Therapeutic potential of genipin in various acute liver injury, fulminant hepatitis, NAFLD and other non-cancer liver diseases: More friend than foe.

Genipin is an aglycone derived from the geniposide, the most abundant iridoid glucoside constituent of Gardenia jasminoides Ellis. For decades, genipin is the focus of studies as a versatile compound in the treatment of various pathogenic conditions. In particularly, Gardenia jasminoides Ellis has long been used in traditional Chinese medicine for the prevention and treatment of liver disease. Mounting experimental data has proved genipin possesses therapeutic potential for cholestatic, septic, ischemia/reperfusion-triggered acute liver injury, fulminant hepatitis and NAFLD. This critical review is a reflection on the valuable lessons from decades of research regarding pharmacological activities of genipin. Of note, genipin represents choleretic effect by potentiating bilirubin disposal and enhancement of genes in charge of the efflux of a number of organic anions. The anti-inflammatory capability of genipin is mediated by suppression of the production and function of pro-inflammatory cytokines and inflammasome. Moreover, genipin modulates various transcription factor and signal transduction pathway. Genipin appears to trigger the upregulation of several key genes encoding antioxidant and xenobiotic-metabolizing enzymes. Furthermore, the medicinal impact of genipin extends to modulation of regulated cell death, including autophagic cell death, apoptosis, necroptosis and pyroptosis, and modulation of quality of cellular organelle. Another crucial effect of genipin appears to be linked to dual role in targeting uncoupling protein 2 (UCP2). As a typical UCP2-inhibiting compound, genipin could inhibit AMP-activated protein kinase or NF-κB in circumstance. On the contrary, reactive oxygen species production and cellular lipid deposits mediated by genipin through the upregulation of UCP2 is observed in liver steatosis, suggesting the precise role of genipin is disease-specific. Collectively, we comprehensively summarize the mechanisms and pathways associated with the hepatoprotective activity of genipin and discuss potential toxic impact. Notably, our focus is the direct medicinal effect of genipin itself, whereas its utility as a crosslinking agent in tissue engineering is out of scope for the current review. Further studies are therefore required to disentangle these complicated pharmacological properties to confer this natural agent a far greater potency.

Preliminary study on high resolution mapping in human gastric electrical activities / 中华消化杂志

Objective To investigate the spatio-temporal characteristics of normal gastric electrical activity.Methods From January 1st to February 29th,2016,fasting gastric electric slow wave signal was collected by high resolution mapping (HRM) under anesthesia before operation in patients without gastric lesions but needed laparoscopic surgery.Parameters of slow wave signal activity was calculated,gastric activity map and velocities was drawn and then spatio-temporal characteristics of gastric electrical activity of different part of the stomach were obtained.Independent sample t test was performed for comparison of two groups and one-way analysis of variance was used for multiple group comparisons.Results The normal gastric pacing zone located in the upper middle part of gastric body near greater curvature.Electrical activity of gastric body spread to gastric antrum along the long axis of the stomach.No slow signal was recorded in the gastric fundus and the gastric cardia.The frequencies of slow waves of different parts of gastric was same and the mean value was 2.61 ±0.11 cycle per minute.Compared with that of gastric body,the slow wave amplitude of gastric pacing zone was higher ((4.19±0.73) mV vs (1.67± 0.89) mV) and the speed was faster (7.24± 1.37) mm/s vs (4.94± 0.20) mm/s);the differences were statistically significant (t=18.89 and 4.95,both P＜0.01).The slow wave amplitude of gastric antrum was higher than that of gastric body ((3.21±0.49) mV vs (1.67±0.89) mV) and the speed was also faster ((6.44±0.82) mm/s vs (4.94±0.20) mm/s);the differences were statistically significant (t=4.85 and 4.95,both P＜0.05).The slow wave amplitude of gastric antrum was lower than that of pacemaker area ((3.21±0.49) mV vs (4.19±0.73) mV),and the difference was statistically significant (t =-3.67,P＜0.05);however,there was no significant difference in wave velocity ((6.44±0.82) mm/s vs (7.24±1.37) mm/s,P＞0.05).Conclusions The normal human gastric pacemaker is located in mid and upper corpus near the greater curvature,which produces slow wave and control whole gastric electrical activity.The amplitude and velocity of slow waves are in gradient changes in different gastric regions.HRM is a mature and reliable research method to study the spatio-temporal characteristics of gastric electrical activity,which provides the possibility for the study of abnormal gastric electrical activity.

