Background and Aims:Nonalcoholic fatty liver disease(NAFLD)is a common chronic liver disease caused by overnutrition.Impaired autophagy is closely related to NAFLD progression.Recently,ubiquitin-specific peptidase-10(...Background and Aims:Nonalcoholic fatty liver disease(NAFLD)is a common chronic liver disease caused by overnutrition.Impaired autophagy is closely related to NAFLD progression.Recently,ubiquitin-specific peptidase-10(USP10)was reported to ameliorate hepatic steatosis,but the underlying mechanism is still unclear.In view of the potential effects of USP10 on autophagy,we investigated whether USP10 alleviated steatosis through autophagy.Methods:HepG2 cells were treated with palmitic acid(PA)to model NAFLD in vitro.Lentivirus was used to regulate USP10 level in cells.Autophagic regulators were used to autophagic progression in cells.Western blotting,real-time fluorescence quantitative polymerase chain reaction,lipid drop staining and immunofluorescent staining were performed to determine the effect of USP10 on lipid autophagy.Student’s t-test and Tukey’s post hoc test were used to compare the means among groups.Results:PA induced cellular steatosis with dependance on autophagy.USP10 overexpression alleviated PA-induced steatosis,restored autophagic activity,promoted autophagic flux,including synthesis and degradation of autophagosomes,and lipid-targeted autophagy.In the presence of autophagy inhibitors,the protective effectiveness of USP10 on steatosis decreased.Furthermore,the specific inhibitor to C-jun N-terminal protein kinase-1(JNK1),DB07268,abolished USP10-induced autophagy.However,during early stage inhibition of JNK1,compensatory expression of tuberous sclerosis complex-2(TSC2)maintained autophagy.The degree of TSC2-to-JNK1 compensation was positively associated with USP10 level.Functionally,JNK1 and TSC2 were involved in the lipid-lowering effect of USP10.Conclusions:USP10 alleviated hepatocellular steatosis in autophagy-dependent manner.JNK1/TSC2 signaling pathways were required for USP10-induced autophagy.展开更多
Background： Nonanesthetic colonoscopy is popular in clinical practice in China. However, intestinal spasms often result in a prolonged examination time, increased operating difficulties, decreased polyp detection rat...Background： Nonanesthetic colonoscopy is popular in clinical practice in China. However, intestinal spasms often result in a prolonged examination time, increased operating difficulties, decreased polyp detection rate, and failure to complete the procedure clinically. Therefore, exploring alternative approaches that can reduce the pain in patients during colonoscopy is of utmost importance, and finding the optimal preoperative administration to improve the quality of nonanesthetic colonoscopy is also necessary. This study aimed to investigate the effects of the prophylactic administration of pinaverium bromide before colonoscopy and the effects of pinaverium bromide alone at different time points or combined with scopolamine butylbromide. Methods： A randomized controlled trial was performed on a cohort of 1000 patients who underwent colonoscopy in outpatient clinic of Wuhan Union Hospital. The patients were randomly assigned to the following groups： Group A, given oral pinaverium bromide （100 mg, three times a day） one day before examination combined with intramuscular injection of scopolamine butylbromide （20 mg） 10 min before colonoscopy; Group B0, given pinaverium bromide alone on the day ofcolonoscopy （ 100 mg, three times a day）; Group B1, given pinaverium bromide alone （100 mg, three times a day） one day before colonoscopy; Group B2, given pinaverium bromide alone （100 mg, three times a day） two days before colonoscopy; and Group C, given scopolamine butylbromide alone （20 mg） before colonoscopy. The successful rate of colonoscopy, procedure time, degree of abdominal pain, and polyp detection rate were recorded and compared among all groups. Results： The successful rate of colonoscopy in Group B1 （82.0%） and Group B2 （83.0%） was significantly higher than that in Group B1 （62.0%, all P 〈 0.01 ）. The time to reach the ileocecal region in Group B1 and Group B, were lower than those in Group B0 （all P 〈 0.05）. However, no significant differences were observed in polyp detection rate between Group B1（24.0%） or Group B2 （26.0%）, and Group Bo （22.4%, all P 〉 0.05）. Furthermore, there were no significant differences in the various parameters examined between Group B1 and Group B2 （P 〉 0.05）. The successful rate of colonoscopy in Group A （92.0%） was