Suzuki S, Kanno T, Koike T, Chiba T, Asanuma K, Kato K, Hatayama Y, Ogata Y, Saito M, Hatta W, Uno K, Imatani A, Masamune A. Epidemiology of dyspepsia and esophagogastroduodenoscopic findings in the era of Helicobacter pylori eradication. World J Gastroenterol 2025; 31(37): 110942 [DOI: 10.3748/wjg.v31.i37.110942]
Corresponding Author of This Article
Takeshi Kanno, MD, PhD, Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 9808575, Miyagi, Japan. kanno.takeshi@med.tohoku.ac.jp
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Observational Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Suguo Suzuki, Takeshi Kanno, Tomoyuki Koike, Yutaka Hatayama, Yohei Ogata, Masahiro Saito, Waku Hatta, Kaname Uno, Akira Imatani, Atsushi Masamune, Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 9808575, Miyagi, Japan
Takeshi Kanno, Research and Development Division of Career Education for Medical Professionals, Medical Education Center, Jichi Medical University, Shimotsuke 3290498, Tochigi, Japan
Takashi Chiba, Kiyotaka Asanuma, Katsuaki Kato, Cancer Screening Center, Miyagi Cancer Society, Sendai 9800011, Miyagi, Japan
Author contributions: Suzuki S, Kanno T, and Koike T contributed to conceptualization; Suzuki S and Kanno T contributed to methodology and writing - original draft preparation; Suzuki S, Kanno T, and Chiba T contributed to formal analysis and investigation; Koike T, Chiba T, Asanuma K, Kato K, Hatayama Y, Ogata Y, Saito M, Hatta W, Uno K, Imatani A, and Masamune A contributed to writing - review and editing; Koike T and Masamune A contributed to supervision.
Institutional review board statement: This study was conducted according to the principles of the Declaration of Helsinki (as revised in Brazil in 2013) and approved by the Ethics Committees of the Miyagi Cancer Society (Approval No. 3-2206).
Informed consent statement: Written informed consent was not obtained, as the study involved the secondary use of anonymized data collected through a municipal gastric cancer screening program. Personal identifiers were removed before analysis. Information regarding the study was made publicly available on the institutional website, and an opt-out option was provided to protect participants’ rights.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: Due to the nature of this research, participants of this study did not agree for their data to be shared publicly, so supporting data is not available.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Takeshi Kanno, MD, PhD, Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 9808575, Miyagi, Japan. kanno.takeshi@med.tohoku.ac.jp
Received: June 24, 2025 Revised: July 23, 2025 Accepted: August 25, 2025 Published online: October 7, 2025 Processing time: 96 Days and 2.3 Hours
Abstract
BACKGROUND
Since Japanese national insurance coverage was expanded to include Helicobacter pylori (H. pylori) gastritis in 2013, approximately 1.5 million patients have received eradication therapy annually. However, the prevalence and clinical features of uninvestigated dyspepsia in the post-eradication era remain unclear.
AIM
To evaluate the prevalence of dyspepsia and related endoscopic findings in the general population.
METHODS
We analyzed data from a gastric cancer screening program using esophagogastroduodenoscopy in Sendai city between 2019 and 2021. Data regarding endoscopic findings, upper gastrointestinal symptoms, and history of H. pylori eradication were collected. Dyspepsia was defined as the presence of upper abdominal pain, bloating, or both. Multivariate logistic regression was used to identify independent factors associated with dyspepsia.
RESULTS
Among 23250 participants, overall dyspepsia prevalence was 28.0%. It was 28.7% in the non-infected and post-eradication cohorts, and lower (25.8%, P < 0.05) in the currently infected or naturally eradicated cohort. In addition, 23.1% of participants reported heartburn. The following were independently associated with dyspepsia: Age < 60 years, female sex, gastric ulcers, duodenal ulcers, erosive esophagitis, a history of gastric surgery, and successful H. pylori eradication. Gastric or esophageal cancer showed no association.
CONCLUSION
Uninvestigated dyspepsia remains common even after successful H. pylori eradication. Dyspepsia was not considered a reliable indicator of gastric or esophageal cancer.
