1.Belching and Reflux: The Relationship and the Underlying Mechanism
Songfeng CHEN ; Xingyu JIA ; Dianxuan JIANG ; Mengyu ZHANG ; Niandi TAN ; Qianjun ZHUANG ; Yinglian XIAO
Journal of Neurogastroenterology and Motility 2026;32(2):254-256
Background/Aims:
Belching can occur either independently or concurrently with reflux symptoms. This study aims to explore the relationship between belching and reflux and explore the underlying mechanisms involved.
Methods:
Firstly, patients with isolated belching symptoms or concurrent belching and reflux symptoms were retrospectively enrolled. High-resolution esophageal impedance manometry (HRIM) and 24-hour pH impedance monitoring were used to assess belching types and temporal relationship between belching and reflux. Secondly, subjects with belching disorder were prospectively recruited. Postprandial HRIM monitoring was used to clarify the relationship and underlying mechanisms between belching and reflux.
Results:
In the initial phase, 139 subjects were enrolled. Regardless of patients' symptom spectrum (with or without gastroesophageal reflux symptoms), the proportion of preceding-reflux belching was significantly higher in those with objective evidence of gastroesophageal reflux disease, compared to those without (both P < 0.05), which indicated that belching could trigger reflux events and led to more severe reflux burden. To clarify the potential mechanisms involved, 44 belching subjects were prospectively enrolled in the second phase of this study. HRIM analysis demonstrated that maximum intragastric pressure, gastric–lower esophageal sphincter pressure gradient and gastric–esophageal pressure gradient were significantly higher in preceding-reflux belching than those in independent belching.
Conclusions
This study demonstrated that belching might trigger reflux by increasing intragastric pressure, elevating the gastric-sphincter pressure gradient, which enables gastric contents to pass through the esophagogastric junction.These findings have crucial clinical significance, suggesting that reducing the occurrence of belching might be a potential treatment for refractory reflux.
2.Overlapping Reflux Symptoms in Functional Dyspepsia Are Mostly Unrelated to Gastroesophageal Reflux
Songfeng CHEN ; Xingyu JIA ; Qianjun ZHUANG ; Xun HOU ; Kewin T H SIAH ; Mengyu ZHANG ; Fangfei CHEN ; Niandi TAN ; Junnan HU ; Yinglian XIAO
Journal of Neurogastroenterology and Motility 2025;31(2):218-226
Background/Aims:
Reflux symptoms frequently present in patients diagnosed with functional dyspepsia (FD). This investigation sought to elucidate the contribution of gastroesophageal reflux in the overlap relationship.
Methods:
Consecutive patients presenting with reflux symptoms and/or FD symptoms were prospectively included. Comprehensive assessments, including symptoms evaluation, endoscopy, esophageal functional examinations (high-resolution manometry and reflux monitoring), and proton pump inhibitor (PPI) treatment efficacy evaluation, were conducted in these patients.
Results:
The study enrolled 315 patients, 43.2% of which had concurrent FD symptoms and overlapping reflux symptoms. Notably, a mere 28.7% of patients in the overlap symptoms group had objective gastroesophageal reflux disease evidences (the grade of esophagitis≥ B or the acid exposure time ≥ 4.2%). Functional heartburn was demonstrated to be the main cause of overlapping reflux symptoms(55.1%). Reflux parameters analysis revealed that the reflux burden in the overlap symptoms group paralleled that of the FD symptoms group, with both registering lower levels than the reflux symptoms group (P < 0.05). Furthermore, PPI response rates were notably diminished in the overlap symptoms group (P < 0.001), even for those with objective gastroesophageal reflux disease evidences.
Conclusions
The study illuminated that overlapping reflux symptoms in FD was common. Strikingly, these symptoms primarily diverged from reflux etiology and exhibited suboptimal responses to PPI intervention. These findings challenge prevailing paradigms and accentuate the imperative for nuanced therapeutic approaches tailored to the distinctive characteristics of overlapping reflux symptoms in the context of FD.
