In recent years,great progress has been achieved in the application of immune checkpoint inhibitors (ICI) in tumor immunotherapy.However,a variety of adverse reactions induced by ICI have been reported.Despite the high overall incidence of adverse reactions caused by ICI,some adverse reactions,such as immune-related pancreatitis,are rare in clinical practice.In this paper,a case of immune-related pancreatitis after treatment of advanced gastric cancer with nivolumab was identified.We analyzed the cause,treatment,incidence,and risk factors of the adverse reaction,aiming to improve the clinical diagnosis,treatment,and safe medication of rare adverse reactions associated with ICI.
Humans ; Nivolumab/adverse effects* ; Immune Checkpoint Inhibitors/adverse effects* ; Antineoplastic Agents, Immunological/adverse effects* ; Pancreatitis/drug therapy* ; Stomach Neoplasms

OBJECTIVE: To quantify phytochemicals using liquid chromatography and mass spectroscopy (LCMS) analysis and explore the therapeutic effect of Aesculus hippocastanum L. (AH) seeds ethanolic extract against gastric ulcers in rats. METHODS: Preliminary phytochemical testing and LCMS analysis were performed according to standard methods. For treatment, the animals were divided into 7 groups including normal control, ulcer control, self-healing, AH seeds low and high doses, ranitidine and per se groups. Rats were orally administered with 10 mg/kg of indomethacin, excluding the normal control group (which received 1% carboxy methyl cellulose) and the per se group (received 200 mg/kg AH seeds extract). The test group rats were then given 2 doses of AH seeds extract (100 and 200 mg/kg, respectively), while the standard group was given ranitidine (50 mg/kg). On the 11th day, rats in all groups were sacrificed, and their stomach was isolated to calculate the ulcer index, and other parameters such as blood prostaglandin (PGE₂), tissue superoxide dismutase (SOD), catalase (CAT), malonyldialdehyde (MDA), and glutathione (GSH). All isolated stomach tissues were analyzed for histopathological findings. RESULTS: The phytochemical examination shows that the AH seeds contain alkaloids, flavonoids, saponins, phenolic components, and glycosides. LCMS analysis confirms the presence of quercetin and rutin. The AH seeds extract showed significant improvement in gastric mucosa conditions after indomethacin-induced gastric lesions (P<0.01). Further marked improvement in blood PGE₂ and antioxidant enzymes, SOD, CAT, MDA and GSH, were observed compared with self-healing and untreated ulcer-induced groups (P<0.01). Histopathology results confirmed that AH seeds extract improved the mucosal layer and gastric epithelial membrane in treated groups compared to untreated ulcer-induced groups. CONCLUSIONS LCMS report confirms the presence of quercetin and rutin in AH seeds ethanolic extract. The therapeutic effect of AH seeds extract against indomethacin-induced ulcer in rat model indicated the regenerated membrane integrity, with improved cellular functions and mucus thickness. Further, improved antioxidant enzyme level would help to reduce PGE₂ biosynthesis.
Rats ; Animals ; Stomach Ulcer/pathology* ; Antioxidants/therapeutic use* ; Ranitidine/adverse effects* ; Aesculus ; Ulcer/drug therapy* ; Quercetin ; Plant Extracts/chemistry* ; Indomethacin/therapeutic use* ; Glutathione ; Superoxide Dismutase ; Rutin/adverse effects* ; Prostaglandins/adverse effects* ; Phytochemicals/therapeutic use*

Apoptosis/drug effects* ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Pentacyclic Triterpenes/pharmacology* ; Stomach Neoplasms/pathology*

To explore the mechanism of β-carboline alkaloids inhibiting the migration and invasion of SGC-7901 cells and its correlation with FAK gene expression,CCK-8 method was used to determine the inhibitory rate of β-carboline alkaloids on the proliferation of gastric cancer SGC-7901 cells under different concentrations.The effect of β-carboline alkaloids on the migration and invasion of SGC-7901 cells was used by Transwell compartment.Detection of mRNA and protein expression of FAK genes were used by qRT-PCR and Western blot.Then si-FAK-1051 recombinant plasmid was transfected into SGC-7901 cells.FAK gene silencing effect was identified by qRT-PCR and Western blot technique again.Finally,the effects of FAK gene silencing on proliferation and migration of gastric cancer SGC-7901 cells were detected by CCK-8 kit and Transwell chamber assay respectively.With the increase of the concentration ofβ-carboline alkaloids,the inhibitory rate of SGC-7901 cells in human gastric cancer cells increased gradually,with IC5013.364 mg·L-1.The number of SGC-7901 cells of Transwell compartment in the positive experimental group(5-FU,5 mg·L-1) and the β-carboline alkaloids group decreased significantly(P<0.01) and the number of SGC-7901 cells in the β-carboline alkaloids group was significantly lower than that in the positive experimental group(P<0.01).Compared with the blank control group,the mRNA and protein expression level of FAK genes in the positive experimental group was significantly lower than that in the experimental group of β-carboline alkaloids(P<0.05).After transfection of si-FAK-1051 into gastric cancer SGC-7901 cells,the expression of mRNA and protein of FAK gene was significantly down regulated(P<0.05).SGC-7901 cell proliferation and cell migration ability also decreased significantly(P<0.05).β-carboline alkaloids are more effective than 5-FU in inhibiting migration and invasion of gastric cancer SGC-7901 cells,and the mechanism may be related to the inhibition of mRNA and protein expression of FAK gene by β-carboline alkaloids.
Alkaloids ; pharmacology ; Carbolines ; pharmacology ; Cell Line, Tumor ; Cell Movement ; drug effects ; Cell Proliferation ; Focal Adhesion Kinase 1 ; genetics ; Gene Expression Regulation, Neoplastic ; Gene Silencing ; Humans ; Neoplasm Invasiveness ; Stomach Neoplasms ; drug therapy ; pathology

