OBJECTIVE: To explore the genetic etiology of 46 Chinese pedigrees affected with Hereditary multiple exostoses (HME) and provide genetic counseling and reproductive intervention. METHODS: Whole-exome sequencing and Sanger sequencing were carried out on 87 patients from the 46 pedigrees to analyze the variants of EXT1 and EXT2 genes. Pathogenicity of the variants was assessed based on the guidelines from the American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG/AMP). Prenatal diagnosis and preimplantation genetic testing (PGT) were provided for couples with identified pathogenic mutations. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: LL-SC-SG-2014-010). RESULTS: In total 17 and 22 pathogenic variants were respectively identified in the EXT1 and EXT2 genes, among which 5 EXT1 and 12 EXT2 variants were unreported previously. Three patients with no family history were found to harbor de novo variants of the EXT1 gene. Twenty nine couples had opted for PGT or underwent prenatal diagnosis following natural conception, and 17 healthy babies were born. CONCLUSION This study has clarified the genetic etiology of 45 HME pedigrees and identified 17 novel variants, which has enriched the mutational spectrum of the EXT1 and EXT2 genes. Reproductive intervention through PGT and prenatal diagnosis have prevented the recurrence of HME in these families.
Humans ; Female ; Male ; Pedigree ; Exostoses, Multiple Hereditary/diagnosis* ; N-Acetylglucosaminyltransferases/genetics* ; Adult ; Exostosin 1 ; Asian People/genetics* ; Genetic Testing ; Exostosin 2 ; Mutation ; China ; Prenatal Diagnosis ; Pregnancy ; Genetic Counseling ; Preimplantation Diagnosis ; Exome Sequencing ; East Asian People

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.

Objective:This study aims to conduct a systematic review and network meta-analysis comparing the safety and efficacy of endoscopic versus surgical treatments for gastroesophageal reflux disease (GERD).Methods:Randomized controlled trials were identified through systematic searches of MEDLINE, Embase, Web of Science, and CNKI. Both direct effect models and Bayesian random-effects network meta-analysis were used to compare treatments directly and indirectly. The following types of studies were included : (1) RCTs involving endoscopic or surgical treatment for adult GERD patients aged ≥18 years with no previous history of gastroesophageal surgery; (2) studies comparing two or more treatment methods, including different endoscopic or surgical procedures, proton pump inhibitor (PPI) therapy, and/or sham surgery; and (3) articles published in Chinese or English. Review articles and conference abstracts were excluded.Results:A total of 47 randomized controlled trials were enrolled, and 43 studies were network meta-analyzed. Both endoscopic and surgical treatments significantly reduced postoperative PPI use compared to PPI therapy ( P <0.05). Among all treatment modalities, laparoscopic Nissen fundoplication (LNF, SUCRA=0.84) demonstrated the highest efficacy, followed by laparoscopic Toupet fundoplication (LTF, SUCRA=0.71) and anterior partial fundoplication (APF, SUCRA=0.70). Transoral incisionless fundoplication (TIF) demonstrated the best outcomes in relieving heartburn (SUCRA=0.87) and bloating (SUCRA=0.86) symptoms. The overall safety of surgical treatment was comparable to that of PPI therapy. However, LNF was associated with a higher incidence of postoperative dysphagia and gas-related symptoms, whereas TIF had a lower risk of postoperative complications. Conclusions:Both endoscopic and surgical treatments are effective for GERD. LNF provides the highest rate of medication discontinuation but carries a higher risk of postoperative complications. TIF offers better relief of heartburn and bloating with fewer complications.