3.Overlapping Reflux Symptoms in Functional Dyspepsia Are Mostly Unrelated to Gastroesophageal Reflux
Songfeng CHEN ; Xingyu JIA ; Qianjun ZHUANG ; Xun HOU ; Kewin T H SIAH ; Mengyu ZHANG ; Fangfei CHEN ; Niandi TAN ; Junnan HU ; Yinglian XIAO
Journal of Neurogastroenterology and Motility 2025;31(2):218-226
Background/Aims:
Reflux symptoms frequently present in patients diagnosed with functional dyspepsia (FD). This investigation sought to elucidate the contribution of gastroesophageal reflux in the overlap relationship.
Methods:
Consecutive patients presenting with reflux symptoms and/or FD symptoms were prospectively included. Comprehensive assessments, including symptoms evaluation, endoscopy, esophageal functional examinations (high-resolution manometry and reflux monitoring), and proton pump inhibitor (PPI) treatment efficacy evaluation, were conducted in these patients.
Results:
The study enrolled 315 patients, 43.2% of which had concurrent FD symptoms and overlapping reflux symptoms. Notably, a mere 28.7% of patients in the overlap symptoms group had objective gastroesophageal reflux disease evidences (the grade of esophagitis≥ B or the acid exposure time ≥ 4.2%). Functional heartburn was demonstrated to be the main cause of overlapping reflux symptoms(55.1%). Reflux parameters analysis revealed that the reflux burden in the overlap symptoms group paralleled that of the FD symptoms group, with both registering lower levels than the reflux symptoms group (P < 0.05). Furthermore, PPI response rates were notably diminished in the overlap symptoms group (P < 0.001), even for those with objective gastroesophageal reflux disease evidences.
Conclusions
The study illuminated that overlapping reflux symptoms in FD was common. Strikingly, these symptoms primarily diverged from reflux etiology and exhibited suboptimal responses to PPI intervention. These findings challenge prevailing paradigms and accentuate the imperative for nuanced therapeutic approaches tailored to the distinctive characteristics of overlapping reflux symptoms in the context of FD.
4.Overlapping Reflux Symptoms in Functional Dyspepsia Are Mostly Unrelated to Gastroesophageal Reflux
Songfeng CHEN ; Xingyu JIA ; Qianjun ZHUANG ; Xun HOU ; Kewin T H SIAH ; Mengyu ZHANG ; Fangfei CHEN ; Niandi TAN ; Junnan HU ; Yinglian XIAO
Journal of Neurogastroenterology and Motility 2025;31(2):218-226
Background/Aims:
Reflux symptoms frequently present in patients diagnosed with functional dyspepsia (FD). This investigation sought to elucidate the contribution of gastroesophageal reflux in the overlap relationship.
Methods:
Consecutive patients presenting with reflux symptoms and/or FD symptoms were prospectively included. Comprehensive assessments, including symptoms evaluation, endoscopy, esophageal functional examinations (high-resolution manometry and reflux monitoring), and proton pump inhibitor (PPI) treatment efficacy evaluation, were conducted in these patients.
Results:
The study enrolled 315 patients, 43.2% of which had concurrent FD symptoms and overlapping reflux symptoms. Notably, a mere 28.7% of patients in the overlap symptoms group had objective gastroesophageal reflux disease evidences (the grade of esophagitis≥ B or the acid exposure time ≥ 4.2%). Functional heartburn was demonstrated to be the main cause of overlapping reflux symptoms(55.1%). Reflux parameters analysis revealed that the reflux burden in the overlap symptoms group paralleled that of the FD symptoms group, with both registering lower levels than the reflux symptoms group (P < 0.05). Furthermore, PPI response rates were notably diminished in the overlap symptoms group (P < 0.001), even for those with objective gastroesophageal reflux disease evidences.
Conclusions
The study illuminated that overlapping reflux symptoms in FD was common. Strikingly, these symptoms primarily diverged from reflux etiology and exhibited suboptimal responses to PPI intervention. These findings challenge prevailing paradigms and accentuate the imperative for nuanced therapeutic approaches tailored to the distinctive characteristics of overlapping reflux symptoms in the context of FD.