significantly higher than that in Group B2 （82.0%） and Group C （80.0%; both P 〈 0.05）. Moreover, the time for the colonoscope to reach the ileocecal region in Group A were markedly shorter as compared to those in Group B1 and Group C （P 〈 0.05）. The polyp detection rate in Group A was 32.0%, significantly higher than that in Group B1 （24.0%, P 〈 0.05） and Group C （24.2%, P 〈 0.05）. Conclusion： Administration of pinaverium bromide alone one day before examination was beneficial to relieve symptoms of abdominal pain during nonanesthetic colonoscopy. In addition, therapeutic effects were improved when pinaverium bromide administration was combined with intramuscular injection of scopolamine butylbromide. Therefore, the combined use ofpinaverium bromide with scopolamine butylbromide might have great application value to improve the quality of nonanesthetic colonoscopy in the preoperative preparation.展开更多
Objective:To analyze the efficacy and safety of moxibustion(A kind of complementary and alternative methods of traditional Chinese medicine)for the Functional dyspepsia(FD).Methods:Six electronic databases were search...Objective:To analyze the efficacy and safety of moxibustion(A kind of complementary and alternative methods of traditional Chinese medicine)for the Functional dyspepsia(FD).Methods:Six electronic databases were searched for randomized controlled trials investigating the efficacy of moxibustion in the treatment of FD.The search period was from inception to February 25,2019.Eligible reports of RCT on the moxibustion compare with medication were enrolled.Article's quality was evaluated with the Cochrane Risk Bias Tool in the Cochrane Handbook by two independent reviewers.The Review Manager 5.3 was used to evaluate the publication bias.Result:Eleven eligible reports comprising a total of 870 participants were enrolled.The risk of bias was generally high.In the primary outcome,compared with medications,moxibustion significantly alleviated overall FD symptoms but there was a moderate inconsistency among studies(11 RCTs,RR=1.27,95% CI[1.20,1.36]).Moxibustion appears to be associated with few adverse events but the evidence is limited due to poor report quality.Conclusion:Moxibustion showed greater improvement in terms of clinical efficacy in the treatment of FD than pharmacological medications,and although it was not possible to draw a definitive conclusion due to the small sample size,high risk of bias,and low quality of the reports.Large multi-center and long-term high-quality randomized control trials are needed.展开更多
Objective To determine whether high glucose enhances β-amyloid （Aβ） production in HEK293 Swedish mutant （APPsw） cells with Aβ precursor protein （APP） overexpression, and whether under this condition benfotiam...Objective To determine whether high glucose enhances β-amyloid （Aβ） production in HEK293 Swedish mutant （APPsw） cells with Aβ precursor protein （APP） overexpression, and whether under this condition benfotiamine reduces the increased Aβ production. Methods HEK293 APPsw cells were cultured with different concentrations of glucose for different times. TheAβ content in the supernatant was determined by ELISA. To investigate the mechanism by which benfotiamine reduced Aβ production, glycogen synthase kinase-3 （GSK-3） activity and expression were measured after the cells were cultured with 5.5 g/L glucose for 12 h. Results With 1.0, 3.0, 4.5, 5.5, 6.5, 7.5, 8.5, or 10.5 g/L glucose, Aβ production by HEK293 APPsw cells was highest in the presence of 5.5 g/L glucose for 6 and 12 h. The difference in Aβ content between 5.5 and 1.0 g/L was most marked after incubation for 12 h. Benfotiamine at 20 and 40 μg/mL significantly reduced Aβ production in cells incubated with 5.5 g/L glucose for 12 h. Moreover, 40 μg/mL benfotiamine significantly enhanced the ratio of phosphorylated GSK-3 to total GSK-3, together with consistent down-regulation of GSK-3 activity. Conclusion High glucose increases Aβ production by HEK293 APPsw cells while benfotiamine prevents this increase. This is correlated with the modulation of GSK-3 activity.展开更多