Core Tip: We analyzed over 23000 adults undergoing endoscopic gastric cancer screening in Japan to assess dyspepsia prevalence across Helicobacter pylori infection statuses. Dyspepsia was most prevalent (28.7%) in the post-eradication and non-infected groups, compared to 25.8% in the currently infected group. Younger age, female sex, peptic ulcers, erosive esophagitis, and post-eradication status were independently associated with dyspepsia. Despite extensive endoscopic evaluation, over 90% of cases had no organic findings. These results highlight the evolving nature of dyspepsia and its persistence in the post-Helicobacter pylori era.
Citation: Suzuki S, Kanno T, Koike T, Chiba T, Asanuma K, Kato K, Hatayama Y, Ogata Y, Saito M, Hatta W, Uno K, Imatani A, Masamune A. Epidemiology of dyspepsia and esophagogastroduodenoscopic findings in the era of Helicobacter pylori eradication. World J Gastroenterol 2025; 31(37): 110942
Dyspepsia, a prevalent gastrointestinal disorder, is characterized by abdominal pain, indigestion, epigastric discomfort, bloating, and nausea[1,2]. Patients with this condition usually experience impaired quality of life, highlighting its clinical and economic significance. Previous systematic reviews have shown that approximately 10%-20% of individuals undergoing health checkups in Japan experience chronic epigastric symptoms[3-5]. Similarly, the pooled global prevalence of dyspepsia is 20%[6]. Dyspepsia occurs in association with organic diseases, such as peptic ulcers, and in cases where no organic cause is identified. Notably, 85% of patients with dyspepsia who undergo upper gastrointestinal endoscopy have normal endoscopic findings[2,7-9]. Even in cases of functional dyspepsia without organic diseases, patients incur substantial costs, and work productivity is impaired owing to dyspeptic symptoms[10-12]. The annual direct cost to patients is 699 dollars, with an estimated 1.4 hours of work lost per week owing to functional dyspepsia symptoms[13]. Helicobacter pylori (H. pylori) infection is associated with dyspepsia, and symptom improvement is observed in some patients after eradication[14]. However, the prevalence of dyspeptic symptoms in patients after successful H. pylori eradication remains partially studied.
In Japan, clinical practice guidelines for dyspepsia recommend considering eradication therapy as the first-line treatment for all H. pylori-positive cases[15,16]. Furthermore, Japan introduced national insurance coverage for eradication therapy for all patients with H. pylori infections in 2013. This policy was implemented to support gastric cancer prevention and address the historically high infection rate. Moreover, approximately 1.5 million patients undergo eradication therapy annually[17]. Thus, substantial societal changes have led to a growing post-eradication population. Despite this shift, no large-scale epidemiological studies have been conducted in Japan over the past two decades to assess the prevalence of undiagnosed dyspepsia, associated endoscopic findings, or H. pylori infection status. Owing to the historically high incidence of gastric cancer in Japan, national screening programs have been long established. A gradual shift from radiography-based to endoscopic screening has been observed recently. The population of Sendai city is approximately 1060000, with 500000 residents aged ≥ 49 years[18]. Within this framework, the Sendai city endoscopic gastric cancer screening project, initiated in 2019, targets this population. Eligible individuals are encouraged to undergo screening every 2 years. We aim to clarify the epidemiology of dyspepsia in the general population, considering the H. pylori infection status and esophagogastroduodenoscopic (EGD) findings.
MATERIALS AND METHODS
Ethical approval and informed consent
This study was conducted according to the principles of the Declaration of Helsinki (as revised in Brazil in 2013), STROBE reporting guidelines, and approved by the Ethics Committees of the Miyagi Cancer Society (Approval No. 3-2206). Written informed consent was not obtained, as the study involved the secondary use of anonymized data collected through a municipal gastric cancer screening program. Personal identifiers were removed before analysis. The study information was made publicly available on the institutional website, and an opt-out option was provided to protect participants’ rights.
