Comparison of different gastric bypass procedures in gastric carcinoma patients with type 2 diabetes mellitus

AIM: To determine the effect of different Roux-en-Y gastric bypass procedures in gastric carcinoma patients with type 2 diabetes mellitus.METHODS: A retrospective analysis of the clinical data of 54 patients with gastric cancer and type 2 diabetes mellitus treated in the Department of General Surgery from January 2006 to June 2013 was conducted. The patients underwent gastrectomy using different Roux-en-Y gastric bypass procedures (traditional, n = 26; modified, n = 28). Fasting plasma glucose (FPG), two hour postprandial blood glucose (2 h PBG) and hemoglobin A1c (HbA1c) were analyzed before surgery (0 mo) and 1, 3 and 6 mo after surgery.RESULTS: FPG and 2 h PBG levels were significantly decreased 1 mo after surgery in the traditional Roux-en-Y gastric bypass group (FPG 7.5 ± 1.3 vs 10.7 ± 1.2, P < 0.05) (2 h PBG 10.2 ± 1.8 vs 13.8 ± 3.2, P < 0.05). FPG and 2 h PBG levels were significantly decreased after surgery in the modified Roux-en-Y gastric bypass group (FPG 6.9 ± 1.2 vs 10.5 ± 1.1, 6.5 ± 1.3 vs 10.5 ± 1.1, 6.4 ± 1.2 vs 10.5 ± 1.1, P < 0.05) (2 h PBG 9.9 ± 2.2 vs 14.1 ± 2.9, 9.2 ± 2.4 vs 14.1 ± 2.9, 8.9 ± 2.6 vs 14.1 ± 2.9, P < 0.05). Compared with the levels before surgery, HbA1c levels were significantly decreased 3 and 6 mo after surgery (7.2 ± 1.1 vs 10.5 ± 1.1, 5.5 ± 1.1 vs 10.5 ± 1.1, P < 0.05). Significant differences between the two groups regarding FPG, 2 h PBG and HbA1c concentration were observed 3 and 6 mo after surgery (FPG 10.1 ± 1.5 vs 6.5 ± 1.3, 10.3 ± 1.4 vs 6.4 ± 1.2, P < 0.05) (2 h PBG 13.1 ± 2.8 vs 9.2 ± 2.4, 13.6 ± 3.1 vs 8.9 ± 2.6, P < 0.05) (HbA1c 10.1 ± 1.4 vs 7.2 ± 1.1, 10.5 ± 1.3 vs 5.5 ± 1.1, P < 0.05).CONCLUSION: Modified Roux-en-Y gastric bypass can improve glucose metabolism in type 2 diabetic patients with gastric cancer.     

Association of caveolin-3 and cholecystokinin A receptor with cholesterol gallstone disease in mice

AIM: To investigate the role of caveolin-3 (CAV3) and cholecystokinin A receptor (CCKAR) in cholesterol gallstone disease (CGD).METHODS: To establish a mouse model of CGD, male C57BL/6 mice were fed with a lithogenic diet containing 1.0% cholic acid, 1.25% cholesterol and 15% fat; a similar control group was given a normal diet. The fresh liver weights and liver-to-body weight ratio were compared between the two groups after one month. Serum lipid profile and bile composition were determined with an autoanalyzer. The Cav3 and Cckar mRNA and CAV3 and CCKAR protein levels in the liver and gallbladder were determined via real-time polymerase chain reaction and Western blot, respectively.RESULTS: Establishment of the mouse CGD model was verified by the presence of cholesterol gallstones in mice fed the lithogenic diet. Compared with mice maintained on a normal diet, those fed the lithogenic diet had significantly higher mean liver-to-body weight ratio (0.067 ± 0.007 vs 0.039 ± 0.007, P < 0.01), serum total cholesterol (4.22 ± 0.46 mmol/L vs 2.21 ± 0.11 mmol/L, P < 0.001), bile total cholesterol (1.33 ± 0.33 mmol/L vs 0.21 ± 0.11 mmol/L, P < 0.001), and bile phospholipid concentrations (3.55 ± 1.40 mmol/L vs 1.55 ± 0.63 mmol/L, P = 0.04), but lower total bile acid concentrations (726.48 ± 51.83 μmol/L vs 839.83 ± 23.74 μmol/L, P = 0.007). The lithogenic diet was also associated with significantly lower CAV3 in the liver and lower CAV3 and CCKAR in the gallbladder compared with the control mice (all P < 0.05).CONCLUSION: CAV3 and CCKAR may be involved in cholesterol gallstone disease.     