OBJECTIVE: To explore the pathogenesis of gastric cancer through a bioinformatic approach to provide evidence for the prevention and treatment of gastric cancer. METHODS: The differentially expressed genes (DEGs) in gastric cancer and normal gastric mucosa in GSE79973 dataset were analyzed using GEO2R online tool. GO analysis and KEGG pathway enrichment analysis of the DEGs in DAVID database were performed. The protein interaction network was constructed using STRING database, and the key genes (Hub genes) were screened and their functional modules were analyzed using Cytoscape software. The GEPIA database was used to validate the Hub genes, and the Target Scan database was used to predict the microRNAs that regulate the target genes; OncomiR was used to analyze the expressions of the microRNAs in gastric cancer tissues and their relationship with the survival outcomes of the patients. RESULTS: A total of 181 DEGs were identified in gastric cancer, and 10 hub genes were screened by the protein- protein interaction network. Functional analysis showed that these DEGs were involved mainly in protein digestion and absorption, PI3K-Akt signaling pathway, ECM-receptor interaction and platelet activation signal pathway. GEPIA database validation showed that COL1A1 was highly expressed in gastric cancer tissues and was associated with a poor prognosis of patients with gastric cancer. MiR-129-5p was found to bind to the 3'UTR of COL1A1 mRNA, and compared with that in normal tissues, miR-129-5p expression was obviously down-regulated in gastric cancer tissues, and was correlated with the prognosis of the patients. CONCLUSIONS COL1A1 under regulation by MiR-129-5p is a potential therapeutic target for gastric cancer.
Collagen Type I ; drug effects ; Computational Biology ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs ; therapeutic use ; Phosphatidylinositol 3-Kinases ; Stomach Neoplasms ; drug therapy

Resistance to cisplatin (DDP)-based chemotherapy is a major cause of treatment failure in human gastric cancer (GC). It is necessary to identify the drugs to re-sensitize GC cells to DDP. In our previous research, Zuo Jin Wan Formula (ZJW) has been proved could increase the mitochondrial apoptosis via cofilin-1 in a immortalized cell line, SGC-7901/DDP. Due to the immortalized cells may still difficult highly recapitulate the important molecular events in vivo, primary GC cells model derived from clinical patient was constructed in the present study to further evaluate the effect of ZJW and the underlying molecular mechanism. Immunofluorescent staining was used to indentify primary cultured human GC cells. Western blotting was carried out to detect the protein expression. Cell Counting Kit-8 (CCK-8) was used to evaluate cell proliferation. Flow cytometry analysis was performed to assess cell apoptosis. ZJW inhibited proliferation and induced apoptosis in primary DDP-resistant GC cells. Notably, the apoptosis in GC cells was mediated by inducing cofilin-1 mitochondrial translocation, down-regulating Bcl-2 and up-regulating Bax expression. Surprisingly, the level of p-AKT protein was higher in DDP-resistant GC cells than that of the DDP-sensitive GC cells, and the activation of AKT could attenuate ZJW-induced sensitivity to DDP. These data revealed that ZJW can increase the chemosensitivity in DDP-resistant primary GC cells by inducing mitochondrial apoptosis and AKT inactivation. The combining chemotherapy with ZJW may be an effective therapeutic strategy for GC chemoresistance patients.
Adult ; Aged ; Aged, 80 and over ; Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Cisplatin ; pharmacology ; therapeutic use ; Cofilin 1 ; metabolism ; Drug Resistance, Neoplasm ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Female ; Humans ; Male ; Middle Aged ; Mitochondria ; drug effects ; metabolism ; pathology ; Proto-Oncogene Proteins c-akt ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Stomach Neoplasms ; drug therapy ; metabolism ; pathology ; Tumor Cells, Cultured

