Wang F

Sedation, analgesia, and cardiorespiratory function in colonoscopy using midazolam combined with fentanyl or propofol

Background and aimsThe use of sedatives during colonoscopy remains controversial because of its safety concerns. We compared cardiorespiratory function and sedative and analgesic effects in sedative colonoscopy, using combinations of midazolam with either fentanyl or propofol.MethodsEligible patients (nu2009=u2009480) received 1.0–2.0xa0mg midazolam alone (nu2009=u2009160), midazolam combined with either 50–100xa0mg fentanyl intramuscularly (nu2009=u2009160), or 0.5–2.5xa0mg/kg propofol intravenously, as premedication for sedative colonoscopy. Pulse rate, blood pressure, and saturation of peripheral oxygen (SpO2) were monitored. Levels of sedation and analgesia were semi-quantitatively scored using visual analog scales, and amnesia profiles were qualitatively evaluated.ResultsCombining midazolam with either fentanyl or propofol resulted in acceptable sedative and analgesic effects compared to treatment with midazolam alone (Pu2009<u20090.001), with the combination with propofol giving more favorable results. More patients receiving the propofol combination became amnestic to the procedure than patients receiving the fentanyl combination. However, midazolam combined with propofol disturbed the pulse rate (Pu2009<u20090.05) and blood pressure (Pu2009<u20090.001) more significantly than a combination with fentanyl, or midazolam alone.ConclusionThe combination of midazolam with either fentanyl or propofol allowed patients to undergo colonoscopy under comparable sedative and analgesic conditions. The combination with fentanyl had a significantly lower effect on pulse rate and blood pressure. The combination with propofol produced superior amnestic effects.

Comparative genomic study of gastric epithelial cells co-cultured with Helicobacter pylori

AIMnTo identify genes potentially involved in Helicobacter pylori (H. pylori)-induced gastric carcinogenesis.nnnMETHODSnGES-1 cells were co-cultured with H. pylori strains isolated from patients with gastric carcinoma (GC, n = 10) or chronic gastritis (CG, n = 10) for in vitro proliferation and apoptosis assays to identify the most and least virulent strains. These two strains were cagA-genotyped and used for further in vivo carcinogenic virulence assays by infecting Mongolian gerbils for 52 wk, respectively; a broth free of H. pylori was lavaged as control. Genomic profiles of GES-1 cells co-cultured with the most and least virulent strains were determined by microarray analysis. The most differentially expressed genes were further verified using quantitative real-time polymerase chain reaction in GES-1 cells infected with the most and least virulent strains, and by immunohistochemistry in H. pylori positive CG, precancerous diseases, and GC biopsy specimens in an independent experiment.nnnRESULTSnGC-derived H. pylori strains induced a potent proliferative effect in GES-1 cells in co-culture, whereas CG-derived strains did not. The most (from a GC patient) and least (from a CG patient) virulent strains were cagA-positive and negative, respectively. At week 52, CG, atrophy, metaplasia, dysplasia, and GC were observed in 90.0%, 80.0%, 80.0%, 90%, and 60.0%, respectively, of the animals lavaged with the most virulent strain. However, only mild CG was observed in 90% of the animals lavaged with the least virulent strain. On microarray analysis, 800 differentially expressed genes (49 up- and 751 down-regulated), involving those associated with cell cycle regulation, cell apoptosis, cytoskeleton, immune response, and substance and energy metabolisms, were identified in cells co-cultured with the most virulent strain as compared with those co-cultured with the least virulent strain. The six most differentially expressed genes (with a betweenness centrality of 0.1-0.2) were identified among the significant differential gene profile network, including JUN, KRAS, BRCA1, SMAD2, TRAF1, and HDAC6. Quantitative real-time polymerase chain reaction analyses verified that HDAC6 and TRFA1 mRNA expressions were significantly more up-regulated in GES-1 cells co-cultured with the most virulent strain than in those co-cultured with the least virulent strain. Immunohistochemistry of gastric mucosal specimens from H. pylori-positive patients with CG, intestinal metaplasia (IM), dysplasia, and GC showed that moderately positive and strongly positive HDAC6 expression was detected in 21.7% of CG patients, 30.0% of IM patients, 54.5% of dysplasia patients, and 77.8% of GC patients (P < 0.001). The up-regulation of TRAF1 expressions was detected in 34.8%, 53.3%, 72.7%, and 88.9% specimens of CG, IM, dysplasia, and GC, respectively (P < 0.001).nnnCONCLUSIONnThe overexpression of HDAC6 and TRAF1 in GES-1 cells co-cultured with the GC-derived strain and in H. pylori-positive dysplasia and GC suggests that HDAC6 and TRAF1 may be involved in H. pylori-induced gastric carcinogenesis.