5.A survey on the current knowledge of small intestinal bacterial overgrowth among Chinese gastroenterology clinicians
Mengyu ZHANG ; Fangfei CHEN ; Niandi TAN ; Yinglian XIAO
Chinese Journal of Digestion 2025;45(8):541-547
Objective:To investigate the current level of awareness among Chinese gastroenterologists regarding small intestinal bacterial overgrowth (SIBO).Methods:From March 7th to April 14th, 2024, an online survey questionnaire was sent to qualified clinical physicians specializing in gastroenterology in various levels of general hospitals across the country through the official channels of national academic organizations such as the Gastroenterology Branch of the Chinese Medical Association, the Gastrointestinal Motility Group of the Gastroenterology Branch of the Chinese Medical Association, and the Functional Gastrointestinal Disorders Collaborative Group of the Gastroenterology Branch of the Chinese Medical Association, as well as through the national medical continuing education project cooperation platform. The questionnaire content includes basic information, awareness of consensus guidelines on functional gastrointestinal disorders (FGID) and SIBO, understanding of SIBO and its diagnosis and treatment strategies, et al. The influencing factors of physicians′ cognitive level regarding SIBO were analyzed based on the questionnaire results. Statistical methods employed descriptive statistical method and partial correlation analysis.Results:A total of 511 valid questionnaires were collected, among them, 78.1% (399/511) of the respondents practiced in tertiary hospitals, and 90.2% (461/511) of the respondents were aware of the definition of SIBO. However, only 9.0% (46/511) could accurately identify all the key points of the relevant consensus guidelines. Educational background (undergraduate and master′s degree vs. doctor degree, OR=0.265, 0.528, 95% confidence interval(95% CI): 0.155 to 0.454, 0.322 to 0.865), professional title (junior title vs. senior title, OR=0.577, 95% CI: 0.344 to 0.968), and the number of SIBO cases handled per year (less than 50 cases vs. more than 200 cases, OR=0.144, 95% CI: 0.043 to 0.479) were independent influencing factors that affect the cognitive level of specialist physicians regarding SIBO and the guidelines (all P<0.05). The results of hydrogen and methane breath test (HMBT) was the main reference indicator for diagnosing SIBO in the respondents (79.8%, 408/511), but only 8.4%(43/511) of the specialists were familiar with the principle of HMBT, and 65.9% (337/511) were not clear about the differences in diagnostic thresholds among different consensus or guidelines. Rifaximin was the most commonly used therapy (87.5%, 447/511), but there was significant heterogeneity in the selection of dosage and treatment course. According to the survey, 17.6% (90/511) of the clinicians believed that comprehensive assessment of the patient′s clinical condition was not necessary for the diagnosis and treatment of FGID. Conclusion:Gastroenterologists are familiar with the basic concepts of SIBO, but their understanding of the diagnostic criteria application and the latest research progress is limited.
6.A survey on the current knowledge of small intestinal bacterial overgrowth among Chinese gastroenterology clinicians
Mengyu ZHANG ; Fangfei CHEN ; Niandi TAN ; Yinglian XIAO
Chinese Journal of Digestion 2025;45(8):541-547
Objective:To investigate the current level of awareness among Chinese gastroenterologists regarding small intestinal bacterial overgrowth (SIBO).Methods:From March 7th to April 14th, 2024, an online survey questionnaire was sent to qualified clinical physicians specializing in gastroenterology in various levels of general hospitals across the country through the official channels of national academic organizations such as the Gastroenterology Branch of the Chinese Medical Association, the Gastrointestinal Motility Group of the Gastroenterology Branch of the Chinese Medical Association, and the Functional Gastrointestinal Disorders Collaborative Group of the Gastroenterology Branch of the Chinese Medical Association, as well as through the national medical continuing education project cooperation platform. The questionnaire content includes basic information, awareness of consensus guidelines on functional gastrointestinal disorders (FGID) and SIBO, understanding of SIBO and its diagnosis and treatment strategies, et al. The influencing factors of physicians′ cognitive level regarding SIBO were analyzed based on the questionnaire results. Statistical methods employed descriptive statistical method and partial correlation analysis.Results:A total of 511 valid questionnaires were collected, among them, 78.1% (399/511) of the respondents practiced in tertiary hospitals, and 90.2% (461/511) of the respondents were aware of the definition of SIBO. However, only 9.0% (46/511) could accurately identify all the key points of the relevant consensus guidelines. Educational background (undergraduate and master′s degree vs. doctor degree, OR=0.265, 0.528, 95% confidence interval(95% CI): 0.155 to 0.454, 0.322 to 0.865), professional title (junior title vs. senior title, OR=0.577, 95% CI: 0.344 to 0.968), and the number of SIBO cases handled per year (less than 50 cases vs. more than 200 cases, OR=0.144, 95% CI: 0.043 to 0.479) were independent influencing factors that affect the cognitive level of specialist physicians regarding SIBO and the guidelines (all P<0.05). The results of hydrogen and methane breath test (HMBT) was the main reference indicator for diagnosing SIBO in the respondents (79.8%, 408/511), but only 8.4%(43/511) of the specialists were familiar with the principle of HMBT, and 65.9% (337/511) were not clear about the differences in diagnostic thresholds among different consensus or guidelines. Rifaximin was the most commonly used therapy (87.5%, 447/511), but there was significant heterogeneity in the selection of dosage and treatment course. According to the survey, 17.6% (90/511) of the clinicians believed that comprehensive assessment of the patient′s clinical condition was not necessary for the diagnosis and treatment of FGID. Conclusion:Gastroenterologists are familiar with the basic concepts of SIBO, but their understanding of the diagnostic criteria application and the latest research progress is limited.