文摘Background and Aims:Nonalcoholic fatty liver disease(NAFLD)is a common chronic liver disease caused by overnutrition.Impaired autophagy is closely related to NAFLD progression.Recently,ubiquitin-specific peptidase-10(USP10)was reported to ameliorate hepatic steatosis,but the underlying mechanism is still unclear.In view of the potential effects of USP10 on autophagy,we investigated whether USP10 alleviated steatosis through autophagy.Methods:HepG2 cells were treated with palmitic acid(PA)to model NAFLD in vitro.Lentivirus was used to regulate USP10 level in cells.Autophagic regulators were used to autophagic progression in cells.Western blotting,real-time fluorescence quantitative polymerase chain reaction,lipid drop staining and immunofluorescent staining were performed to determine the effect of USP10 on lipid autophagy.Student’s t-test and Tukey’s post hoc test were used to compare the means among groups.Results:PA induced cellular steatosis with dependance on autophagy.USP10 overexpression alleviated PA-induced steatosis,restored autophagic activity,promoted autophagic flux,including synthesis and degradation of autophagosomes,and lipid-targeted autophagy.In the presence of autophagy inhibitors,the protective effectiveness of USP10 on steatosis decreased.Furthermore,the specific inhibitor to C-jun N-terminal protein kinase-1(JNK1),DB07268,abolished USP10-induced autophagy.However,during early stage inhibition of JNK1,compensatory expression of tuberous sclerosis complex-2(TSC2)maintained autophagy.The degree of TSC2-to-JNK1 compensation was positively associated with USP10 level.Functionally,JNK1 and TSC2 were involved in the lipid-lowering effect of USP10.Conclusions:USP10 alleviated hepatocellular steatosis in autophagy-dependent manner.JNK1/TSC2 signaling pathways were required for USP10-induced autophagy.
文摘Background： Nonanesthetic colonoscopy is popular in clinical practice in China. However, intestinal spasms often result in a prolonged examination time, increased operating difficulties, decreased polyp detection rate, and failure to complete the procedure clinically. Therefore, exploring alternative approaches that can reduce the pain in patients during colonoscopy is of utmost importance, and finding the optimal preoperative administration to improve the quality of nonanesthetic colonoscopy is also necessary. This study aimed to investigate the effects of the prophylactic administration of pinaverium bromide before colonoscopy and the effects of pinaverium bromide alone at different time points or combined with scopolamine butylbromide. Methods： A randomized controlled trial was performed on a cohort of 1000 patients who underwent colonoscopy in outpatient clinic of Wuhan Union Hospital. The patients were randomly assigned to the following groups： Group A, given oral pinaverium bromide （100 mg, three times a day） one day before examination combined with intramuscular injection of scopolamine butylbromide （20 mg） 10 min before colonoscopy; Group B0, given pinaverium bromide alone on the day ofcolonoscopy （ 100 mg, three times a day）; Group B1, given pinaverium bromide alone （100 mg, three times a day） one day before colonoscopy; Group B2, given pinaverium bromide alone （100 mg, three times a day） two days before colonoscopy; and Group C, given scopolamine butylbromide alone （20 mg） before colonoscopy. The successful rate of colonoscopy, procedure time, degree of abdominal pain, and polyp detection rate were recorded and compared among all groups. Results： The successful rate of colonoscopy in Group B1 （82.0%） and Group B2 （83.0%） was significantly higher than that in Group B1 （62.0%, all P 〈 0.01 ）. The time to reach the ileocecal region in Group B1 and Group B, were lower than those in Group B0 （all P 〈 0.05）. However, no significant differences were observed in polyp detection rate between Group B1（24.0%） or Group B2 （26.0%）, and Group Bo （22.4%, all P 〉 0.05）. Furthermore, there were no significant differences in the various parameters examined between Group B1 and Group B2 （P 〉 0.05）. The successful rate of colonoscopy in Group A （92.0%） was significantly higher than that in Group B2 （82.0%） and Group C （80.0%; both P 〈 0.05）. Moreover, the time for the colonoscope to reach the ileocecal region in Group A were markedly shorter as compared to those in Group B1 and Group C （P 〈 0.05）. The polyp detection rate in Group A was 32.0%, significantly higher than that in Group B1 （24.0%, P 〈 0.05） and Group C （24.2%, P 〈 0.05）. Conclusion： Administration of pinaverium bromide alone one day before examination was beneficial to relieve symptoms of abdominal pain during nonanesthetic colonoscopy. In addition, therapeutic effects were improved when pinaverium bromide administration was combined with intramuscular injection of scopolamine butylbromide. Therefore, the combined use ofpinaverium bromide with scopolamine butylbromide might have great application value to improve the quality of nonanesthetic colonoscopy in the preoperative preparation.
