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 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.

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.

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 evaluate the efficacy and safety of endoscopic anterior fundoplication by the MUSETM endoscopic stapling device in gastroesophageal reflux disease (GERD).Methods From March to November 2017,in the Department of Gastroenterology of Chinese PLA General Hospital in Beijing,The First People's Hospital Affiliated to Shanghai Jiao Tong University and Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,thirteen GERD patients who underwent the endoscopic anterior fundoplication by the MUSETM system were enrolled.The GERD health related quality of life questionnaire (GERD-HRQL) score,satisfaction of symptomatic control,questionnaire for gastroesophageal reflux disease (GERD-Q) score,the degree of esophagitis,condition of gastroesophageal flap valve,medicine administration and side effects were compared before and after the operation.Paired t test and Wilcoxon rank sum test were performed for statistical analysis.Results The total GERD-HRQL score decreased from 23 points (14 to 36 points) before operation when proton pump inhibitor (PPI) was stopped for seven days to 3 points (0 to 21 points) at three months after operation and 1 point (0 to 18 points) at six months after operation;and the differences were statistically significant (Z=-3.111 and -3.183,both P＜0.01).Among 13 patients,the GERD-HRQL score of 11 patients decreased over 50 ％ after operation.The heartburn score decreased from 21 points (13 to 29 points) before operation when PPI was stopped for seven days to 0 point (0 to 17 points) at three months after operation and 0 point (0 to 16 points) at six months after operation;and the differences were statistically significant (Z=-3.113 and -3.182,both P＜0.01).Among 13 patients,assessment of symptom control at three months after operation of seven patients were satisfactory,four patients were mostly satisfactory and two patients were unsatisfactory;assessment of symptom control at six months after operation of nine patients were satisfactory,four patients were mostly satisfactory;and the satisfaction rate were both higher than that before operation,and the differences were statistically significant (x2=16.235 and 25.159,both P＜0.01).The total GERD-Q score reduced from 13 points (8 to 17 points) before operation to 6 points (3 to 11 points) at three months after operation and 6 points (6 to 13 points) at six months after operation (Z=-3.192 and-3.066,both P＜0.01).DeMeester score decreased from 38.40 points (20.20 to 255.30 points) to 11.10 points (1.10 to 46.20 points) at six months after operation;and the percent of total time of esophageal pH＜4 reduced from 10％ (5％ to 75％) to 3％ (0 to 13％) at six months after operation;the difference was statistically significant (Z=-3.181 and-3.180,both P=0.001).There was no significant difference in esophageal motility changes before and after treatment (all P ＞ 0.05).The number of patients without esophagitis increased from three before treatment to eight after treatment.Additionally,the number of patients whose gastroesophageal flap valve was less than grade Ⅱ increased from three before operation to 11 at six months after operation.The patients were followed up for six months,among 13 patients,10 patients were completely deprived of PPI,one patient was reduced over 50％,and two patients were treated with less than 50％ reduction.All 13 patients had mild tolerable abdominal pain and sore throat within 48 hours after operation.No other adverse reactions were observed.Conclusion The endoscopic anterior fundoplication by the MUSETM is a safe and effective treatment for GERD.

To obtain specific antibodies against nsp4 protein of porcine reproductive and respiratory syndrome virus (PRRSV), nsp4 gene was amplified by RT-PCR and cloned into pET-28a(+) vector, designated pET28a-nsp4. pET28a-nsp4 was transformed into Escherichia coli Trasseta (DE3) cells and expressed after induction of IPTG. SDS-PAGE analysis showed that the recombinant protein was expressed in soluble form with the molecular weight of 26 kDa. The soluble fusion protein in the supernatant was purified using Ni+-NTA affinity chromatography. New Zealand rabbits were immunized by the purified nsp4 and anti-sera against nsp4 were obtained. The titer of polyclonal antibodies was about 106 and showed good specificity and sensitivity in the immunofluorescence assay and Western blotting analysis. The polyclonal antibodies also recognized native nsp4 form PRRSV infected Marc-145 cells, providing a useful tool in PRRSV replication mechanism study.