Intestinal mucositis is a common complication induced by chemotherapy in malignant tumors， which severely compromises the efficacy of chemotherapy and reduces patients’ quality of life. This article systematically reviews the pathological mechanisms underlying chemotherapy-induced intestinal mucositis， encompassing oxidative damage， inflammatory injury， apoptotic damage， disruption of the intestinal barrier， and intestinal dysbiosis. Additionally， it provides a comprehensive summary of current therapeutic strategies for intestinal mucositis， including chemical agents and composite materials， natural products， compound prescription of traditional Chinese medicine， growth factors， blood products， and fecal microbiota transplantation. Future efforts should strengthen multidisciplinary cross-innovation， integrating animal models and large-scale clinical trials to develop highly effective and low-toxicity therapeutic drugs that balance chemotherapy toxicity and antitumor efficacy.

Objective:To evaluate the efficacy and safety of mosapride citrate dispersible tablet (MP) combined with Shugan Jieyu capsule (SGJY) in the treatment of functional dyspepsia (FD).Methods:From April 2018 to January 2019, FD patients from 10 hospitals including Renji Hospital, Shanghai Jiaotong University School of Medicine, Luohe Hospital of Traditional Chinese Medicine, the Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Handan Hospital of Traditional Chinese Medicine and Nanshi Hospital of Nanyang were selected for a randomized, double-blind, placebo-controlled trial. The patient health questionnaire-9 (PHQ-9) and generalized anxiety disorder-7 (GAD-7) were used to assess depression and anxiety in FD patients, respectively. According to the random number table method, 200 FD patients who met the inclusion criteria were randomly divided into SGJY+ MP group and placebo+ MP group, with 100 patients in each group, and all the patients were given oral MP. The patients of the SGJY+ MP group and the placebo+ MP group were given oral SGJY or placebo on the basis of MP, respectively. The patients of both groups were treated continuously for 6 weeks. Total FD symptom scores, PHQ-9 and GAD-7 scores, as well as efficiency and safety were evaluated after treatment. Independent samples t-test and chi-square test were used for statistical analysis. Results:A total of 193 patients were included into the full analysis set with 94 cases in the SGJY+ MP group and 99 cases in the placebo+ MP group. A total of 183 patients completed the 6-week trial, including 89 cases in the SGJY+ MP group and 94 cases in the placebo+ MP group. A total of 198 patients were included in the safety analysis set, including 99 cases in the SGJY+ MP group and 99 cases in the placebo+ MP group.After treatment, the total FD symptom scores of the SGJY+ MP group and the placebo+ MP group were both lower than those of baseline before treatment (3.71±3.06 vs. 11.79±5.18 and 4.17±3.69 vs. 11.19±5.05), and the differences were both statistically significant ( t=-24.87 and -23.27, both P<0.001). The efficacy of the SGJY+ MP group was higher than that of the placebo+ MP group (86.5%, 77/89 vs. 74.5%, 70/94), and the difference was statistically significant ( χ2=4.69, P=0.030). The efficacy of patients with moderate-to-severe anxiety and depression in the SGJY+ MP group was both higher than that of patients in the placebo+ MP group (10/10 vs. 3/7, 85.0%, 17/20 vs. 8/14), and the differences were statistically significant ( χ2=5.66 and 5.33, P=0.017 and 0.010). The efficacy of patients with postprandial distress syndrome (PDS) subtype in the SGJY+ MP group was higher than that of patients in the placebo+ MP group (93.0%, 53/57 vs. 76.5%, 39/51), and the difference was statistically significant (χ 2=5.82, P=0.016). The PHQ-9 scores of patients with depression in both SGJY+ MP and placebo+ MP groups were lower than those at baseline before treatment (3.63±2.76 vs. 7.87±2.24 and 3.35±2.51 vs. 7.63±2.25), and the differences were statistically significant ( t=-14.88 and -15.87, both P<0.001). There was no significant difference in proportion of depressed patients with a ≥50% reduction in PHQ-9 scores from baseline value between the SGJY+ MP group and the placebo+ MP group (60.2%, 50/83 vs. 62.8%, 54/86; χ2=0.05, P=0.825). The GAD-7 scores of anxious patients both the SGJY+ MP group and the placebo+ MP group were lower than the baseline value before treatment (3.27±2.57 vs. 7.09±2.08 and 3.86±2.49 vs. 6.84±1.66), and the differences were statistically significant ( t=-13.30 and -11.47, both P<0.001). The proportion of anxious patients with a ≥50% reduction in GAD-7 scores from baseline in the SGJY+ MP group was higher than that of the placebo+ MP group (54.4%, 43/79 vs. 36.5%, 27/74), and the difference was statistically significant ( χ2=4.53, P=0.033). There were no serious adverse events in both the SGJY+ MP group and the placebo+ MP group during the treatment. There were no significant differences in the incidence of adverse events and adverse reactions during the treatment between the SGJY+ MP group and the placebo+ MP group (7.1%, 7/99 vs. 5.1%, 5/99, and 3.0%, 3/99 vs. 3.0%, 3/99, respectively; both P>0.05). Conclusion:SGTY can safely and effectively improve the efficacy of the prokinetic drugs in the treatment of FD symptoms, especially in FD patients with PDS subtype or with moderate-to-severe anxiety and with depression.