Remote ischemic postconditioning protects against gastric mucosal lesions in rats

AIM: To investigate the protective effects of remote ischemic postconditioning (RIP) against limb ischemia-reperfusion (IR)-induced gastric mucosal injury.METHODS: Gastric IR was established in male Wistar rats by placing an elastic rubber band under a pressure of 290-310 mmHg on the proximal part of both lower limbs for 3 h followed by reperfusion for 0, 1, 3, 6, 12 or 24 h. RIP was performed using three cycles of 30 s of reperfusion and 30 s of reocclusion of the femoral aortic immediately after IR and before reperfusion for up to 24 h. Rats were randomly assigned to receive IR (n = 36), IR followed by RIP (n = 36), or sham treatment (n = 36). Gastric tissue samples were collected from six animals in each group at each timepoint and processed to determine levels of malondialdehyde (MDA), superoxide dismutase (SOD), xanthine oxidase (XOD) and myeloperoxidase (MPO). Additional samples were processed for histologic analysis by hematoxylin and eosin staining. Blood samples were similarly collected to determine serum levels of lactate dehydrogenase (LDH), creatine kinase (CK), tumor necrosis factor (TNF)-α and interleukin (IL)-10.RESULTS: The pathologic changes in gastric tissue induced by IR were observed by light microscopy. Administration of RIP dramatically reduced the gastric damage score after 6 h of reperfusion (5.85 ± 0.22 vs 7.72 ± 0.43; P < 0.01). In addition, RIP treatment decreased the serum activities of LDH (3.31 ± 0.32 vs 6.46 ± 0.03; P < 0.01), CK (1.94 ± 0.20 vs 4.54 ± 0.19; P < 0.01) and the concentration of TNF-α (53.82 ± 0.85 vs 88.50 ± 3.08; P < 0.01), and elevated the concentration of IL-10 (101.46 ± 5.08 vs 99.77 ± 4.32; P < 0.01) induced by IR at 6 h. Furthermore, RIP treatment prevented the marked elevation in MDA (3.79 ± 0.29 vs 6.39 ± 0.81) content, XOD (7.81 ± 0.75 vs 10.37 ± 2.47) and MPO (0.47 ± 0.05 vs 0.82 ± 0.03) activities, and decrease in SOD (4.95 ± 0.32 vs 3.41 ± 0.38; P < 0.01) activity in the gastric tissue as measured at 6 h.CONCLUSION: RIP provides effective functional protection and prevents cell injury to gastric tissue induced by limb IR via anti-inflammatory and antioxidant actions.     

Mechanical ventilation modulates Toll-like receptors 2, 4, and 9 on alveolar macrophages in a ventilator-induced lung injury model

Objective

To investigate the role of Toll-like receptor 2 (TLR2), TLR4, TLR9 and myeloid differentiation factor 88 (MyD88) on alveolar macrophages in ventilator-induced lung injury (VILI).

Methods

Male, adult pathogen-free Sprague-Dawley rats weighing 300-350 g were used in this study. Animals were tracheotomized and allowed to breathe spontaneously for 4 h or mechanically ventilated for 4 h with low or high tidal volume (7 or 40 mL/kg). TLR2, TLR4, and TLR9, MyD-88 and NF-κΒ of alveolar macrophages’ expression under the different ventilation conditions were detected. Pulmonary permeability, lung inflammatory, IL-6 and IL-1β were assessed as well.

Results

Rats subjected to high tidal volume showed significantly greater pulmonary permeability and lung inflammatory than the control rats. Alveolar macrophages from rats subjected to high tidal volume also showed significantly higher protein expression of TLR2 (0.59±0.049 vs. 0.35±0.036 and 0.36±0.031, both P<0.001), TLR4 (0.845±0.0395 vs. 0.401±0.026 and 0.403±0.020, both P<0.001), TLR9 (0.727±0.074 vs. 0.383±0.039 and 0.367±0.043, both P<0.001), MyD-88 (1.01±0.060 vs. 0.485±0.045 and 0.507±0.046, both P<0.001) and NF-κΒ (0.776±0.067 vs. 0.448±0.043 and 0.481±0.047, both P<0.001), as well as significantly higher concentrations of IL-6 (7.32±0.24 vs. 2.42±0.13 and 2.44±0.32, both P<0.001) and IL-1β (139.95±9.37 vs. 53.63±5.26 and 53.55±6.63, both P<0.001) than the control and low tidal volume group.

Conclusions

The overexpression of TLR2, TLR4, and TLR9 on alveolar macrophages and release of pro-inflammatory cytokines play a role in VILI.     

Tumor necrosis factor-α and interleukin-6 in cirrhotic patients with spontaneous bacterial peritonitis

