[Role of p38 mitogen-activated protein kinase pathway in pathogenesis of ulcerative colitis].

OBJECTIVE: To elucidate the role of p38 mitogen-activated protein kinase (p38MAPK) in the pathogenesis of ulcerative colitis (UC) and DSS-induced colitis in mice. METHODS: (1) 27 Balb/c mice were divided randomly into three groups: DSS-induced colitis group, normal control group and SB203580 treatment group. In DSS-induced colitis group, mice were feed with 5% DSS solution. In SB203580 treatment group, mice were feed with 5%DSS solution for 72 hours, then treated with intraperitoneal injection of SB203580 (1 mg/kg) once daily. Disease activity index (DAI) was record to evaluate the severity of colitis. The mice were executed after 7 days. The levels of TNF-alpha and IL-1beta were measured by ELISA. (2) A total of 54 cases were included in the study. 36 cases were patients with active ulcerative colitis, 18 cases were normal mucosa from 18 colon cancer cases served as control. Effects of SB203580 (a selective p38MAPK inhibitor) on expression of TNF-alpha and IL-1beta in intestinal mucosal biopsy specimens from patients with ulcerative colitis were determined on condition of tissue culture. RESULTS: (1) The DAI scores, the levels of TNF-alpha and IL-1beta in SB203580 group were lower significantly compared with DSS group (P < 0.05), and were increased significantly compared with normal control group (P < 0.05). (2) The levels of TNF-alpha and IL-1beta in intestinal mucosal biopsy specimens in SB203580 treatment group were lower significantly than those in UC group (P < 0.05). CONCLUSION: SB203580 can inhibit p38MAPK signal transduction pathway, then reduce the expression of pro-inflammatory cytokine TNF-alpha and IL-1beta.

Glial-derived neurotrophic factor regulates intestinal epithelial barrier function and inflammation and is therapeutic for murine colitis.

Although enteric glial cells (EGCs) have been demonstrated to play a key role in maintaining intestinal epithelial barrier integrity, it is not known how EGCs regulate this integrity. We therefore hypothesized that glial-derived neurotrophic factor (GDNF) produced by EGCs might be involved in this regulation. Here we investigated the role of GDNF in regulating epithelial barrier function in vivo. Recombinant adenoviral vectors encoding GDNF (Ad-GDNF) were administered intracolonically in experimental colitis induced by dextran sulphate sodium (DSS). The disease activity index (DAI) and histological score were measured. Epithelial permeability was assayed using Evans blue dye. The anti-apoptotic potency of GDNF in vivo was evaluated. The expression of tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and myeloperoxidase (MPO) activity were measured by ELISA assay and/or RT-PCR. The expression of ZO-1, Akt, caspase-3, and NF-kappaB p65 was analysed by western blot assay. Our results showed that GDNF resulted in a significant reduction in enhanced permeability, inhibited MPO activity, IL-1beta and TNF-alpha expression, and increased ZO-1 and Akt expression. Moreover, GDNF strongly prevented apoptosis in vivo and significantly ameliorated experimental colitis. Our findings indicate that GDNF participates directly in restoring epithelial barrier function in vivo via reduction of increased epithelial permeability and inhibition of mucosal inflammatory response, and is efficacious in DSS-induced colitis. These findings support the notion that EGCs are able to regulate intestinal epithelial barrier integrity indirectly via their release of GDNF in vivo. GDNF is namely an important mediator of the cross-talk between EGCs and mucosal epithelial cells. GDNF may be a useful therapeutic approach to the treatment of inflammatory bowel disease.

Laparoscopic versus open transhiatal approach for adenocarcinoma of the esophagogastric junction: A systematic review and meta-analysis.

BACKGROUND: The incidence of adenocarcinoma of the esophagogastric junction (AEG) is increasing worldwide. Laparoscopic transhiatal approach (LTH) has gained growing popularity in the treatment of AEG. However, its safety and efficacy need to be evaluated. METHODS: Original studies comparing LTH with open transhiatal approach (OTH) were searched. Meta-analysis was performed using RevMan 5.3. RESULTS: Nine studies involving 2149 patients were eligible. Compared with OTH, LTH was associated with longer operation time (mean difference [MD] = 31min, 95%CI [20,41], P < 0.001) while less blood loss (MD = -103ml [-135, -72], P < 0.001), and harvested similar number of lymph nodes (MD = 0.1 [-1.2, 1.4], P = 0.89). There were no differences in time to ambulation (MD = -0.79 days [-1.77, 0.20], P = 0.12) or time to first flatus (MD = -0.82 days [-1.76, 0.11], P = 0.08); however, LTH was associated with shorter postoperative hospital stay (MD = -1.70 days [-2.34, -1.05], P < 0.001). The mortality after surgery was comparable for LTH and OTH (risk difference [RD] = -0.00 [-0.01, 0.01], P = 0.55). The incidence of total major complications was similar in LTH (6.1%) and OTH (8.4%) (RD = -0.02 [-0.05, 0.01], P = 0.12); there were no significant differences in the incidence of each complication. Furthermore, LTH achieved similar 2-year overall survival (OS) rate (risk ratio [RR] = 1.17 [0.86, 1.60], P = 0.31) while higher 5-year OS rate (RR = 1.43 [1.18, 1.73], P = 0.0003) and significant improvement of OS (univariable hazard ratio = 0.65 [0.50, 0.84], P = 0.0009; multivariable hazard ratio = 0.59 [0.44, 0.80], P = 0.0006). CONCLUSIONS: LTH is feasible and safe for AEG, and may provide more favorable short-term outcomes and potential long-term survival benefit, which needs to be confirmed by randomized trials.