Association between Virulence Factors and TRAF1/4-1BB/Bcl-xL Expression in Gastric Mucosa Infected with Helicobacter pylori

Objective. CagA+/vacAs1+/vacAm1+ Helicobacter pylori upregulates the expression of tumor necrosis factor receptor–associated factor 1 (TRAF1), tumor necrosis factor receptor superfamily member 9 (4-1BB), and B-cell lymphoma-extra large (Bcl-xL) in human gastric epithelial cells. We investigated the correlation between cagA/vacAs1/vacAm1 and TRAF1/4-1BB/Bcl-xL expression in gastric mucosal tissue of patients with gastric disorders. Methods. We collected gastric mucosa samples from 35 chronic, nonatrophic gastritis (CG) patients, 41 atrophic gastritis patients, 44 intestinal metaplasia with atypical hyperplasia (IM) patients, and 28 gastric carcinoma (Ca) patients. The expression ofu2009u2009TRAF1, 4-1BB, and Bcl-xL was determined using western blotting. The expression of cagA, vacAs1, and vacAm1 in H. pylori was examined with polymerase chain reaction. Results. The expression of TRAF1, 4-1BB, and Bcl-xL was significantly upregulated in IM and Ca patients (P < 0.05 compared with CG). There were more cases of cagA+/vacAs1+/vacAm1+ H. pylori infection in samples with elevated TRAF1, 4-1BB, or Bcl-xL expression (P < 0.05). Additionally, there were a remarkably large number of samples with upregulated TRAF1/4-1BB/Bcl-xL expression in cases of cagA+/vacAs1+/vacAm1+ H. pylori infection (44 cases, 67.7%; P < 0.05). Conclusions. The pathogenesis of IM and Ca may be promoted by cagA+/vacAs1+/vacAm1+ H. pylori, possibly via upregulated TRAF1, 4-1BB, and Bcl-xL in gastric mucosal tissue.

The expression level of TRAF1 in human gastric mucosa is related to virulence genotypes of Helicobacter pylori

Abstract Objective. To investigate the expression level of tumor necrosis factor receptor-associated factor 1 (TRAF1) in gastric mucosa tissue in patients infected with Helicobacter pylori (H. pylori) and to analyze the relationship between TRAF1 expression and H. pylori virulence. Methods. Gastric tissue samples were collected from patients with gastritis, atrophic gastritis, intestinal metaplasia with atypical hyperplasia, and gastric cancer. The expression level of TRAF1 in each group was analyzed by real-time polymerase chain reaction (PCR) and Western blot analysis. Virulence genotypes of H. pylori were determined by PCR. Results. Significant differences in TRAF1 mRNA levels were observed between the gastritis and gastric cancer groups, and the atrophic gastritis and gastric cancer groups (p < 0.05). Moreover, significant differences in TRAF1 protein levels were observed between the gastritis and intestinal metaplasia with atypical hyperplasia groups, between the gastritis and gastric cancer groups, and between the atrophic gastritis and gastric cancer groups (all p < 0.05). The virulence genotypes of cytotoxin-associated gene A (cagA), vacAs1, and vacAm1 were more frequent in the TRAF1 high-level group than in the TRAF1 low-level group (p < 0.05). Conclusion. Higher TARF1 expression level is associated with infection by CagA+/vacAs1+/m1+ virulent H. pylori strains and may promote the proliferation of gastric mucosal cells and induce gastric cancer.

Stepwise sedation for elderly patients with mild/moderate COPD during upper gastrointestinal endoscopy

AIMnTo investigate stepwise sedation for elderly patients with mild/moderate chronic obstructive pulmonary disease (COPD) during upper gastrointestinal (GI) endoscopy.nnnMETHODSnEighty-six elderly patients with mild/moderate COPD and 82 elderly patients without COPD scheduled for upper GI endoscopy were randomly assigned to receive one of the following two sedation methods: stepwise sedation involving three-stage administration of propofol combined with midazolam [COPD with stepwise sedation (group Cs), and non-COPD with stepwise sedation (group Ns)] or continuous sedation involving continuous administration of propofol combined with midazolam [COPD with continuous sedation (group Cc), and non-COPD with continuous sedation (group Nc)]. Saturation of peripheral oxygen (SpO2), blood pressure, and pulse rate were monitored, and patient discomfort, adverse events, drugs dosage, and recovery time were recorded.nnnRESULTSnAll endoscopies were completed successfully. The occurrences of hypoxemia in groups Cs, Cc, Ns, and Nc were 4 (9.3%), 12 (27.9%), 3 (7.3%), and 5 (12.2%), respectively. The occurrence of hypoxemia in group Cs was significantly lower than that in group Cc (P < 0.05). The average decreases in value of SpO2, systolic blood pressure, and diastolic blood pressure in group Cs were significantly lower than those in group Cc. Additionally, propofol dosage and overall rate of adverse events in group Cs were lower than those in group Cc. Finally, the recovery time in group Cs was significantly shorter than that in group Cc, and that in group Ns was significantly shorter than that in group Nc (P < 0.001).nnnCONCLUSIONnThe stepwise sedation method is effective and safer than the continuous sedation method for elderly patients with mild/moderate COPD during upper GI endoscopy.