Study population
In this cross-sectional study, we used data from the municipal gastric cancer screening program in Sendai city, targeting residents aged ≥ 49 years, conducted between June 27, 2019 and February 27, 2021. A total of 23250 participants were included, with no duplicate cases during the 2 years. Eligible participants selected one of the registered medical institutions for EGD and underwent the procedure after completing a medical questionnaire.
Medical questionnaire
As part of the health screening program, participants completed a medical questionnaire before undergoing EGDs. The questionnaire included information on H. pylori eradication, screening tests for H. pylori, use of antithrombotic agents, and gastrointestinal symptoms, such as heartburn, upper abdominal pain, and bloating. Additionally, data on sex and age were obtained. Information on H. pylori eradication history was collected via a self-reported questionnaire, including the timing of eradication, the presence or absence of eradication confirmation, and the medical facility where the test was performed. These data were subjected to a double-check by public health nurses and trained nurses to ensure accuracy. All data were anonymized, and each participant was assigned an independent study number before data collection. Dyspepsia was defined as the presence of upper abdominal pain, bloating, or both. Incomplete responses on the questionnaires were considered missing values.
EGD: Outline of the procedure
Only pre-registered endoscopists were authorized to perform EGD for the gastric cancer screening program. First, a preliminary report was prepared by a local endoscopist, and biopsies were performed at the physician’s discretion. Histopathological results, preliminary reports, and EGD images were submitted to the relevant cancer society. A secondary review was conducted by an independent expert endoscopist, who evaluated the EGD images and histopathological results of the biopsies in reference to the preliminary reports, to provide a final diagnostic evaluation. Gastric atrophy was evaluated according to the Kimura-Takemoto classification, with atrophy defined as extension to C-2 or beyond, based on the endoscopic findings. Malignancy was defined according to histopathological diagnosis rather than endoscopic appearance. For this study, anonymized data from the final reports, identified by research-specific study identification numbers, were used. Terminologies within the reports were standardized to ensure the consistent documentation of gastric atrophy and history of gastric surgery.
Classification of the H. pylori infection status
Participants were categorized into three cohorts based on their self-reported H. pylori eradication history and the presence or absence of endoscopic gastric atrophy. Those with a history of successful eradication were assigned to the post-eradication cohort. Participants without a history of eradication or endoscopic evidence of atrophy were classified as non-infected. Furthermore, participants without a history of eradication but with endoscopic evidence of gastric atrophy were classified as currently infected or having had H. pylori naturally eradicated.
Statistical analysis
Data have been presented as numbers and percentages. Nominal variables were analyzed using Fisher’s exact test. The Kruskal-Wallis test was applied to compare ≥ three groups of sample data. To identify factors correlated with dyspepsia, we compared the demographic and clinical characteristics of participants with and without the condition. Variables with potential correlations were subsequently included in a multivariate logistic regression model to determine independent factors. All statistical analyses were performed using EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan), a graphical user interface for R (R Foundation for Statistical Computing, Vienna, Austria). EZR is a modified version of R Commander (Department of Informatics, Yokohama National University, Yokohama, Japan) enhanced to incorporate statistical functions frequently used in biostatistics[19]. Statistical significance was set at P < 0.05.
RESULTS
Background characteristics of participants
A total of 23250 participants participated in the screening, including 9562 males (41.1%) and 13688 females (58.9%), with a mean age of 69.1 ± 8.5 years. Regarding self-reported upper gastrointestinal symptoms, 4810 (20.7%), 2580 (11.1%), and 5380 (23.1%) participants reported heartburn, upper abdominal pain, and bloating, respectively. Based on symptom responses, 6499 participants (28.0%) were classified as having dyspepsia, defined as the presence of upper abdominal pain, bloating, or both (Table 1).
Table 1 Background characteristics of the participants, n (%).
Figure 1 presents the prevalence of upper gastrointestinal symptoms by age cohort. The prevalence of heartburn remained relatively stable at approximately 20% across all age cohorts. In contrast, the prevalence of upper abdominal pain declined markedly after the age of 60 years, decreasing from 15.9% in participants aged 49-59 years to 10.9% in those aged 60-69 years. Similarly, the prevalence of bloating decreased progressively with age, from 26.9% in participants aged < 60 years to 20.3% in those aged ≥ 80 years. These trends imply that the overall prevalence of dyspepsia was higher among participants aged < 60 years (33.5%) than among those aged ≥ 60 years (27.0%, P < 0.001).
