobacter pylori (H. pylori) infection is a strong risk factor for the development of gastric cancer. In 2013, the Japanese government approved H. pylori eradication therapy in patients with chronic gastritis as well as peptic ulcer. However, the continuing decline in eradication rates for first-line H. pylori eradication therapies is an urgent problem. In this study, we investigated changes in the first-line eradication rate from 2001 to 2010. Methods Eradication rates for 7-day triple therapy [proton pump inhibitor (rabeprazole 20 mg, lansoprazole 60 mg, or omeprazole 40 mg) + amoxicillin 1500 mg + clarithromycin (CAM) 400 or 800 mg, daily] were collated from 14 hospitals in the Tokyo metropolitan area. The urea breath test was used for the evaluation of eradication. The cut-off value was less than 2.5%. Results The yearly eradication rates (intention to treat/per protocol) were 78.5/79.5% (2001, n = 242), 71.2%/72.9% (2002, n = 208), 67.8%/70.5% (2003, n = 183), 75.6%/84.6% (2004, n = 131), 56.4%/70.5% (2005, n = 114), 70.5%/75.8% (2006, n = 271), 67.4%/82.0% (2007,n = 135), 64.0%/76.3% (2008, n = 261), 60.5%/74.3% (2009, n = 329), and 66.5%/78.8% (2010, n = 370), respectively. Examination of eradication rates according to CAM dosage revealed an eradication rate of 65.6% (383/584) for CAM 400 mg daily, and 68.5% (1124/1642) for CAM 800 mg daily, with no significant difference seen between dosages. Conclusion In recent years, eradication rates for first-line triple therapy have obviously decreased, but no noticeable decrease has occurred after 2001.

The brain of fruit fly Drosophila melanogaster has been used as a model system for functional analysis of neuronal circuits, including connectomics research, due to its modest size (~700 μm) and availability of abundant molecular genetics tools for visualizing neurons. Three-dimensional (3D) reconstruction of high-resolution images of neurons or circuits visualized with appropriate methods is a critical step for obtaining information such as morphology and connectivity patterns of neuronal circuits. In this chapter, we introduce methods for generating 3D reconstructed images with data acquired from confocal laser scanning microscopy (CLSM) or electron microscopy (EM) to analyze neuronal circuits found in the central nervous system (CNS) of the fruit fly. Comparisons of different algorithms and strategies for reconstructing neuronal circuits, using actual studies as references, will be discussed within this chapter.

Background: The environment surrounding Helicobacter pylori eradication treatment is dramatically changing. Recently, vonoprazan, a first-in-class potassium-competitive acid blocker (P-CAB), was introduced onto the market in 2015. The aging of Japan’s demographic structure is becoming pronounced. In this study, we examined the trend of the eradication rate of H. pylori in the metropolitan area and examined factors concerning successful eradication. Methods: We collected data from 20 hospitals in the Tokyo metropolitan area on patients who received first-line eradication therapy with a proton-pump inhibitor (PPI)/P-CAB, amoxicillin, and clarithromycin for 1 week and second-line eradication therapy with a PPI/P-CAB, amoxicillin, and metronidazole for 1 week from 2013 to 2018. The annual eradication rate and associated factors for successful eradication were analyzed. Results: We collected data of 4097 and 3572 patients in the first- and second-line eradication therapies, respectively. The eradication rate decreased from 2013 to 2014 and increased again from 2015 to 2018 with the first-line therapy [the eradication rates in 2013, 2014, 2015, 2016, 2017 and 2018 were 71.8%, 63.7%, 78.5%, 84.6%, 89.7 and 90.1%, respectively, in the per protocol (PP)]. The second-line eradication rates were 90.0%, 82.6%, 88.8%, 87.5%, 91.8% and 90.1% in 2013, 2014, 2015, 2016, 2017 and 2018, respectively, in PP. Vonoprazan was an independent factor for successful eradication in not only first-line, but also second-line eradication. Age over 75 years was an independent factor for eradication failure in both first- and second-line eradication therapies. Conclusion: The eradication rate improved from 2015 to 2018 with the first-line therapy because of the introduction of vonoprazan in the market. The eradication rates with first- and second-line regimens in elderly patients were lower than those in younger patients.

In this work, we describe a process to synthesize novel liquid–crystalline (LC) benzoxazines from a LC phenol that contains biphenyl, ester and azomethine groups in the mesogenic moiety, various alkyl amines and formaldehyde. The LC behavior of the biphenyl-containing benzoxazines was investigated by differential scanning calorimetry and polarized optical microscopy and compared with analogous phenyl-containing LC benzoxazines containing phenyl, ester and azomethine groups in the mesogenic moiety. While the LC benzoxazines containing the phenyl groups only exhibited a nematic phase upon heating, the LC benzoxazines containing biphenyl groups exhibited a smectic phase as well as a nematic phase. Additionally, the LC-isotropic transition temperatures were over 100 °C higher than that for the phenyl-containing LC benzoxazines. A film obtained by curing the biphenyl-containing LC benzoxazine at 180 °C for 1 h exhibited birefringence. Finally, the thermal diffusivity of the cured LC benzoxazines was also investigated.

Background In Japan, the eradication rate of first-line therapy for Helicobacter pylori (H. pylori) with a proton pump inhibitor (PPI), amoxicillin (AMPC) and clarithromycin (CAM) has been decreasing because of a high prevalence of CAM resistance. A possible decrease of the eradication rate for second-line therapy with a PPI, AMPC and metronidazole (MNZ) is of concern. The aim of this study is to assess the trends in second-line eradication therapy for H. pylori in Japan. Materials and Methods We accumulated data retrospectively on patients administered second-line eradication therapy for Helicobacter pylori with a PPI, AMPC, and MNZ for 1 week after failure of first-line eradication therapy with a PPI, AMPC and CAM at 15 facilities in the Tokyo metropolitan area in Japan from 2007 to 2011. Trends for second-line eradication rates in modified intention-to-treat (ITT) analyses were investigated. Second-line eradication rates were categorized by three PPIs (rabeprazole (RPZ), lansoprazole (LPZ) or omeprazole (OMZ)) and evaluated. Results We accumulated data on 1373 patients. The overall second-line eradication rate was 92.4%. Second-line eradication rates in 2007, 2008, 2009, 2010 and 2011 were 97.7, 90.6, 94.5, 91.8 and 91.8%, respectively, with no significant trends revealed. Second-line eradication rates categorized by three PPIs for the entire 5-year period were 91.6, 93.4 and 92.4% (RPZ, LPZ and OPZ, respectively) with no significant differences among the three PPIs. Conclusions From 2007 to 2011, there were no significant trends in the second-line eradication rates and the rates remained consistently high. From the viewpoint of high prevalence of CAM resistance in Japan, triple therapy with PPI, AMPC and MNZ may be a better strategy for first-line therapy compared to triple therapy with PPI, AMPC and CAM.