7.The Disease Spectrum and Natural History of Patients With Abdominal Bloating or Distension:A Longitudinal Study
Fangfei CHEN ; Niandi TAN ; Songfeng CHEN ; Qianjun ZHUANG ; Mengyu ZHANG ; Yinglian XIAO
Journal of Neurogastroenterology and Motility 2024;30(1):64-72
Background/Aims:
Abdominal bloating or distension (AB/D) is a common complaint in the outpatient of gastroenterology department. Since the potential contributors are numerous and complex, a longitudinal study on the disease spectrum and natural history of patients was performed to better understand the key factors of AB/D.
Methods:
Consecutive patients with the chief complaint of AB/D referred to the outpatient clinic were screened. Functional gastrointestinal disorders (FGIDs) were diagnosed according to Rome IV criteria. A 3-year follow-up was performed to seek for the changes in symptoms as well as disease spectrum.
Results:
A total of 261 participants were enrolled and 139 completed the follow-up. Most patients suffered from moderate to severe symptoms more than 1 day per week. Common causes of AB/D were FGIDs (51.7%) and organic diseases (17.2%). The latter group was older with lower body mass index (BMI). Functional dyspepsia was the most common type of FGIDs in AB/D. The symptoms of 18.0% of participants failed to improve at the end of the 3-year follow-up, and those diagnosed with FGIDs were most likely to continue to suffer. Abdominal pain was a positive predictive factor for good prognosis in the FGIDs group. Besides, only 22.7% of participants had a consistent diagnosis of FGIDs during follow-up.
Conclusions
FGIDs are the most common diagnosis in patients with AB/D. Symptoms were especially hard to be improved. Classification diagnoses of FGIDs in AB/D patients fluctuated significantly over time.
8.The effects of mast cells and 5-hydroxytryptamine on the efficacy of Shugan Jieyu capsule in the treatment of functional dyspepsia
Zhanye ZHANG ; Qianjun ZHUANG ; Xingyu JIA ; Niandi TAN ; Fangfei CHEN ; Mengyu ZHANG ; Songfeng CHEN ; Junnan HU ; Yinglian XIAO
Chinese Journal of Digestion 2024;44(10):679-685
Objective:To investigate the possible targets of Shugan Jieyu capsules (SGJY) in the treatment of functional dyspepsia (FD).Methods:From January 1, 2022 to September 30, 2023, a total of 36 FD patients who visited the Department of Gastroenterology and Hepatology, the First Affiliated Hospital of Sun Yat-sen University were prospectively enrolled, and 10 healthy controls were included during the same period. The symptoms and quality of life of FD patients and healthy controls were evaluated with FD symptom scale and short form-Nepean dyspepsia index (SF-NDI), respectively, the anxiety and depression status of FD patients and healthy controls were assessed with the hospital anxiety and depression scale (HADS). The mucosal tissues of gastric fundus and descending duodenum were collected to count the numbers of eosinophils, mast cells, 5-hydroxytryptamine-positive (5-HT + ) cells and detect the expression of zonula occluden-1(ZO-1), occludin, and Claudin 2. FD patients received SGJY (0.72 g, twice daily) for 6 weeks. After treatment, a decrease in FD symptom score of >50% compared with baseline was considered as SGJY response, while a decrease of <50% was considered as SGJY non-response. Receiver operating characteristic cuve (ROC) analysis was performed to analyze and evaluate the predictive value of indicators for the response of SGJY, and Spearman rank correlation was used for correlation analysis. One-way analysis of variance, Kruskal-Wallis H test, and chi-square test were used for statistical analysis. Results:A total of 9 FD patients without anxiety or depression, and 27 FD patients with anxiety or depression were included. Among the 36 FD patients, 18 patients responded to SGJY, with a response rate 50.0%. Eleven FD patients with anxiety