Effects of different types of Helicobacter pylori on the gap junction intercellular communication in GES-1 cells

OBJECTIVEnTo determine the effect of different types of Helicobacter pylori (H.pylori) on the gap junction intercellular communication (GJIC) in GES-1 cells, and investigate the types of H.pylori related to the dysfunction of GJIC.nnnMETHODSnDifferent types of H.pylori clinical strains were isolated and cultured, including the East Asian CagA(-)positive H.pylori (East Asian CagA(+)H.pylori), Western CagA(-)positive H.pylori (Western CagA(+)H.pylori), and the CagA(-)negative H.pylori (CagA(-)H.pylori). We co-cultured these H.pylori strains with GES-1 cells for 24 and 48 h, respectively. The control group was cultured without any H.pylori for 24 and 48 h. Change of the GJIC function in GES-1 cells was detected by the scrape-loading dye transfer (SLDT) technique. The cell proliferation of each group was examined by the methyl thiazolyl tetrazolium bromide (MTT) assay.nnnRESULTSnThe control group showed better GJIC function in the GES-1 cells, and the fluorescent dye migrated 4-5 rows to the adjacent cells at 24 and 48 h. Compared with the control group, the GJIC function of GES-1 cells in the CagA(-)H.pylori group decreased and the fluorescent dye migrated 3 rows to the adjacent cells. Compared with the control group and the CagA(-) H.pylori group, the GJIC function of GES-1 cells in the Western CagA(+)H.pylori group decreased and the fluorescent dye migrated 1-2 rows to the adjacent cells. The East Asian CagA(+)H.pylori group showed no GJIC function or weak GJIC function, and most of the fluorescent dye was confined to the area of scratched single row cells and only a few migrated 1-2 rows to the adjacent cells. Difference in the cell proliferation between the CagA(-)H.pylori group and the control group was not significant. The cell proliferation of the Western CagA(+)H.pylori group and the East Asian CagA(+)H.pylori group at bacterium-to-cell ratio of 100:1 and 200:1 was higher than that of the control group. The cell prolife-ration of the East Asian CagA(+)H.pylori group at bacterium-to-cell ratio of 400:1 was significantly lower than that of the control group at 48 h.nnnCONCLUSIONnH.pylori can inhibit the GJIC function in GES-1 cells, which may be associated with CagA(+)H.pylori, especially with East Asian CagA(+)H.pylori. The effect of H.pylori on the proliferation of GES-1 cells is related to virulence factor CagA.

Correlation between the cystathionine-r-lyase (CES) and the severity of peptic ulcer disease

BACKGROUNDnThe infection of Helicobacter pylori (H. pylori) is one of the most important causes of gastric ulcer disease. The role of hydrogen sulfide (H2S) production in H. pylori-induced gastric ulcer disease.nnnAIMnThe expression of cystathionine-γ-lyase (CSE) was determined, and correlated with the severity of gastric ulcer disease.nnnMETHODSnOne hundred and eight patients were selected based on the determination of gastric ulcer and the infection of Helicobacter pylori (H. pylori), including 36 normal control, 36 patients with H. Pylori-negative gastric ulcer, and 36 patients with H. Pylori-positive gastric ulcer. RT-PCR determination was performed to determine the expression of CSE, NF-κB and IL-8.nnnRESULTSnThe expression of CSE, NF-κB and IL-8 was higher in the gastric ulcer group than control group (p<0.05). Compared with the H. pylori-negative gastric ulcer, the expression of CSE, NF-κB and IL-8 was higher than H. pylori-positive gastric ulcer group (p<0.05). For H. pylori-negative gastric ulcer group, the expression of CSE positively correlated with the expression of NF-κB (r=0.98, p<0.05) and IL-8 (r=0.95, p<0.05). For H. pylori-positive gastric ulcer group, the expression of CSE also positively correlated with the expression of NF-κB (r=0.99, p<0.05) and IL-8 (r=0.85, p<0.05).nnnCONCLUSIONnThe expression of CSE was positively correlated with the severity of gastric ulcer.