Figure 1 Prevalence rates of upper gastrointestinal symptoms.
A: Prevalence of upper gastrointestinal symptoms, including heartburn, upper abdominal pain and bloating, and dyspepsia by 10-year age groups and in the overall population. The prevalence of upper abdominal pain declines after the age of 60 years, while bloating gradually decreases with advancing age; B: Comparison of dyspepsia prevalence between participants younger than 60 years and those aged ≥ 60 years. Dyspepsia is statistically significantly more prevalent in participants aged < 60 years than in those aged ≥ 60 years (Fisher’s exact test: aP < 0.001).
EGD findings
Of the 23250 participants who underwent EGD, 91 (0.4%), 29 (0.1%), and 1240 (5.3%) were diagnosed with gastric ulcers, duodenal ulcers, or reflux esophagitis (Los Angeles classification grade A or more severe), respectively. Moreover, esophageal cancer, gastric cancer, or a history of gastric surgery were identified in 27 (0.1%), 180 (0.8%), and 277 (1.2%) participants, respectively. Overall, 92.3% of participants had no organic findings on EGD (Table 2). The gastric atrophy status was assessed based on a combination of endoscopic findings and a history of H. pylori eradication. Among the participants, 31.9% had non-eradicated atrophic gastritis, 29.5% exhibited atrophic changes post-eradication, and 38.6% showed no atrophic changes.
Table 2 Esophagogastroduodenoscopic findings, n (%).
Prevalence of dyspepsia by the H. pylori infection status
The prevalence of dyspepsia was compared across three cohorts, defined by H. pylori eradication history and the endoscopic atrophic status (Figure 2). Dyspepsia prevalence was 28.7% in the non-infected and post-eradication cohorts, with no notable differences between the two cohorts. In contrast, the currently infected/naturally eradicated cohort had a lower prevalence (25.8%) than did the other two cohorts (P < 0.01 and P < 0.05, respectively).
Figure 2 Prevalence of dyspepsia according to the Helicobacter pylori status and gastric atrophy.
The prevalence of dyspepsia across the three cohorts categorized by Helicobacter pylori (H. pylori) eradication history and endoscopic evidence of atrophic gastritis is presented. Dyspepsia prevalence is 28.7% in the non-infected and post-eradication cohorts, with no marked difference. The currently infected/naturally eradicated cohort has a prevalence (25.8%) lower than that of the other two cohorts (Kruskal-Wallis test: aP < 0.05 and bP < 0.01, respectively). The “currently infected or naturally eradicated” cohort includes individuals without a self-reported H. pylori eradication history but with endoscopic gastric atrophy, representing a heterogeneous group where active H. pylori infection cannot be precisely distinguished from a few spontaneous eradications due to the absence of additional infection testing. NS: Not significant.
Factors correlated with dyspepsia
Baseline characteristics were compared between participants with and without dyspepsia (Table 3). Statistically significant differences were observed in age, sex, and the prevalence of duodenal ulcer, reflux esophagitis, gastric cancer, and non-eradicated atrophic gastritis between these two sub-cohorts. Based on these variables, a multivariate logistic regression analysis was conducted to identify the independent factors correlated with dyspepsia (Figure 3). The analysis revealed that the following factors were independently correlated with dyspepsia: Age < 60 years [odds ratio (OR) = 1.25; 95% confidence interval (CI): 1.15-1.35], female sex (OR = 1.81; 95%CI: 1.70-1.93), successful H. pylori eradication (OR = 1.14; 95%CI: 1.07-1.21), gastric ulcer (OR = 1.57; 95%CI: 1.01-2.44), duodenal ulcer (OR = 2.51; 95%CI: 1.20-5.26), reflux esophagitis (OR = 1.31; 95%CI: 1.16-1.49), and a history of gastric surgery (OR = 1.57; 95%CI: 1.21-2.03). Conversely, no notable correlations were found for gastric or esophageal cancer.