The study analyzes the medication rules of Xin'an Wang's internal medicine for treating stomach cramps by data mining technology,in order to provide reference for clinical medication. Through the summarization of the medical cases of stomach cramps treated by Xin'an Wang's doctors( Wang Ren-zhi,Wang Zhong-qi,Wang Le-tao),statistics was made for the frequency of symptoms,signs,syndromes and drugs in Office 2010. Apriori algorithm in IBM SPSS Modeler 14. 1,and SPSS Statistics 22. 0 were used for association rule analysis and cluster analysis. The results showed that the 310 prescriptions collected involved totally 322 syndromes( including symptoms and signs) and 336 drugs,with the cumulative dose of 4 072 times; the symptoms were correlated to the spleen and stomach,liver and gallbladder,and the heart system; syndrome differentiation was mainly based on liver-Qi invasion of the stomach,diet impairment to the stomach,deficiency of spleen and stomach and cold syndrome; commonly used drugs were Qi regulating drugs,phlegm eliminating drugs and blood circulation promoting and stasis removing drugs; high-frequency drug complex network diagram showed that Pinelliae Rhizoma,Aurantii Fructus,Trichosanthis Fructus,Allii Macrostemonis Bulbus were closely related; the analysis showed 12,20,and 17 two,three,and four association rules; cluster analysis showed 10 pairs of Trichosanthis Fructus-Allii Macrostemonis Bulbus,Pinelliae Rhizoma-Aurantii Fructus,and Aspongopus-Toosendan Fructus drug combinations. According to Xin' an Wang's doctors,stomach cramps are closely related to liver and spleen,Qi stagnation,phlegm and blood stasis are the standard.Xin'an Wang's doctors give the first priority on " deoppilation",focus on soothing the liver and spleen,activating Qi and eliminating phlegm,and promoting blood circulation,and refer to use modified Xiaoxianxiong Decoction and modified Gualou Xiebai Banxia Decoction based on symptoms.
Data Mining ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Internal Medicine ; Medicine, Chinese Traditional ; Muscle Cramp/drug therapy* ; Qi ; Stomach/drug effects*

OBJECTIVEVigna subterranea is widely consumed as a traditional staple food in Nigeria and some West African countries. The ethanolic seed extract of V. subterranea (EEVS) was investigated for its gastroprotective effects on aspirin plus pylorus ligation-induced gastric ulcerated rats using an in vivo assay.

METHODSGastric mucosal ulceration was induced experimentally in Groups 2 to 5 using aspirin plus pylorus ligation. Rats in Group 1 were orally pretreated with 3% Tween 80 only as normal control. Groups 2 to 5 were pretreated with 3% Tween 80 (ulcer group), 20 mg/kg of omeprazole (positive group), and 200 and 400 mg/kg of EEVS (experimental groups), respectively, once daily for 21 days before ulcer induction. Parameters including those for gastric secretions, ulcerated areas and gastric wall histology were assessed. Levels of superoxide dismutase (SOD), glutathione peroxidase (GP), and malondialdehyde (MDA) in the gastric tissue homogenate were also determined.

RESULTSPretreatment with EEVS significantly (P < 0.05) reduced the ulcer index, gastric volume and total acidity in rats with aspirin plus pylorus ligation-induced ulcer. The pH and mucus of gastric content increased significantly (P < 0.05) while the levels of SOD and GP were observed to be elevated with a reduced amount of MDA. Significant severe gastric mucosal injury was exhibited in the ulcer group and EEVS or omeprazole offered significant (P < 0.05) protection against mucosal ulceration. Histologically, the gastric submucosal layer showed remarkable decrease in edema and leucocytes infiltration compared with ulcer group.

CONCLUSIONThe study suggests that EEVS offered a protective action against aspirin plus pylorus ligation-induced gastric ulcers in Wistar rats. The protective effect might be mediated via antisecretory, cytoprotective and antioxidative mechanisms.

Animals ; Anti-Ulcer Agents ; pharmacology ; therapeutic use ; Antioxidants ; pharmacology ; therapeutic use ; Aspirin ; Edema ; Gastric Mucosa ; drug effects ; metabolism ; pathology ; Gastrointestinal Agents ; pharmacology ; therapeutic use ; Glutathione Peroxidase ; metabolism ; Hydrogen-Ion Concentration ; Leukocytes ; Male ; Malondialdehyde ; metabolism ; Mucus ; metabolism ; Nuts ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; Rats, Wistar ; Severity of Illness Index ; Stomach Ulcer ; chemically induced ; drug therapy ; metabolism ; prevention & control ; Superoxide Dismutase ; metabolism ; Vigna