AIM: To evaluate the role of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in cirrhotic patients who have hepatic and renal impairment with spontaneous bacterial peritonitis (SBP).METHODS: We prospectively studied 120 cirrhotic patients with SBP and 80 cirrhotic patients with sterile ascitic fluid. They included 144 males and 56 females with ages ranging between 34 and 62 years. The diagnosis of cirrhosis was established by clinical and laboratory criteria that did not require histological confirmation. The severity of underlying liver disease was evaluated using Pugh’s modification of Child’s criteria (Child-Pugh scores). Ascitic fluid was sent to the laboratory for cell count, culture, sensitivity testing, and measurement of chemical elements (i.e., albumin, glucose). Specimens were inoculated into aerobic and anaerobic blood culture bottles. Serum and ascitic fluid were also collected in sterile tubes at study entry (before the initiation of antibiotic treatment) and 48 h later. Assays for TNF-α and IL-6 in the serum and ascitic fluid were performed with an immunoenzymometric assay using manufacture’s instructions.RESULTS: Cytokine levels in serum and ascitic fluid were significantly higher in the patients with SBP. (plasma TNF-α: 135.35 ng/mL ± 11.21 ng/mL vs 92.86 ng/mL ± 17.56 ng/mL, P < 0.001; plasma IL-6: 32.30 pg/mL ± 7.07 pg/mL vs 12.11 pg/mL ± 6.53 pg/mL, P < 0.001; ascitic fluid TNF-α: 647.54 ± 107.11 ng/mL vs 238.43 ng/mL ± 65.42 ng/mL, P < 0.001); ascitic fluid IL-6: 132.84 ng/mL ± 34.13 vs 40.41 ± 12.85 pg/mL, P < 0.001). About 48 (40%) cirrhotic patients with SBP developed renal and hepatic impairment and showed significantly higher plasma and ascitic fluid cytokine levels at diagnosis of infection. [(plasma TNF-α: 176.58 ± 17.84 vs 135.35 ± 11.21 ng/mL) (P < 0.001) and (IL-6: 57.83 ± 7.85 vs 32.30 ± 7.07 pg/mL) (P < 0.001); ascitic fluid TNF-α: 958.39 ± 135.72 vs 647.54 ± 107.11 ng/mL, (P < 0.001), ascitic fluid IL-6: 654.74 ± 97.43 vs 132.84 ± 34.13 pg/mL, (P < 0.001)]. Twenty nine patients (60.4%) with SBP and renal impairment died whereas, only four patients (5.55%) with SBP but without renal impairment died from gastrointestinal hemorrhage (P < 0.0005).CONCLUSION: It appears that TNF-α production may enhance liver cell injury and lead to renal impairment. This correlated well with the poor prognosis and significantly increased mortality associated with SBP in cirrhotic patients.     

Clinical presentations of gastric small gastrointestinal stromal tumors mimics functional dyspepsia symptoms

AIM: To explore whether clinical presentations of gastric small gastrointestinal tumors (GISTs) mimics gastrointestinal dyspepsia symptoms.METHODS: The endosonographic data of 167 patients who underwent endoscopic submucosal dissection at the Tianjin Medical University General Hospital, China between 2009 and 2011 were analyzed. GISTs and leiomyomas had a similar intragastric distribution and similar locations within the gastric wall. Therefore, patients with GISTs were chosen as the study group and those with leiomyomas were chosen as the control group. Dyspepsia symptom questionnaires were used to investigate and compare the gastrointestinal symptoms of patients with GISTs and those with gastric leiomyomas before and after endoscopic submucosal dissection (ESD). The questionnaires evaluated symptoms such as epigastric pain, heartburn, regurgitation, epigastric discomfort, nausea and vomiting, abdominal bloating, and eructation. Symptoms were assessed using a four-point scoring scale.RESULTS: GISTs were the most common gastric submucosal lesion (67 cases, 40.12%), followed by leiomyomas (38 cases, 22.75%). Both groups were similar in terms of gender distribution (P = 0.49), intragastric location (P = 0.525), and originating layer within the gastric wall (P = 0.449), but leiomyomas were more commonly found in the proximal fundus (P < 0.05). Overall, 94.2% of the patients with small GISTs and 93.5% of those with gastric leiomyomas experienced some dyspepsia; however, total symptom scores were significantly lower in the GIST group than in the leiomyoma group (1.34 ± 1.27 vs 2.20 ± 1.70, P < 0.05). Each component of the symptom score demonstrated a statistically significant improvement in the GIST patients after ESD (P < 0.05), including epigastric pain (0.80 ± 0.90 vs 0.13 ± 0.46), heartburn (0.63 ± 1.08 vs 0.13 ± 0.41), regurgitation (0.55 ± 0.87 vs 0.22 ± 0.57), epigastric discomfort (0.70 ± 0.98 vs 0.32 ± 0.47), nausea and vomiting (0.27 ± 0.62 vs 0.05 ± 0.21), abdominal bloating (0.70 ± 0.90 vs 0.27 ± 0.49), and eructation (0.36 ± 0.61 vs 0.21 ± 0.46). For leiomyoma patients, symptoms such as heartburn, nausea, vomiting, and eructation improved after treatment; however, these improvements were not statistically significant (P > 0.05). Thus, the pathophysiology of dyspepsia symptoms may be different between the two groups.CONCLUSION: Symptoms of gastric small GISTs may mimic those of functional dyspepsia. An alternative diagnosis should be considered in patients with functional dyspepsia and treatment failure.     

Alterations in gut microbiota during remission and recurrence of diabetes after duodenal-jejunal bypass in rats