or depression responded to SGJY, 7 FD patients without anxiety or depression responded to SGJY. HADS scores and SF-NDI scores of FD patients with anxiety or depression were all higher than those of FD patients without anxiety or depression and healthy controls (8.7±0.7 vs. 4.0±0.6 and 3.5±0.8; 10.4±0.6 vs. 4.0±0.7 and 5.0±0.8; 29.0(22.5, 36.0) vs. 21.0 (14.0, 24.5) and 10.0 (10.0, 13.3)); and the differences were statistically significant ( F=14.50, 27.07; H=25.19; all P<0.001). The 5-HT + cell count in the descending duodenum and mast cell count in the gastric fundus and degranulation score of SGJY responders were all higher than those of SGJY non-responders and healthy controls ((65.8±4.1)/mm 2vs. (54.9±3.6) and (48.3±3.7)/mm 2, (14.0±1.2)/high power field vs. (10.5±0.7) and (9.0±1.1)/high power field, 7.5±0.5 vs. 5.7±0.4 and 3.4±0.4); and the differences were statistically significant ( F=4.38, 3.72, 12.56; all P<0.05). There were no statistically significant differences in the 5-HT + cell count in the descending duoclenum and mast cell count in the gastric fundus between non-responders and healthy controls (all P>0.05). The results of Spearman rank correlation showed that mast cell count in the gastric fundus degranulation score positively correlated with total symptom score ( r=0.636, P<0.001). In FD patients with anxiety or depression, the 5-HT + cell count in the descending duodenum and mast cell count in the gastric fundus and degranulation score of SGJY responders were higher than those of SGJY non-responders and healthy controls ((68.9±6.3)/mm 2vs. (48.0±3.4) and (56.0±4.1)/mm 2, (14.8±1.7)/high power field vs. (9.0±1.1) and (11.0±0.8)/high power field, 7.3±0.6 vs. 5.6±0.5 and 3.4±0.4); and the differences were statistically significant ( F=4.10, 5.56, 12.38; all P<0.05). The result of ROC analysis revealed that 5-HT + cell count in the descending duoclenum could predict the response to SGJY. When the cut-off value of 5-HT + cell count in the descending duoclenum was 55.12 /mm 2, the sensitivity was 82.4% and the specificity was 61.1% (area under the curve=0.700, P=0.046). Conclusion:SGJY may alleviate FD symptoms by inhibiting mast cell in the gastric fundus and regulating 5-HT + cell in the descending duoclenum.
9.The effects of mast cells and 5-hydroxytryptamine on the efficacy of Shugan Jieyu capsule in the treatment of functional dyspepsia
Zhanye ZHANG ; Qianjun ZHUANG ; Xingyu JIA ; Niandi TAN ; Fangfei CHEN ; Mengyu ZHANG ; Songfeng CHEN ; Junnan HU ; Yinglian XIAO
Chinese Journal of Digestion 2024;44(10):679-685
Objective:To investigate the possible targets of Shugan Jieyu capsules (SGJY) in the treatment of functional dyspepsia (FD).Methods:From January 1, 2022 to September 30, 2023, a total of 36 FD patients who visited the Department of Gastroenterology and Hepatology, the First Affiliated Hospital of Sun Yat-sen University were prospectively enrolled, and 10 healthy controls were included during the same period. The symptoms and quality of life of FD patients and healthy controls were evaluated with FD symptom scale and short form-Nepean dyspepsia index (SF-NDI), respectively, the anxiety and depression status of FD patients and healthy controls were assessed with the hospital anxiety and depression scale (HADS). The mucosal tissues of gastric fundus and descending duodenum were collected to count the numbers of eosinophils, mast cells, 5-hydroxytryptamine-positive (5-HT + ) cells and detect the expression of zonula occluden-1(ZO-1), occludin, and Claudin 2. FD patients received SGJY (0.72 g, twice daily) for 6 weeks. After treatment, a decrease in FD symptom score of >50% compared with baseline was considered as SGJY response, while a decrease of <50% was considered as SGJY non-response. Receiver operating characteristic cuve (ROC) analysis was performed to analyze and evaluate the predictive