基金Supported by National Natural Science Foundation of China:81473790
文摘Objective:To analyze the efficacy and safety of moxibustion(A kind of complementary and alternative methods of traditional Chinese medicine)for the Functional dyspepsia(FD).Methods:Six electronic databases were searched for randomized controlled trials investigating the efficacy of moxibustion in the treatment of FD.The search period was from inception to February 25,2019.Eligible reports of RCT on the moxibustion compare with medication were enrolled.Article's quality was evaluated with the Cochrane Risk Bias Tool in the Cochrane Handbook by two independent reviewers.The Review Manager 5.3 was used to evaluate the publication bias.Result:Eleven eligible reports comprising a total of 870 participants were enrolled.The risk of bias was generally high.In the primary outcome,compared with medications,moxibustion significantly alleviated overall FD symptoms but there was a moderate inconsistency among studies(11 RCTs,RR=1.27,95% CI[1.20,1.36]).Moxibustion appears to be associated with few adverse events but the evidence is limited due to poor report quality.Conclusion:Moxibustion showed greater improvement in terms of clinical efficacy in the treatment of FD than pharmacological medications,and although it was not possible to draw a definitive conclusion due to the small sample size,high risk of bias,and low quality of the reports.Large multi-center and long-term high-quality randomized control trials are needed.
基金supported by grants from the National Natural Science Foundation of China(81071019)the International Cooperation Foundation of Shanghai Municipality, China (10430709600)the Outstanding Academic Leaders Foundation in Shanghai, China(11XD1401500)
文摘Objective To determine whether high glucose enhances β-amyloid （Aβ） production in HEK293 Swedish mutant （APPsw） cells with Aβ precursor protein （APP） overexpression, and whether under this condition benfotiamine reduces the increased Aβ production. Methods HEK293 APPsw cells were cultured with different concentrations of glucose for different times. TheAβ content in the supernatant was determined by ELISA. To investigate the mechanism by which benfotiamine reduced Aβ production, glycogen synthase kinase-3 （GSK-3） activity and expression were measured after the cells were cultured with 5.5 g/L glucose for 12 h. Results With 1.0, 3.0, 4.5, 5.5, 6.5, 7.5, 8.5, or 10.5 g/L glucose, Aβ production by HEK293 APPsw cells was highest in the presence of 5.5 g/L glucose for 6 and 12 h. The difference in Aβ content between 5.5 and 1.0 g/L was most marked after incubation for 12 h. Benfotiamine at 20 and 40 μg/mL significantly reduced Aβ production in cells incubated with 5.5 g/L glucose for 12 h. Moreover, 40 μg/mL benfotiamine significantly enhanced the ratio of phosphorylated GSK-3 to total GSK-3, together with consistent down-regulation of GSK-3 activity. Conclusion High glucose increases Aβ production by HEK293 APPsw cells while benfotiamine prevents this increase. This is correlated with the modulation of GSK-3 activity.