AIM: To observe the alterations in gut microbiota in high-fat diet(HFD)-induced diabetes recurrence after duodenal-jejunal bypass(DJB) in rats. METHODS: We assigned HDF- and low-dose streptozotocin-induced diabetic rats into two major groups to receive DJB and sham operation respectively. When the DJB was completed, we used HFD to induce diabetes recurrence. Then, we grouped the DJB-operated rats by blood glucose level into the DJB-remission(DJB-RM) group and the DJB-recurrence(DJB-RC) group. At a sequence of time points after operations, we compared calorie content in the food intake(calorie intake), oral glucose tolerance test, homeostasis model assessment of insulin resistance(HOMA-IR), concentrations of glucagon-like peptide 1(GLP-1), serum insulin, total bile acids(TBAs) and lipopolysaccharide(LPS) and alterations in colonic microbiota.RESULTS: The relative abundance of Firmicutes in the control(58.06% ± 11.12%; P 0.05 vs sham; P 0.05 vs DJB-RC) and DJB-RM(55.58% ± 6.16%; P 0.05 vs sham; P 0.05 vs DJB-RC) groups was higher than that in the sham(29.04% ± 1.36%) and DJB-RC(27.44% ± 2.17%) groups; but the relative abundance of Bacteroidetes was lower(control group: 33.46% ± 10.52%, P 0.05 vs sham 46.88% ± 2.34%, P 0.05 vs DJB-RC 47.41% ± 5.67%. DJB-RM group: 34.63% ± 3.37%, P 0.05 vs sham; P 0.05 vs DJB-RC). Escherichia coli was higher in the sham(15.72% ± 1.67%, P 0.05 vs control, P 0.05 vs DJB-RM) and DJB-RC(16.42% ± 3.00%; P 0.05 vs control; P 0.05 vs DJB-RM) groups than in the control(3.58% ± 3.67%) and DJB-RM(4.15% ± 2.76%) groups. Improved HOMA-IR(2.82 ± 0.73, P 0.05 vs DJB-RC 4.23 ± 0.72), increased TBAs(27803.17 ± 4673.42 ng/m L; P 0.05 vs DJB-RC 18744.00 ± 3047.26 ng/m L) and decreased LPS(0.12 ± 0.04 ng/m L, P 0.05 vs DJBRC 0.19 ± 0.03 ng/m L) were observed the in DJB-RM group; however, these improvements were reversed in the DJB-RC group, with the exception of GLP-1(DJB-RM vs DJB-RC P 0.05). CONCLUSION: Alterations in gut microbiota may be responsible for the diabetes remission and recurrence after DJB, possibly by influencing serum LPS and TBAs.     

Effects of electro-acupuncture on 5-HT,NOS and the gastric mucosa of stress rats

AIM: To study the effects of electro-acupuncture (EA) on 5-hydroxytryptophan (5-HT) levels, nitrous oxide (NOS) levels, nitric oxide (NO) levels, and the gastric mucosa in stress rats.METHODS: The changes of 5-HT and NOS were measured in the gastric mucosa, and NO and 5-HT were measured in the serum by biochemical methods. The gastric mucosa was examined pathohistologically in the stress rats with gastric mucosa damage after EA. The changes before and after stress by EA were compared.RESULTS: EA decreased the gastric mucosa damage index in the stress rats (2.71 ± 0.40 to 1.86 ± 0.69, P < 0.01). EA normalized NOS level in gastric mucosa to the control group. The changes before stress by EA was more obvious than that after stress. EA lowered the 5-HT levels in the gastric mucosa (μg/g wet weight, 6.91 ± 3.08 to 4.51 ± 1.62, P < 0.01). EA recovered the NO level in serum of the stress rats (μmol/L, 5.78 ± 1.49 to 7.91 ± 1.11, P < 0.05), and increased the levels of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in serum continuously.CONCLUSION: EA stimulation normalizes the NOS and NO levels in the gastric mucosa of stress rats. EA also lowers the high 5-HT levels and induces NO release.     

Decreased serum platelet derived growth factor BB levels in acute and increased in chronic pancreatitis

AIM: To examine circulating growth factor concentrations in patients with acute pancreatitis (AP) and chronic pancreatitis (CP), and walled-off pancreatic necrosis (WOPN).METHODS: Forty patients with mild AP, 40 patients with alcoholic CP, 33 patients with WOPN and 40 healthy subjects were examined. Serum concentrations of platelet derived growth factor BB (PDGF-BB), transforming growth factor β-1 (TGFβ-1), chemerin and high-mobility group box chromosomal protein 1 (HMBG1) were assayed by enzyme linked immunosorbent assay.RESULTS: Patients with mild AP and those with WOPN had significantly lower serum levels of PDGF-BB compared to healthy subjects (4.0 ± 0.61 ng/mL vs 6.2 ± 0.76 ng/mL, P = 0.027, and 1.60 ± 0.31 ng/mL vs 6.2 ± 0.76 ng/mL, P < 0.001, respectively), while CP was associated with higher serum levels of PDGF-BB (12 ± 1.3 ng/mL vs 6.2 ± 0.76 ng/mL, P < 0.001). Circulating TGFβ-1 and chemerin levels were elevated in CP patients (57 ± 3.6 ng/mL vs 39 ± 3.6 ng/mL, P < 0.001 and 73 ± 7.2 ng/mL vs 48 ± 2.3 ng/mL, P < 0.001, respectively), but not in patients with AP and WOPN. No significant changes in serum HMBG1 levels were found either in patients with AP, WOPN or CP.CONCLUSION: The serum levels of some growth factors and cytokines differ significantly in AP, WOPN and CP. These data suggest that selected growth factors and cytokines may be considered as potential diagnostic biomarkers in patients with pancreatic diseases.     