Objective:To evaluate the efficacy and safety of mosapride citrate dispersible tablet (MP) combined with Shugan Jieyu capsule (SGJY) in the treatment of functional dyspepsia (FD).Methods:From April 2018 to January 2019, FD patients from 10 hospitals including Renji Hospital, Shanghai Jiaotong University School of Medicine, Luohe Hospital of Traditional Chinese Medicine, the Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Handan Hospital of Traditional Chinese Medicine and Nanshi Hospital of Nanyang were selected for a randomized, double-blind, placebo-controlled trial. The patient health questionnaire-9 (PHQ-9) and generalized anxiety disorder-7 (GAD-7) were used to assess depression and anxiety in FD patients, respectively. According to the random number table method, 200 FD patients who met the inclusion criteria were randomly divided into SGJY+ MP group and placebo+ MP group, with 100 patients in each group, and all the patients were given oral MP. The patients of the SGJY+ MP group and the placebo+ MP group were given oral SGJY or placebo on the basis of MP, respectively. The patients of both groups were treated continuously for 6 weeks. Total FD symptom scores, PHQ-9 and GAD-7 scores, as well as efficiency and safety were evaluated after treatment. Independent samples t-test and chi-square test were used for statistical analysis. Results:A total of 193 patients were included into the full analysis set with 94 cases in the SGJY+ MP group and 99 cases in the placebo+ MP group. A total of 183 patients completed the 6-week trial, including 89 cases in the SGJY+ MP group and 94 cases in the placebo+ MP group. A total of 198 patients were included in the safety analysis set, including 99 cases in the SGJY+ MP group and 99 cases in the placebo+ MP group.After treatment, the total FD symptom scores of the SGJY+ MP group and the placebo+ MP group were both lower than those of baseline before treatment (3.71±3.06 vs. 11.79±5.18 and 4.17±3.69 vs. 11.19±5.05), and the differences were both statistically significant ( t=-24.87 and -23.27, both P<0.001). The efficacy of the SGJY+ MP group was higher than that of the placebo+ MP group (86.5%, 77/89 vs. 74.5%, 70/94), and the difference was statistically significant ( χ2=4.69, P=0.030). The efficacy of patients with moderate-to-severe anxiety and depression in the SGJY+ MP group was both higher than that of patients in the placebo+ MP group (10/10 vs. 3/7, 85.0%, 17/20 vs. 8/14), and the differences were statistically significant ( χ2=5.66 and 5.33, P=0.017 and 0.010). The efficacy of patients with postprandial distress syndrome (PDS) subtype in the SGJY+ MP group was higher than that of patients in the placebo+ MP group (93.0%, 53/57 vs. 76.5%, 39/51), and the difference was statistically significant (χ 2=5.82, P=0.016). The PHQ-9 scores of patients with depression in both SGJY+ MP and placebo+ MP groups were lower than those at baseline before treatment (3.63±2.76 vs. 7.87±2.24 and 3.35±2.51 vs. 7.63±2.25), and the differences were statistically significant ( t=-14.88 and -15.87, both P<0.001). There was no significant difference in proportion of depressed patients with a ≥50% reduction in PHQ-9 scores from baseline value between the SGJY+ MP group and the placebo+ MP group (60.2%, 50/83 vs. 62.8%, 54/86; χ2=0.05, P=0.825). The GAD-7 scores of anxious patients both the SGJY+ MP group and the placebo+ MP group were lower than the baseline value before treatment (3.27±2.57 vs. 7.09±2.08 and 3.86±2.49 vs. 6.84±1.66), and the differences were statistically significant ( t=-13.30 and -11.47, both P<0.001). The proportion of anxious patients with a ≥50% reduction in GAD-7 scores from baseline in the SGJY+ MP group was higher than that of the placebo+ MP group (54.4%, 43/79 vs. 36.5%, 27/74), and the difference was statistically significant ( χ2=4.53, P=0.033). There were no serious adverse events in both the SGJY+ MP group and the placebo+ MP group during the treatment. There were no significant differences in the incidence of adverse events and adverse reactions during the treatment between the SGJY+ MP group and the placebo+ MP group (7.1%, 7/99 vs. 5.1%, 5/99, and 3.0%, 3/99 vs. 3.0%, 3/99, respectively; both P>0.05). Conclusion:SGTY can safely and effectively improve the efficacy of the prokinetic drugs in the treatment of FD symptoms, especially in FD patients with PDS subtype or with moderate-to-severe anxiety and with depression.

