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.

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.