Effectiveness and safety of continuous wound infiltration for postoperative pain management after open gastrectomy

AIM: To prospectively evaluate the effectiveness and safety of continuous wound infiltration(CWI) for pain management after open gastrectomy. METHODS: Seventy-five adult patients with American Society of Anesthesiologists(ASA) Physical Status Classification System(ASA) grade 1-3 undergoing open gastrectomy were randomized to three groups. Group 1 patients received CWI with 0.3% ropivacaine(group CWI). Group 2 patients received 0.5 mg/m L morphine intravenously by a patient-controlled analgesia pump(PCIA)(group PCIA). Group 3 patients received epidural analgesia(EA) with 0.12% ropivacaine and 20 μg/m L morphine with an infusion at 6-8 m L/h for 48 h(group EA). A standard general anesthetic technique was used for all three groups. Rescue analgesia(2 mg bolus of morphine, intravenous) was given when the visual analogue scale(VAS) score was ≥ 4. The outcomes measured over 48 h after the operation were VAS scores both at rest and during mobilization, total morphine consumption, relative side effects, and basic vital signs. Further results including time to extubation, recovery of bowel function, surgical wound healing,mean length of hospitalization after surgery, and the patient's satisfaction were also recorded.RESULTS: All three groups had similar VAS scores during the first 48 h after surgery. Group CWI and group EA, compared with group PCIA, had lower morphine consumption(P 0.001), less postoperative nausea and vomiting(1.20 ± 0.41 vs 1.96 ± 0.67, 1.32 ± 0.56 vs 1.96 ± 0.67, respectively, P 0.001), earlier extubation(16.56 ± 5.24 min vs 19.76 ± 5.75 min, P 0.05, 15.48 ± 4.59 min vs 19.76 ± 5.75 min, P 0.01), and earlier recovery of bowel function(2.96 ± 1.17 d vs 3.60 ± 1.04 d, 2.80 ± 1.38 d vs 3.60 ± 1.04 d, respectively, P 0.05). The mean length of hospitalization after surgery was reduced in groups CWI(8.20 ± 2.58 d vs 10.08 ± 3.15 d, P 0.05) and EA(7.96 ± 2.30 d vs 10.08 ± 3.15 d, P 0.01) compared with group PCIA. All three groups had similar patient satisfaction and wound healing, but group PCIA was prone to higher sedation scores when compared with groups CWI and EA, especially during the first 12 h after surgery. Group EA had a lower mean arterial pressure within the first postoperative 12 h compared with the other two groups.CONCLUSION : CWI with ropivacaine yields a satisfactory analgesic effect within the first 48 h after open gastrectomy, with lower morphine consumption and accelerated recovery.     

Impact of clinical and procedural factors upon C reactive protein dynamics following transcatheter aortic valve implantation

AIM: To determine the effect of procedural and clinical factors upon C reactive protein(CRP) dynamics following transcatheter aortic valve implantation(TAVI).METHODS: Two hundred and eight consecutive patients that underwent transfemoral TAVI at two hospitals(Imperial, College Healthcare NHS Trust, Hammersmith Hospital, London, United Kingdom and San Raffaele Scientific Institute, Milan, Italy) were included. Daily venous plasma CRP levels were measured for up to 7 d following the procedure(or up to discharge). Procedural factors and 30-d safety outcomes according tothe Valve Academic Research Consortium 2 definition were collected. RESULTS: Following TAVI, CRP significantly increased reaching a peak on day 3 of 87.6 ± 5.5 mg/d L, P 0.001. Patients who developed clinical signs and symptoms of sepsis had significantly increased levels of CRP(P 0.001). The presence of diabetes mellitus was associated with a significantly higher peak CRP level at day 3(78.4 ± 3.2 vs 92.2 ± 4.4, P 0.001). There was no difference in peak CRP release following balloonexpandable or self-expandable TAVI implantation(94.8 ± 9.1 vs 81.9 ± 6.9, P = 0.34) or if post-dilatation was required(86.9 ± 6.3 vs 96.6 ± 5.3, P = 0.42), however, when pre-TAVI balloon aortic valvuloplasty was performed this resulted in a significant increase in the peak CRP(110.1 ± 8.9 vs 51.6 ± 3.7, P 0.001). The development of a major vascular complication did result in a significantly increased maximal CRP release(153.7 ± 11.9 vs 83.3 ± 7.4, P = 0.02) and there was a trend toward a higher peak CRP following major/lifethreatening bleeding(113.2 ± 9.3 vs 82.7 ± 7.5, P = 0.12) although this did not reach statistical significance. CRP was not found to be a predictor of 30-d mortality on univariate analysis. CONCLUSION: Careful attention should be paid to baseline clinical characteristics and procedural factors when interpreting CRP following TAVI to determine their future management.     

1H nuclear magnetic resonance spectroscopy-based metabonomic study in patients with cirrhosis and hepatic encephalopathy