Objective To study the types of articulation errors in children with speech sound disorders(SSD)and compare the differences in articulation between two groups according to their ages of language development(≥4 years and＜4 years).Methods A comprehensive assessment was conducted on 260 children with SSD who visited the outpatient department between May 2022 and May 2023.The S-S method for delayed language development e-valuation and the Gesell developmental schedules were used.Based on their assessed language developmental age,130 children from each age group(≥4 years and＜4 years)were selected.All participants underwent speech articu-lation assessment using the Word List developed by Huang Zhaoming and Han Zhijuan.The types of consonant and vowel mispronunciations were compared between the two groups,and statistical analysis were performed using SPSS 26.0 software to determine differences in speech articulation.Results Apart from distortions,the most common type of consonant mispronunciation in both age groups was frontalization,while the most frequent type of vowel mispronunciation was final sound omission.The occurrence frequency and composition ratio of consonant and vowel mispronunciations were similar in both age groups,and there was no significant difference in speech articulation be-tween the two groups of children.Conclusion Early intervention is crucial for children with SSDs at different lan-guage developmental stages(≥4 years and＜4 years)to prevent the solidification of incorrect articulation patterns.

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.

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.

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.

Objective:This study aims to conduct a systematic review and network meta-analysis comparing the safety and efficacy of endoscopic versus surgical treatments for gastroesophageal reflux disease (GERD).Methods:Randomized controlled trials were identified through systematic searches of MEDLINE, Embase, Web of Science, and CNKI. Both direct effect models and Bayesian random-effects network meta-analysis were used to compare treatments directly and indirectly. The following types of studies were included : (1) RCTs involving endoscopic or surgical treatment for adult GERD patients aged ≥18 years with no previous history of gastroesophageal surgery; (2) studies comparing two or more treatment methods, including different endoscopic or surgical procedures, proton pump inhibitor (PPI) therapy, and/or sham surgery; and (3) articles published in Chinese or English. Review articles and conference abstracts were excluded.Results:A total of 47 randomized controlled trials were enrolled, and 43 studies were network meta-analyzed. Both endoscopic and surgical treatments significantly reduced postoperative PPI use compared to PPI therapy ( P <0.05). Among all treatment modalities, laparoscopic Nissen fundoplication (LNF, SUCRA=0.84) demonstrated the highest efficacy, followed by laparoscopic Toupet fundoplication (LTF, SUCRA=0.71) and anterior partial fundoplication (APF, SUCRA=0.70). Transoral incisionless fundoplication (TIF) demonstrated the best outcomes in relieving heartburn (SUCRA=0.87) and bloating (SUCRA=0.86) symptoms. The overall safety of surgical treatment was comparable to that of PPI therapy. However, LNF was associated with a higher incidence of postoperative dysphagia and gas-related symptoms, whereas TIF had a lower risk of postoperative complications. Conclusions:Both endoscopic and surgical treatments are effective for GERD. LNF provides the highest rate of medication discontinuation but carries a higher risk of postoperative complications. TIF offers better relief of heartburn and bloating with fewer complications.

Objective To study the types of articulation errors in children with speech sound disorders(SSD)and compare the differences in articulation between two groups according to their ages of language development(≥4 years and＜4 years).Methods A comprehensive assessment was conducted on 260 children with SSD who visited the outpatient department between May 2022 and May 2023.The S-S method for delayed language development e-valuation and the Gesell developmental schedules were used.Based on their assessed language developmental age,130 children from each age group(≥4 years and＜4 years)were selected.All participants underwent speech articu-lation assessment using the Word List developed by Huang Zhaoming and Han Zhijuan.The types of consonant and vowel mispronunciations were compared between the two groups,and statistical analysis were performed using SPSS 26.0 software to determine differences in speech articulation.Results Apart from distortions,the most common type of consonant mispronunciation in both age groups was frontalization,while the most frequent type of vowel mispronunciation was final sound omission.The occurrence frequency and composition ratio of consonant and vowel mispronunciations were similar in both age groups,and there was no significant difference in speech articulation be-tween the two groups of children.Conclusion Early intervention is crucial for children with SSDs at different lan-guage developmental stages(≥4 years and＜4 years)to prevent the solidification of incorrect articulation patterns.

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.