Preliminary study on high resolution mapping in human gastric electrical activities / 中华消化杂志

Objective To investigate the spatio-temporal characteristics of normal gastric electrical activity.Methods From January 1st to February 29th,2016,fasting gastric electric slow wave signal was collected by high resolution mapping (HRM) under anesthesia before operation in patients without gastric lesions but needed laparoscopic surgery.Parameters of slow wave signal activity was calculated,gastric activity map and velocities was drawn and then spatio-temporal characteristics of gastric electrical activity of different part of the stomach were obtained.Independent sample t test was performed for comparison of two groups and one-way analysis of variance was used for multiple group comparisons.Results The normal gastric pacing zone located in the upper middle part of gastric body near greater curvature.Electrical activity of gastric body spread to gastric antrum along the long axis of the stomach.No slow signal was recorded in the gastric fundus and the gastric cardia.The frequencies of slow waves of different parts of gastric was same and the mean value was 2.61 ±0.11 cycle per minute.Compared with that of gastric body,the slow wave amplitude of gastric pacing zone was higher ((4.19±0.73) mV vs (1.67± 0.89) mV) and the speed was faster (7.24± 1.37) mm/s vs (4.94± 0.20) mm/s);the differences were statistically significant (t=18.89 and 4.95,both P＜0.01).The slow wave amplitude of gastric antrum was higher than that of gastric body ((3.21±0.49) mV vs (1.67±0.89) mV) and the speed was also faster ((6.44±0.82) mm/s vs (4.94±0.20) mm/s);the differences were statistically significant (t=4.85 and 4.95,both P＜0.05).The slow wave amplitude of gastric antrum was lower than that of pacemaker area ((3.21±0.49) mV vs (4.19±0.73) mV),and the difference was statistically significant (t =-3.67,P＜0.05);however,there was no significant difference in wave velocity ((6.44±0.82) mm/s vs (7.24±1.37) mm/s,P＞0.05).Conclusions The normal human gastric pacemaker is located in mid and upper corpus near the greater curvature,which produces slow wave and control whole gastric electrical activity.The amplitude and velocity of slow waves are in gradient changes in different gastric regions.HRM is a mature and reliable research method to study the spatio-temporal characteristics of gastric electrical activity,which provides the possibility for the study of abnormal gastric electrical activity.

Advances in Management of Gastrointestinal Stromal Tumors with Secondary Resistance to Imatinib / 胃肠病学

The use of tyrosine kinase inhibitor imatinib in treatment of gastrointestinal stromal tumors(GISTs)has achieved a dramatic therapeutic efficacy. However,secondary imatinib resistance emerged as a clinical problem needs to be solved urgently. The underlying mechanisms of GISTs secondary resistance to imatinib may be related with secondary mutations of KIT/ PDGFRA genes,loss of PTEN gene and induction of cellular quiescence. This resulted in the adoption of new therapeutic strategies such as novel tyrosine kinase inhibitors,combined use of imatinib with downstream signaling inhibitors,KIT/ PDGFRA independent targeted inhibitors such as KIT chaperone inhibitors and aurora kinase inhibitors,as well as inducing apoptosis in quiescent GIST cells. In this article,the above-mentioned issues were summarized.

A Preliminary Study on Gastric Electrical Activity in Patients with Gastrointestinal Stromal Tumor / 天津医药

Objects: To investigate the behavior of gastric electrical activity in patients with gastrointestinal stromal tumor(GIST) to identify the influences of GIST on the normal gastric electrical activity. Methods: The electrogastrogram (EGG) parameters of 27 patients with gastric GIST (GIST group) and 30 healthy volunteers (control group) were detected by the multi-channel electrogastrogram and the data were analyzed. Results: The values of postprandial mean frequency (MF), mean amplitude (MA) and the percentage of normal slow wave (N%) were increased, and the percentage of bradygastria (B%) was decreased than those of the fasting in control group(P 0.05). Compared with control group, the fasting MF and MA increased, the fasting N% of lead 1, 3, 4 and postprandial N% decreased, both percentages of fasting and postprandial tachygastria (T%) increased in GIST group (P < 0.01). The tachygastria incidence was significantly higher in GIST group than that of control (66.7% vs 3.3%, P <0.05). Conclusion: The gastric electrical activity was affected by the existence of GIST. The abnormal gastric electrical rhythm displayed mainly as tachygastria.