Figure 3 Multivariate logistic regression analysis of factors correlated with dyspepsia.
This analysis revealed that the following factors were independently correlated with dyspepsia: Age < 60 years [odds ratio (OR) = 1.25; 95% confidence interval (CI): 1.15-1.35], female sex (OR = 1.81; 95%CI: 1.70-1.93), successful Helicobacter pylori eradication (OR = 1.14; 95%CI: 1.07-1.21), gastric ulcer (OR = 1.57; 95%CI: 1.01-2.44), duodenal ulcer (OR = 2.51; 95%CI: 1.20-5.26), reflux esophagitis (OR = 1.31; 95%CI: 1.16-1.49), and history of gastric surgery (OR = 1.57; 95%CI: 1.21-2.03). Conversely, no notable correlations were found for gastric or esophageal cancer. H. pylori: Helicobacter pylori; Los A: Los Angeles classification grade A reflux esophagitis; OR: Odds ratio.
Table 3 Comparative analysis of dyspepsia-positive and -negative cohorts, n (%).
This study provides epidemiological insights into uninvestigated dyspepsia and upper gastrointestinal symptoms in the general population through the data derived from a large-scale endoscopic gastric cancer screening program. Previous epidemiological studies have consistently demonstrated that the prevalence of dyspepsia differs markedly between the general and hospital-based populations, with clinical populations typically exhibiting higher prevalence rates[3-5]. Thus, this large population-based study of over 23000 adults aged ≥ 49 years offers valuable epidemiological insights that differ from those obtained from clinical settings. A major strength of this study is the integration of detailed endoscopic findings with the H. pylori eradication status. This approach offers a multifaceted perspective on the prevalence and clinical significance of dyspeptic symptoms in contemporary Japan, where a substantial proportion of the population has undergone successful eradication.
First, we observed a dyspepsia prevalence of 28% in the general population, substantially higher than the previously reported range of 11%-17% in a similar population two decades ago[3-5,20]. Importantly, this study investigated the prevalence and background of uninvestigated dyspepsia, encompassing individuals with organic diseases, rather than functional dyspepsia as defined by Rome IV criteria[21]. Owing to Japan’s ethnic homogeneity and relatively stable sociocultural conditions, this increase in uninvestigated dyspepsia may reflect physiological changes within the population. One possible explanation is the increasing proportion of individuals with normal gastric acid secretion. This includes individuals who are H. pylori-negative and those who experience post-eradication recovery of acid secretion. Iijima et al[22] have observed an increase in gastric acid secretion in Japan over recent decades, primarily attributed to the declining prevalence of H. pylori infection. In this study, approximately 68% of participants showed no endoscopic evidence of gastric atrophy or had a history of successful eradication therapy. Regarding the correlation between the H. pylori infection status and dyspepsia, symptom prevalence was identical (28.7%) in the non-infected and post-eradication cohorts. This was notably higher than that in participants presumed to be currently infected or who had undergone natural eradication (25.8%). While eradication therapy for H. pylori infection improves dyspeptic symptoms, meta-analyses have indicated that the number needed for treatment remains modest: 9 (95%CI: 7-17) for partial symptom improvement and 14 (95%CI: 11-21) for complete symptom resolution[12]. Despite these benefits, the prevalence of dyspepsia in post-eradication populations remains partially studied. These findings offer significant new insights into the substantial proportion of patients who continue to experience dyspepsia despite successful eradication therapy. Additionally, while approximately 20% of the participants reported heartburn, only 5% exhibited endoscopic evidence of reflux esophagitis. This discrepancy highlights the epidemiological gap between reflux symptoms and organic diseases in the general Japanese population.