To summary and analyze the prescription rules of Professor Chen Baogui, a famous traditional Chinese medicine (TCM) doctor, for treating epigastric fullness. Professor Chen Baogui's prescriptions for treating epigastric fullness were collected and the treatment data were input into traditional Chinese medicine inheritance support system (TCMISS) to analyze the rules of the prescriptions by using data mining methods. Based on the screened 214 cases, the treatment experience of Professor Chen Baogui for treating epigastric fullness was summarized and analyzed. It was found that Professor Chen gave priority to recuperation of Qi activity. The results of four properties and five tastes showed Professor Chen's medication compatibility rules: one was simultaneous use of cold and warm drugs, and the other was simultaneous use of pungent drugs for dispersion and bitter drugs for purgation. In drug use, the basic prescriptions had the efficacy of promoting Qi circulation and regulating viscera function, additionally with the drugs with functions of eliminating digestion and inducing stagnation, activating blood circulation to dissipate blood stasis, replenishing Qi and nourishing Yin, tranquilizing mind, strengthening muscles and bones according to the TCM syndrome type. The clinical experience of Professor Chen for treating epigastric fullness was objectively summarized with the help of TCMISS, which was significant for analyzing and inheriting academic thinking and medication experience from famous TCM doctors.
Data Mining ; Digestion ; drug effects ; Drug Prescriptions ; standards ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Medicine, Chinese Traditional ; Stomach ; drug effects

OBJECTIVETo compare the postoperative analgesia efficacy, rehabilitation parameters and complication between multimodal analgesia and traditional analgesia after radical gastrectomy for gastric cancer patients.

METHODSPatients with gastric cancer who underwent surgery in our hospital from October 2016 to December 2016 were enrolled in this prospective study. According to the non-randomized method, patients were assigned to multimodal analgesia group(n=32) and traditional analgesia group(n=33) in gastric cancer treatment team A and B in Department of Gastrointestinal Surgery, West China Hospital, Sichuan University. The treatment measures of group A were as follows: (1) The ratio of 1/1 diluted ropivacaine (100 mg, 10 ml) was infiltrated around the incision before abdomen closure, with incision sutured layer by layer. (2) Parecoxib sodium (40 mg) was injected intravenously every 12 hours after operation for 5 days. (3) Oxycodone-acetaminophen tablet was given orally on the first day or the second day after operation, 50 mg twice a day. (4) Patient-controlled analgesia was not used after operation. Patients in group B received direct suture of incision and patient-controlled analgesia. The pain score, postoperative rehabilitation and 30-day postoperative complications were collected and analyzed.

RESULTSMultimodal analgesia group had lower pain scores at 1 d (4.8±0.9), 2 d (4.3±1.0), 3 d (2.9±0.8), 4 d (2.4±0.7) and 5 d (1.7±0.7) after surgery, as compared to traditional analgesia group (5.9±0.9, P=0.000), (5.1±0.7, P=0.001), (3.9±0.8, P=0.000), (3.0±0.6, P=0.000), (2.6±0.7, P=0.000), with significant difference. Postoperative hospital stay [(8.2±1.6) days vs. (10.6±2.2) days, P=0.000], time to ambulation [(47.5±13.8) days vs. (66.2±16.8) days, P=0.000], time to first flatus [(76.4±25.2) days vs. (120.0±29.9) days, P=0.000], time to first defecate [(117.3±42.2) days vs. (159.7±30.7) days, P=0.000] and time to first fluid diet [(83.8±21.6) days vs. (141.9±33.9) days, P=0.000] in the multimodal analgesia group were significantly shorter than those in the traditional analgesia group. There was no significant difference between the two groups with respect to 30-day postoperative complication rate(9.4% vs. 9.1%, P=1.000).

CONCLUSIONSMultimodal analgesia can significantly reduce the postoperative pain and is beneficial to rehabilitation, meanwhile it does not increase the risk of postoperative complications. Multimodal analgesia is safe and effective for gastric cancer patients undergoing radical gastrectomy.

Acetaminophen ; administration & dosage ; therapeutic use ; Amides ; administration & dosage ; therapeutic use ; Analgesia, Patient-Controlled ; China ; Comparative Effectiveness Research ; Defecation ; Drug Combinations ; Eating ; Flatulence ; Gastrectomy ; rehabilitation ; Humans ; Isoxazoles ; administration & dosage ; therapeutic use ; Length of Stay ; statistics & numerical data ; Oxycodone ; administration & dosage ; therapeutic use ; Pain Management ; methods ; Pain, Postoperative ; drug therapy ; Postoperative Complications ; Prospective Studies ; Recovery of Function ; drug effects ; Stomach Neoplasms ; surgery ; Surgical Wound ; rehabilitation ; therapy ; Suture Techniques ; Treatment Outcome ; Walking