AIM: To identify plasma metabolites used as biomarkers in order to distinguish cirrhotics from controls and encephalopathics.METHODS: A clinical study involving stable cirrhotic patients with and without overt hepatic encephalopathy was designed. A control group of healthy volunteers was used. Plasma from those patients was analysed using ¹H - nuclear magnetic resonance spectroscopy. We used the Carr Purcell Meiboom Gill sequence to process the sample spectra at ambient probe temperature. We used a gated secondary irradiation field for water signal suppression. Samples were calibrated and referenced using the sodium trimethyl silyl propionate peak at 0.00 ppm. For each sample 128 transients (FID’s) were acquired into 32 K complex data points over a spectral width of 6 KHz. 30 degree pulses were applied with an acquisition time of 4.0 s in order to achieve better resolution, followed by a recovery delay of 12 s, to allow for complete relaxation and recovery of the magnetisation. A metabolic profile was created for stable cirrhotic patients without signs of overt hepatic encephalopathy and encephalopathic patients as well as healthy controls. Stepwise discriminant analysis was then used and discriminant factors were created to differentiate between the three groups.RESULTS: Eighteen stabled cirrhotic patients, eighteen patients with overt hepatic encephalopathy and seventeen healthy volunteers were recruited. Patients with cirrhosis had significantly impaired ketone body metabolism, urea synthesis and gluconeogenesis. This was demonstrated by higher concentrations of acetoacetate (0.23 ± 0.02 vs 0.05 ± 0.00, P < 0.01), and b-hydroxybutarate (0.58 ± 0.14 vs 0.08 ± 0.00, P < 0.01), lower concentrations of glutamine (0.44 ± 0.08 vs 0.63 ± 0.03, P < 0.05), histidine (0.16 ± 0.01 vs 0.36 ± 0.04, P < 0.01) and arginine (0.08 ± 0.01 vs 0.14 ± 0.02, P < 0.03) and higher concentrations of glutamate (1.36 ± 0.25 vs 0.58 ± 0.04, P < 0.01), lactate (1.53 ± 0.11 vs 0.42 ± 0.05, P < 0.01), pyruvate (0.11 ± 0.02 vs 0.03 ± 0.00, P < 0.01) threonine (0.39 ± 0.02 vs 0.08 ± 0.01, P < 0.01) and aspartate (0.37 ± 0.03 vs 0.03 ± 0.01). A five metabolite signature by stepwise discriminant analysis could separate between controls and cirrhotic patients with an accuracy of 98%. In patients with encephalopathy we observed further derangement of ketone body metabolism, impaired production of glycerol and myoinositol, reversal of Fischer’s ratio and impaired glutamine production as demonstrated by lower b-hydroxybutyrate (0.58 ± 0.14 vs 0.16 ± 0.02, P < 0.0002), higher acetoacetate (0.23 ± 0.02 vs 0.41 ± 0.16, P < 0.05), leucine (0.33 ± 0.02 vs 0.49 ± 0.05, P < 0.005) and isoleucine (0.12 ± 0.02 vs 0.27 ± 0.02, P < 0.0004) and lower glutamine (0.44 ± 0.08 vs 0.36 ± 0.04, P < 0.013), glycerol (0.53 ± 0.03 vs 0.19 ± 0.02, P < 0.000) and myoinositol (0.36 ± 0.04 vs 0.18 ± 0.02, P < 0.010) concentrations. A four metabolite signature by stepwise discriminant analysis could separate between encephalopathic and cirrhotic patients with an accuracy of 87%.CONCLUSION: Patients with cirrhosis and patients with hepatic encephalopathy exhibit distinct metabolic abnormalities and the use of metabonomics can select biomarkers for these diseases.     

Esophageal Helicobacter pylori colonization aggravates esophageal injury caused by reflux

AIM: To investigate esophageal Helicobacter pylori (H. pylori) colonization on esophageal injury caused by reflux and the related mechanisms.METHODS: An esophagitis model, with acid and bile reflux, was surgically produced in male rats. The rats were randomly divided into either: (1) an esophagogastroduodenal anastomosis (EGDA) group; (2) an EGDA with H. pylori infection group; (3) a pseudo-operation with H. pylori infection group; or (4) a pseudo-operation group. All rats were kept for 36 wk. Based on the location of H. pylori colonization, the EGDA rats with H. pylori infection were subdivided into those with concomitant esophageal H. pylori colonization or those with only gastric H. pylori colonization. The esophageal injuries were evaluated grossly and microscopically. The expressions of CDX2 and MUC2 were determined by real-time polymerase chain reaction (RT-PCR) and immunohistochemistry. Ki-67 antigen expression was determined by immunohistochemistry. The mRNA levels of cyclin D1, c-Myc, Bax and Bcl-2 were determined by RT-PCR. Cell apoptosis was evaluated using the TdT-mediated dUTP nick-end labeling method.RESULTS: Esophagitis, Barrett’s esophagus (BE), and esophageal adenocarcinoma (EAC) developed in rats that underwent EGDA. When comparing rats with EGDA and concomitant esophageal H. pylori colonization to EGDA-only rats, the severity of injury (87.9 ± 5.2 vs 77.2 ± 8.6, macroscopically, 92.5 ± 8.0 vs 83.8 ± 5.5, microscopically, both P < 0.05) and the incidences of BE (80.0% vs 33.3%, P = 0.055) and EAC (60.0% vs 11.1%, P < 0.05) were increased. These increases were associated with upregulation of CDX2 and MUC2 mRNA (10.1 ± 5.4 vs 3.0 ± 2.9, 8.4 ± 4.6 vs 2.0 ± 3.2, respectively, Ps < 0.01) and protein (8.1 ± 2.3 vs 3.3 ± 3.1, 7.3 ± 4.0 vs 1.8 ± 2.7, respectively, all P < 0.05). The expression of Ki-67 (8.9 ± 0.7 vs 6.0 ± 1.7, P < 0.01) and the presence of apoptotic cells (8.3 ± 1.1 vs 5.3 ± 1.7, P < 0.01) were also increased significantly in rats with EGDA and concomitant esophageal H. pylori colonization compared with rats with EGDA only. The mRNA levels of cyclin D1 (5.8 ± 1.9 vs 3.4 ± 1.3, P < 0.01), c-Myc (6.4 ± 1.7 vs 3.7 ± 1.2, P < 0.01), and Bax (8.6 ± 1.6 vs 5.1 ± 1.3, P < 0.01) were significantly increased, whereas the mRNA level of Bcl-2 (0.6 ± 0.3 vs 0.8 ± 0.3, P < 0.01) was significantly reduced in rats with EGDA and concomitant esophageal H. pylori colonization compared with rats with EGDA only.CONCLUSION: Esophageal H. pylori colonization increases esophagitis severity, and facilitates the development of BE and EAC with the augmentation of cell proliferation and apoptosis in esophageal mucosa.     