value of indicators for the response of SGJY, and Spearman rank correlation was used for correlation analysis. One-way analysis of variance, Kruskal-Wallis H test, and chi-square test were used for statistical analysis. Results:A total of 9 FD patients without anxiety or depression, and 27 FD patients with anxiety or depression were included. Among the 36 FD patients, 18 patients responded to SGJY, with a response rate 50.0%. Eleven FD patients with anxiety or depression responded to SGJY, 7 FD patients without anxiety or depression responded to SGJY. HADS scores and SF-NDI scores of FD patients with anxiety or depression were all higher than those of FD patients without anxiety or depression and healthy controls (8.7±0.7 vs. 4.0±0.6 and 3.5±0.8; 10.4±0.6 vs. 4.0±0.7 and 5.0±0.8; 29.0(22.5, 36.0) vs. 21.0 (14.0, 24.5) and 10.0 (10.0, 13.3)); and the differences were statistically significant ( F=14.50, 27.07; H=25.19; all P<0.001). The 5-HT + cell count in the descending duodenum and mast cell count in the gastric fundus and degranulation score of SGJY responders were all higher than those of SGJY non-responders and healthy controls ((65.8±4.1)/mm 2vs. (54.9±3.6) and (48.3±3.7)/mm 2, (14.0±1.2)/high power field vs. (10.5±0.7) and (9.0±1.1)/high power field, 7.5±0.5 vs. 5.7±0.4 and 3.4±0.4); and the differences were statistically significant ( F=4.38, 3.72, 12.56; all P<0.05). There were no statistically significant differences in the 5-HT + cell count in the descending duoclenum and mast cell count in the gastric fundus between non-responders and healthy controls (all P>0.05). The results of Spearman rank correlation showed that mast cell count in the gastric fundus degranulation score positively correlated with total symptom score ( r=0.636, P<0.001). In FD patients with anxiety or depression, the 5-HT + cell count in the descending duodenum and mast cell count in the gastric fundus and degranulation score of SGJY responders were higher than those of SGJY non-responders and healthy controls ((68.9±6.3)/mm 2vs. (48.0±3.4) and (56.0±4.1)/mm 2, (14.8±1.7)/high power field vs. (9.0±1.1) and (11.0±0.8)/high power field, 7.3±0.6 vs. 5.6±0.5 and 3.4±0.4); and the differences were statistically significant ( F=4.10, 5.56, 12.38; all P<0.05). The result of ROC analysis revealed that 5-HT + cell count in the descending duoclenum could predict the response to SGJY. When the cut-off value of 5-HT + cell count in the descending duoclenum was 55.12 /mm 2, the sensitivity was 82.4% and the specificity was 61.1% (area under the curve=0.700, P=0.046). Conclusion:SGJY may alleviate FD symptoms by inhibiting mast cell in the gastric fundus and regulating 5-HT + cell in the descending duoclenum.
10.Achalasia: The Current Clinical Dilemma and Possible Pathogenesis
Xingyu JIA ; Songfeng CHEN ; Qianjun ZHUANG ; Niandi TAN ; Mengyu ZHANG ; Yi CUI ; Jinhui WANG ; Xiangbin XING ; Yinglian XIAO
Journal of Neurogastroenterology and Motility 2023;29(2):145-155
Achalasia is a primary esophageal motility disorder manifested by dysphagia and chest pain that impair patients’ quality of life, and it also leads to chronic esophageal inflammation by food retention and increases the risk of esophageal cancer. Although achalasia has long been reported, the epidemiology, diagnosis and treatment of achalasia are not fully understood. The current clinical dilemma of achalasia is mainly due to its unclear pathogenesis. In this paper, epidemiology, diagnosis treatment, as well as possible pathogenesis of achalasia will be reviewed and summarized. The proposed hypothesis on the pathogenesis of achalasia is that genetically susceptible populations potentially have a higher risk of infection with viruses, triggering autoimmune and inflammation responses to inhibitory neurons in lower esophageal sphincter.

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