Chronic Helicobacter pylori infection induces the proliferation and apoptosis in gastric epithelial cells and gastric precancerosis in Mongolian gerbils

OBJECTIVEnTo explore the effect of different Helicobacter pylori (H.pylori) clinical strains on the proliferation and apoptosis of gastric epithelial cells, and to observe the effect of H.pylori on gastric mucosa by Mongolian gerbil model infected H.pylori.nnnMETHODSnH.pylori isolates harvested from pathologically documented gastric carcinoma (GC, n=10) or chronic gastritis specimens (CG, n=10) were co-cultured with GES-1 cells individually. MTT assay and flow cytometry were used to determine the proliferation and apoptosis of GES-1 cells induced by H.pylori isolates. Mongolian gerbils were infected by the most (A strain) and the least (B strain) significantly proliferated H.pylori strains. Results When co-cultured with the cell/bacteria concentration ratio 1:1 and 1:50 for 12 h and the cell/bacteria concentration ratio 1:50 for 24 h, H.pylori clinical strains isolated from patients with gastric cancer promoted the proliferation of GES-1 cells, and there was significant difference in the absorbance compared with the group of gastritis strains(P<0.05). The apoptosis rate of the GC and CG groups increased significantly (P<0.05) compared with the control group when co-cultured with the cell/bacteria concentration ratio 1:50 and 1:200, and there was no significant difference between the GC group and the CG group (P>0.05). The incidences of intestinal metaplasia and dysplasia in the A strain group were significantly higher than those in the B strain group (P<0.05).nnnCONCLUSIONnH.pylori strains from different disease sources have different effects on the proliferation of GES-1 cells. H.pylori isolated from gastric cancer can promote the proliferation of cells to different degrees and directly induce gastric precancerosis and gastric cancer.

Efficacy and security of sedation in upper gastrointestinal endoscopy in snoring patients

OBJECTIVEnTo investigate the efficacy and security of different administrations of propofol on the sedation in upper gastrointestinal endoscopic procedures in snoring patients.nnnMETHODSnA total of 1,117 patients with snoring in ASA I-II level, who underwent gastroscopy and received propofol as sedation, were assigned to Group A, Group B, and Group C.These groups had different administration methods of propofol. The dose of propofol, response to endoscopic procedures, changes of oxygen saturation of arterial blood (SPO₂), incidence of severe respiratory depression and sedation quality assessed by operators were observed.nnnRESULTSnThe incidence of transient decline in SPO₂ in Group A, B, and C were 50.4%, 3.1%, and 18.5%, respectively. The doses of propofol of Group A, B, and C were (108.50±18.02) mg, (57.50±7.50) mg, and (79.80±10.02) mg, respectively, with significant difference (P<0.05). The incidence of severe respiratory depression in Group A was 1.2%, but Group B and C were 0%. Compared with Group A(100%) and C(100%), the satisfaction rate of sedation quality in Group B was 74%, with significant difference (P<0.05).nnnCONCLUSIONnDuring the upper gastrointestinal endoscopic procedures, snoring patients are premedicated with propofol in various uses by steps or one slow administration. Both methods are safe and effective to reduce the incidence of severe respiratory depression, and patients have no memory of the procedure.

Influence of age on sedation for colonoscopy in adults

OBJECTIVEnTo investigate the efficacy and risk of midazolam and propofol for sedation during colonoscopy procedures in adults of different age groups.nnnMETHODSnA total of 180 patients undergoing colonoscopy were allocated to 3 groups: a young adult group (n=45, 18-44 years), a mid-aged group (n=78,45-64 years) and an elderly group (n=57, 65-80 years). All patients were premedicated with midazolam 0.02-0.03 mg/kg and propofol 0.5-2.5 mg/kg. The pulse rate, arterial pressure, and oxygen saturation for each patient were monitored continuously before, during and after the procedure.nnnRESULTSnThe doses of midazolam and propofol for the young adults were significantly higher than that for the mid-aged and the elderly (P<0.01). Based on the view of gastroenterologists, the satisfied rate of sedation quality was significantly higher in the elderly group than that in the young or the mid-aged group (P<0.01). There were significant changes in the arterial pressure in all groups compared with the baseline level (P<0.01), but there was no significant difference among the 3 groups. Other parameters such as heart rate, saturation of O2, and the rate of severe adverse reaction among the 3 groups were not significantly different (P>0.05).nnnCONCLUSIONnHigher dose of midazolam and propofol is needed to obtain the sedation quality in young adults. Whereas for the elderly, properly reducing the dose of midazolam and propofol may still keep the sedation quality during colonoscopy procedures.