Combination of symptoms,syndrome and disease: Treatment of refractory diabetic gastroparesis

AIM: To assess effect of combination of symptoms, syndrome and disease on treatment of diabetic gastroparesis with severe nausea and vomiting.METHODS: Professor Tong Xiaolin’s clinical electronic medical records of patients who were treated between January 1, 2006 and October 1, 2012 were used as a database. Patients who met the inclusion criteria were enrolled. General information (name, sex and age), symptoms and blood glucose levels were obtained from the clinic electronic medical record, which was supplemented by a telephone interview. The patient-rated Gastroparesis Cardinal Symptom Index (GCSI) was used to evaluate the severity of the symptoms of gastroparesis. The effects of the treatment were assessed by the change in the severity of the symptoms of gastroparesis and the change in blood glucose between the baseline levels and the post-treatment levels at 1, 2, 4, 8 and 12 wk.RESULTS: Forty-five patients had a mean GCSI nausea and vomiting severity score of 4.21 ± 0.67 and a total GCSI score of 2.77 ± 0.63 before treatment. There was a significant improvement in the nausea and vomiting score at every return visit compared with the baseline score (1 wk: 3.02 ± 1.04 vs 4.18 ± 0.71, P < 0.001; 2 wk: 2.32 ± 1.25 vs 4.16 ± 0.73, P < 0.001; 4 wk: 2.12 ± 1.26 vs 4.12 ± 0.73, P < 0.001; 8 wk: 1.79 ± 1.09 vs 4.24 ± 0.77, P < 0.001; 12 wk: 0.69 ± 0.92 vs 4.25 ± 0.70, P < 0.001). Twenty-five of the 45 patients had complete resolution of vomiting during the observation period (mean time to resolution was 37.9 ± 27.3 d). The postprandial fullness and early satiety subscale, bloating subscale and total GCSI scores were also improved. Finally, the blood glucose levels improved after treatment, although the change was not significant.CONCLUSION: Use of the combination of symptoms, syndrome and disease to treat diabetic gastroparesis with refractory nausea and vomiting may be a new treatment option.     

Protective role of hydrogen-rich water on aspirin-induced gastric mucosal damage in rats

AIM: To investigate the role of the hydrogen-rich water(HRW) in the prevention of aspirin-induced gastric mucosal injury in rats. METHODS: Forty male rats were allocated into four groups: normal control group, HRW group, aspirin group, and HRW plus aspirin group. The protective efficacy was tested by determining the gastric mucosal damage score. Malondialdehyde(MDA), superoxide dismutase(SOD), myeloperoxidase(MPO), interleukin(IL)-06 and tumor necrosis factor(TNF)-α in gastric tissues were evaluated. The serum levels of IL-1β and TNF-α were also detected. Histopathology of gastric tissues and localization of Cyclooxygenase 2(COX-2) were detected using hematoxylin and eosin staining and immunohistochemistry, respectively. RESULTS: Pretreatment with HRW obviously reduced aspirin-induced gastric damage scores(4.04 ± 0.492 vs 2.10 ± 0.437, P < 0.05). The oxidative stress levels of MDA and MPO in the gastric tissues increased significantly in the aspirin-treated group compared with the HRW group(2.43 ± 0.145 vs 1.79 ± 0.116 nmol/mg prot, P < 0.05 and 2.53 ± 0.238 vs 1.40 ± 0.208 U/g tissue, P < 0.05, respectively). HRW could obviously elevated the SOD levels in the gastric tissues(37.94 ± 8.44 vs 59.55 ± 9.02 nmol/mg prot, P < 0.05). Pretreatment with HRW significantly reduced IL-06 and TNF-α in the gastric tissues(46.65 ± 5.50 vs 32.15 ± 4.83 pg/mg, P < 0.05 and 1305.08 ± 101.23 vs 855.96 ± 93.22 pg/mg, P < 0.05), and IL-1β and TNF-α in the serum(505.38 ± 32.97 vs 343.37 ± 25.09 pg/mL, P < 0.05 and 264.53 ± 28.63 vs 114.96 ± 21.79 pg/mL, P < 0.05) compared to treatment with aspirin alone. HRW could significantly decrease the COX-2 expression in the gastric tissues(staining score: 8.4 ± 2.1 vs 2.9 ± 1.5, P < 0.05). CONCLUSION: HRW pretreatment alleviated the aspirin-induced gastric lesions by inhibiting the oxidative stress, inflammatory reaction and reducing the COX-2 in the gastric tissues.     