【Objective】 To develop methods to display the IgG autoantibody repertoire of intravenous immunoglobulin (IVIG) products, analyze the different types of antibodies and study the diversity of IgG autoantibody in 4 IVIG preparations from different Chinese manufacturers. 【Methods】 Two-dimensional gel electrophoresis and immunoblotting with human umbilical vein endothelial cell (HUVEC) proteins were used to demonstrate the IgG autoantibody repertoire and the human protein microarray with bioinformatics analysis was employed to profile the immune reactive autoantigens of the 4 IVIG preparations. 【Results】 The methods to showcase the autoantibody repertoire and study the antibody diversity of IVIG were successfully established. High-quality repertoires of IVIG autoantibodies and biological information about self-proteins that can be recognized were obtained. There was a significant difference in the recognition of the quantity and variety of the self-antigens by different IVIG products. The number of antibodies against HUVEC proteins in four products ranged from 241-386. The number of proteins recognized on the human protein chip ranged from 292-435, with 172 human self-proteins recognized by all four products. 【Conclusion】 Demonstration of antibody repertoire and protein chip technology can be used to analyze IVIG products′ IgG autoantibody repertoire. All four preparations tested in this study exhibited a broad spectrum of antibodies against HUVEC proteins and human proteome microarray, each product had its unique antibody repertoire characteristics.

Endoscopic anterior fundoplication with the MUSE is an endoscopic therapy that combines ultrasound and endoscopic anti-reflux technology for moderate to severe gastroesophageal reflux disease. Training and learning procedures are required to obtain qualifications for this endoscopic therapy before clinical operations. At present, there is limited high-quality evidence-based medical evidence on MUSE treatment, and lack of expert consensus or guidance for training and the standard of MUSE therapy procedure. This consensus is based on the published literature, and formulated by experts with MUSE clinical experience in China, to provide guidance for the training and clinical standard operation of this technique.

Overlapping symptoms are common in functional gastrointestinal disorders(FGIDs).The treatment of FGIDs is based on promoting gastrointestinal motility and improving visceral hypersensitivity,however,the efficacy is limited.Emerging data suggest the presence of low-grade duodenal inflammation with predominant eosinophilic infiltration in functional dyspepsia(FD)patients,accompanied by impaired epithelial barrier,increased permeability and increased pyroptosis,etc.,especially in FD patients overlapping gastroesophageal reflux disease(GERD)and/or irritable bowel syndrome(IBS).The etiologies of FGIDs include infection,stress,food antigens,irregular diet etc.,and can increase mucosal permeability,involve in the gut-brain interaction via activating duodenal mucosal eosinophil-mast cell axis,thus causing the symptoms of FGIDs as well as the overlapping symptoms.This article reviewed advances in research on duodenal inflammation and overlapping symptoms of FGIDs.

Endoscopic anterior fundoplication with the MUSE is an endoscopic therapy that combines ultrasound and endoscopic anti-reflux technology for moderate to severe gastroesophageal reflux disease.Training and learning procedures are required to obtain qualifications for this endoscopic therapy before clinical operations.At present,there is limited high-quality evidence-based medical evidence on MUSE treatment,and lack of expert consensus or guidance for training and the standard of MUSE therapy procedure.This consensus is based on the published literature,and formulated by experts with MUSE clinical experience in China,to provide guidance for the training and clinical standard operation of this technique.

Background: Epidemiological evidence revealed that stress is the causative factor of dyspeptic symptoms. It has been documented that duodenal inflammation is one of the key mechanisms of dyspepsia, and macrophage is crucial for inflammation. Aims: To determine whether patients with functional dyspepsia (FD) comorbid psychological stress have duodenal inflammation. Furthermore, to identify whether macrophage is involved in the mechanisms of stress-related duodenal inflammation by using water avoidance stress (WAS)animal model. Methods: Duodenal inflammation was observed and compared between FD patients with psychological factors and asymptomatic healthy controls. WAS mouse model with 1 h stress daily for 10 days was used to evaluate the duodenal inflammation at different time points to describe its dynamic changes. The role of macrophage in the development of duodenal inflammation was determined in an interventional study, in which the resident macrophages were depleted by clodronate liposomes. In both clinical and animal studies, the severity of duodenal inflammation was assessed by HE staining and immunocyte counts, the macrophage infiltration was detected by immunohistochemistry, and the expression of inflammatory cytokines was detected by real-time PCR. Results: FD patients with psychological factors developed severe duodenal inflammation in comparison with the healthy controls (immunocytes/HPF: 138.91±7.13 vs. 81.44±23.60, P<0.000 1). At the same time, the expressions of proinflammatory cytokines (IL-1β, TNF-α, and IL-17A) were increased, while the expressions of anti-inflammatory cytokines (IL-10 and TGF-β) were decreased (all P<0.05). In WAS mouse model, a dynamic change in duodenal inflammation which peaked on day 5 was observed, and the changes of macrophage infiltrating in the duodenal tissue were consistent with the duodenal inflammation. Clodronate liposomes pretreatment could effectively deplete macrophages, protected the WAS mouse model against duodenal inflammation (immunocytes/HPF: 75.10±4.08 vs. 202.43±5.18, P<0.001), with a marked reduction of the expressions of proinflammatory cytokines (IL-1β, TNF-α, and IL-8), and a marked elevation of the expression of anti-inflammatory cytokine IL-10 (all P<0.05). Conclusions: Psychological stress may lead to dyspeptic symptoms via macrophage-mediated duodenal inflammation.