Second, our findings confirmed that most participants with dyspepsia (92.3%) had no clinically significant organic findings on EGD. This outcome aligns with the results of previous studies indicating that approximately 85% of patients with dyspepsia have negative endoscopic findings[2]. Multivariate logistic regression analysis revealed younger age, female sex, the presence of gastric or duodenal ulcers or erosive esophagitis, and a history of gastric surgery as independent factors correlated with dyspepsia, consistent with previous findings[23,24]. Conversely, gastric and esophageal cancers were not considerably correlated with dyspeptic symptoms. Advanced cancers may present with prominent symptoms, such as obstruction, bleeding, or nutritional deficiencies, which could contribute to dyspeptic complaints. However, such findings are uncommon in population-based health screenings. In this context, malignancies are frequently detected at an early stage, which may explain the lack of correlation with symptoms. This observation aligns with those of previous epidemiological studies in the general population, which have shown a limited association between dyspepsia and gastrointestinal malignancies[7]. These findings validate the limited utility of dyspepsia as a predictor of malignancy.
This study had some limitations. Firstly, H. pylori infection status was primarily determined using a self-reported questionnaire rather than systematic chemical or histopathological tests. While this approach is common in large-scale epidemiological studies, it inherently posed a limitation regarding precise diagnostic confirmation. However, we considered the self-reported data in our cohort to possess a considerable degree of reliability. A recent report demonstrated high reliability of such questionnaires for epidemiological investigations of H. pylori eradication, showing substantial agreement with medical records[25]. Furthermore, as detailed in the methods section, the self-reported eradication information in this study was meticulously verified through a double-check process conducted by public health nurses and trained nurses. Despite these efforts to enhance reliability, it was not possible to precisely identify individuals with active infection within the group showing endoscopic atrophy but no reported eradication history. This cohort likely included a majority of actively infected individuals, but may also have encompassed a subset with spontaneously cleared infection or unintended eradication due to prior antibiotic use. This inherent characteristic of the dataset should be considered when interpreting our findings. According to a meta-analysis, the rate of reinfection after the successful eradication of H. pylori is approximately 19% in regions with underdeveloped water and sanitation systems[26]. In contrast, Japan, with its nearly universal tap water infrastructure and reduced use of well water, reported a reinfection rate of only 0.2% in a 2012 study population of over 1600 participants, indicating a low likelihood of reinfection[27]. Second, our questionnaire did not fully encompass all symptoms defined by international diagnostic criteria for functional dyspepsia, such as postprandial fullness and early satiety[21]. This simplification might have led to an underestimation of the true prevalence of dyspepsia. While this symptom-based approach was pragmatic for a large-scale health screening and aligned with our objective of broadly understanding epidemiological trends without imposing strict clinical background limitations, we acknowledge that our analysis focused solely on self-reported upper abdominal symptoms and did not differentiate potential underlying non-gastrointestinal causes of abdominal pain, such as biliary or pancreatic diseases. Thus, some reported symptoms may have originated from sources beyond the gastrointestinal tract, which should be considered when interpreting the overall prevalence of dyspepsia. Finally, the questionnaire did not collect data on the use of medications known to influence gastrointestinal symptoms, including acid suppressive agents and nonsteroidal anti-inflammatory drugs. The absence of these variables limited our ability to control for important confounders in the multivariate analysis, and their use could have influenced the observed prevalence and associations of dyspepsia and EGD findings.
CONCLUSION
Dyspepsia was prevalent in 28.0% of the adult Japanese population. The post-eradication cohort reported a dyspepsia prevalence of 28.7%, the same as in the non-infected group. Similarly, dyspepsia was correlated with age, the female sex, successful H. pylori eradication, erosive esophagitis, gastric and duodenal ulcers, and a history of gastric surgery.
Footnotes
Provenance and peer review: Invited article; Externally peer reviewed.
Peer-review model: Single blind
Corresponding author’s membership in professional societies: The Japanese Society of Gastroenterology; Canadian Association of Gastroenterology.
Specialty type: Gastroenterology and hepatology
Country of origin: Japan
Peer-review report’s classification
Scientific Quality: Grade B, Grade B, Grade B
Novelty: Grade B, Grade B, Grade B
Creativity or Innovation: Grade B, Grade B, Grade B
Scientific Significance: Grade B, Grade B, Grade B
P-Reviewer: Rao RSP, PhD, Professor, India; Wang C, PhD, China S-Editor: Zuo Q L-Editor: A P-Editor: Lei YY
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