Role of moxibustion in inflammatory responses during treatment of rat ulcerative colitis

AIM: To investigate the efficacy of moxibustion in ulcerative colitis (UC) rats from morphological, immunological and molecular biological perspectives.METHODS: Thirty-two Sprague-Dawley rats were randomly assigned to a blank control group (normal rats, n = 6) and a model replication (MR) group (UC rats, n = 26). A UC model was established by 2,4,6-trinitrobenzenesulfonic acid/dextran sulfate sodium enema. Rats in the MR group were further randomly assigned to a 9-min moxibustion (9M) group (9 moxa-cone, n = 6), 6-min moxibustion (6M) group (6 moxa-cone, n = 6), 3-min moxibustion (3M) group (3 moxa-cone, n = 6), and a waiting list control (WLC) group (no moxibustion treatment, n = 6). Rats in the moxibustion treatment group were treated in 14 sessions over 28 d. Disease activity, local tissue morphology, serum level of interleukin (IL)-8 and IL-10, and expression of Toll-like receptor (TLR)9 as well as nuclear factor (NF)-κB p65 in colonic tissue were determined by disease activity index (DAI), hematoxylin and eosin staining, electron microscopy, enzyme-linked immunosorbent assay and Western blotting, respectively.RESULTS: DAI was lowest in the 9M group and highest in the WLC group. The differences in DAI between the moxibustion treatment (3M, 6M, 9M) and no treatment groups were significant for all one-to-one comparisons (0.60 ± 0.54 vs 1.20 ± 0.44, 0.60 ± 0.54 vs 1.80 ± 0.45, 0.60 ± 0.54 vs 3.0 ± 0.45, respectively, P < 0.05). Light and electron microscopy showed that the neatness of the glandular arrangement in colonic mucosal epithelia gradually increased in the WLC, 3M, 6M to 9M groups. IL-8 level successively decreased while IL-10 level increased from the WLC to 3M, 6M and 9M groups. The differences among these groups were significant for all comparisons (105.46 ± 8.75 vs 76.61 ± 3.58, 105.46 ± 8.75 vs 69.78 ± 1.87, 105.46 ± 8.75 vs 67.41 ± 1.84, respectively, P < 0.01 for IL-8; and 30.83 ± 1.29 vs 75.64 ± 1.90, 30.83 ± 1.29 vs 80.90 ± 3.16, 30.83 ± 1.29 vs 83.46 ± 2.37, respectively, P < 0.01 for IL-10), except comparison of 6M vs 9M. Expression of TLR9 and NF-κB p65 decreased in order: highest in the WLC group and lowest in the 9M group. In addition, the differences among the WLC, 3M, 6M and 9M groups were significant for all comparisons (0.492 ± 0.026 vs 0.380 ± 0.022, 0.492 ± 0.026 vs 0.355 ± 0.005, 0.492 ± 0.026 vs 0.327 ± 0.015, respectively, P < 0.05 for TLR9; and 0.436 ± 0.041 vs 0.326 ± 0.022, 0.436 ± 0.041 vs 0.293 ± 0.006, 0.436 ± 0.041 vs 0.265 ± 0.017, respectively, P < 0.05 for NF-κB p65).CONCLUSION: Moxibustion repairs damaged colonic mucosa, suppresses serum IL-8, activates serum IL-10 level, and decreases expression of TLR-9 and NF-κB p65 in UC rats.     

Higher level of heme oxygenase-1 in patients with stroke than TIA

Background

There is a reverse relationship between serum bilirubin level and incidence of stroke, heme oxygenase-1 (HO-1) can catalyze heme into bilirubin, it is unknown the association of HO-1 level with risk of stroke.

Methods

Sixty patients with stroke and fifty patients with transient ischemic attack (TIA) were recruited. Serum level of HO-1, total and direct bilirubin, alanine transaminase, live function, lipid profile and infection status of patients were measured.

Results

Significant differences were found between two groups in terms of serum levels of HO-1 (163.6±58.7 vs. 141.2±49.7, P=0.032), total bilirubin (10.1±4.6 vs. 15.8±2.7, P<0.001), direct bilirubin (3.2±2.1 vs. 5.9±1.2, P<0.001), fasting glucose (6.7±3.1 vs. 4.9±1.3, P<0.001), cholesterol (4.4±1.1 vs. 3.9±0.8, P=0.005) and diastolic blood pressure (DBP) (84.9±9.4 vs. 81.3±9.2, P=0.046). In multivariate analysis, serum direct bilirubin (OR, 2.83; P<0.001), total bilirubin (OR, 1.82, P=0.001), DBP (OR, 0.88, P=0.041), and fasting glucose (OR, 0.34, P<0.001) were independent predictors of stroke.

Conclusions

Serum HO-1 level is higher in patients with stroke than TIA, but the bilirubin level is lower in patients with stroke than TIA and is an independent predictor of stroke. Further studies are warranted to clarify the underlying link among HO-1, bilirubin and stroke.