BACKGROUND/AIMS: Abdominal pain can be evoked or exacerbated after gastrointestinal cold stimulation in some patients with diarrhea-predominant irritable bowel syndrome (IBS-D), indicating a low temperature-induced sensitization of visceral perception. We investigated the role of vagal transient receptor potential ankyrin 1 (TRPA1, a cold-sensing ion channel) in cold-aggravated visceral mechanonociception in a stress-induced IBS animal model. METHODS: TRPA1 expression was examined in antral biopsies of healthy controls and IBS-D patients. Abdominal symptoms were assessed before and after warm or cold water intake. The visceromotor response (VMR) to colorectal distention (CRD) following intra-antral infusion of cold saline was measured in animals undergoing sham or chronic water avoidance stress. TRPA1 expression, extracellular signal-regulated protein kinase 1/2 (ERK1/2) phosphorylation, and neuronal calcium influx in vagal afferents were assessed. RESULTS: Compared to healthy controls, IBS-D patients displayed elevated antral TRPA1 expression, which was associated with symptom scores after cold (4°C) water intake. Intra-antral infusion of cold saline increased VMR to CRD in naive rats, an effect dependent on vagal afferents. In stressed rats, this effect was greatly enhanced. Functional blockade and gene deletion of TRPA1 abolished the cold effect on visceral nociception. TRPA1 expression in vagal (but not spinal) afferents increased after stress. Moreover, the cold-induced, TRPA1-dependent ERK1/2 activation and calcium influx in nodose neurons were more robust in stressed rats. CONCLUSIONS: Stress-exaggerated visceral mechanonociception after antral cold exposure may involve up-regulation of TRPA1 expression and function on vagal afferents. Our findings reveal a novel mechanism for abnormal gastrointestinal cold sensing in IBS.
Abdominal Pain ; Animals ; Ankyrins ; Biopsy ; Calcium ; Cold Temperature ; Drinking ; Gene Deletion ; Humans ; Irritable Bowel Syndrome ; Models, Animal ; Neurons ; Nociception ; Phosphorylation ; Protein Kinases ; Rats ; Stress, Psychological ; Up-Regulation ; Vagus Nerve ; Visceral Pain ; Water

OBJECTIVE： To establish HPLC fingerprints of Ligusticum chuanxiong decoction pieces， and to conduct cluster analysis and PLS-DA analysis. METHODS： HPLC method was adopted. The determination was performed on Waters Symmetry C18 column with mobile phase consisted of acetonitrile-0.5％ acetic acid solution （gradient elution） at the flow rate of 1 mL/min. The detection wavelength was set at 254 nm， and the column temperature was 30 ℃. The sample size was 10 μL. Using ligustilide as control， HPLC chromatograms of 21 batches of samples （S1-S20） were determined. The similarity evaluation was conducted by using Similarity Evaluation System for Chromatographic Fingerprint of TCM （2012 edition） to determine common peak. Cluster analysis was conducted by using SPSS 19.0 software and PLS-DA was used to distinguish the samples. RESULTS： There were 25 common peaks in HPLC chromatograms for 21 batches of samples， and 9 common peaks were identified. The similarity of samples was between 0.768-0.989， and the similarity of base and traditional medicinal part samples （S1-S10） were more than 0.970. The 21 batches of samples were clustered into 3 categories， in which S1-S10 were category Ⅰ； S15-S16， S19-S20 were category Ⅱ； other were category Ⅲ. By PLS-DA analysis， 11 classification markers were identified as well as 5 chromatogram peaks were identified， such as ferulic acid， pine cyperyl ferulate， n-butyl phthalide， ligustilide， ligustilide A， which could be used to distinguish base and non-markted samples （S1-S10） from marketed and non-base samples （S11-S21）， which were consistent with the results of cluster analysis. CONCLUSIONS： Established fingerprint， cluster analysis and PLS-DA analysis can provide reference for quality evaluation of L. chuanxiong decoction pieces.