Gastrectomy with omentum preservation versus gastrectomy with omentectomy for locally advanced gastric cancer: A systematic review and meta-analysis.

BACKGROUND: Omentectomy has been traditionally a part of standard radical gastrectomy. Its clinical benefit for locally advanced gastric cancer (LAGC) remains controversial. This study aimed at evaluating the impact of gastrectomy with omentum preservation (GOP) on survival, recurrence, surgical outcomes and postoperative complications by comparing with gastrectomy with omentum resection (GOR). METHODS: Original studies comparing GOP with GOR in LAGC were searched. Meta-analysis was performed using RevMan 5.4. RESULTS: Seven studies involving 1879 patients were analyzed. Compared with GOR, GOP achieved significantly better overall survival (HR = 0.75 [0.60, 0.95], P = 0.01), with similar relapse-free survival (HR = 0.84 [0.68, 1.03], P = 0.10). The two groups had similar total recurrence rate (OR = 0.86 [0.68, 1.08], P = 0.19) and no significant differences in rates of peritoneal, hematogenous, locoregional or distant lymph node recurrences. GOP had significantly less blood loss (MD = -83 [-139, -28] ml, P = 0.003) and tended to have shorter operation time (MD = -28 [-58, 2] min, P = 0.06), with similar harvested number of lymph nodes (MD = -0.4 [-2.6, 1.8], P = 0.70). The incidences of total all grade and major complications were similar in GOP and GOR (all grade: 31.8% vs. 30.3%, OR = 1.08 [0.79, 1.46], P = 0.64; major: 9.2% vs. 10.1%, OR = 1.14 [0.55, 2.34], P = 0.73). There were no significant differences in incidences of complication or postoperative mortality. CONCLUSIONS: Omentum preservation did not affect curability or survival in LAGC. These findings require validation in randomized controlled trials with large sample sizes.

Amelioration of dextran sulfate sodium-induced colitis by neuropeptide Y antisense oligodeoxynucleotide.

BACKGROUND: Neuropeptide Y (NPY) from enteric neurons has been shown to play an important role in immune and inflammatory responses. The purpose of the present study was to investigate the effects of NPY antisense oligodeoxynucleotides (ODNs) on an experimental model of ulcerative colitis (UC). METHODS: NPY antisense ODNs were administered in experimental colitis induced by dextran sulfate sodium (DSS). The disease activity index (DAI) and histological score were observed. The tumor necrosis factor (TNF)-alpha and NPY levels were measured by enzyme-linked immunosorbent assay. Phosphorylated Akt (p-Akt) expression was determined by immunohistochemical staining. Activated nuclear factor (NF)-kappaB was assessed by western blot analysis. Myeloperoxidase (MPO) activity was determined by using MPO assay kit. RESULTS: A significant improvement was observed in DAI and histological score in rats with NPY antisense ODNs, and the increase in NPY and TNF-alpha levels, MPO activity, and the expression p-Akt and p-NF-kappaB in rats with DSS-induced colitis was significantly reduced following the administration of NPY antisense ODNs. CONCLUSION: The administration of NPY antisense ODNs leads to an amelioration of DSS-induced colitis, suggesting that NPY plays an important role in modulating inflammation in colitis, and NPY antisense ODNs may be a useful therapeutic approach to the treatment of UC.

[Protective effects of emodin on intestinal lesion in rat model with acute necrotizing pancreatitis].

OBJECTIVE: To explore the protective effects and mechanism of Emodin on intestinal lesion in the rats with acute necrotizing pancreatitis (ANP). METHODS: Thirty SD rats were randomly divided into 3 groups: sham-operated (SO) group, ANP group and Emodin-treated group. ANP was induced by retro-pumping 3.5% sodium cholate to pancreaticobiliary duct. 5.5 hours after modeling, phenol red, which was employed to measure intestinal transit, was injected to duodenum. 0.5 hour later, rats were sacrificed to collect intestine for the results of intestinal transit and other tests of intestine. Furthermore, intestinal tissue (HE staining) was observed by light microscope, and the activity of nuclear factor-kappa B (NF-kappaB) in intestine was detected by immunohistochemical method. The content of intestinal tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) was detected with the method of enzyme-labeled immunosorbent assay (ELISA). RESULTS: Compared with SO group, there was significantly decrease of intestinal transit in ANG group (P < 0.05). Furthermore, intestinal transit in Emodin-treated group significantly increased when compared with ANP group (P < 0.05). NF-kappaB p65 positive rate of intestinal cell nuclei, content of intestinal TNF-alpha and IL-1beta in ANP group were obviously higher than those in SO group (P < 0.05). After the treatment of Emodin, NF-kappaB p65 positive rate of intestinal cell nuclei, content of TNF-alpha and IL-1beta were decreased (P < 0.05). Moreover, there was a negative correlation between intestinal transit and content of TNF-alpha, IL-1beta, with correlation coefficients--0.83, -0.76, respectively (P < 0.05). CONCLUSION: Emodin could increase intestinal transit, suppress the activity of NF-kappaB in intestine, decrease the content of intestinal TNF-alpha and IL-1beta, and attenuate the pathological damage of intestine.

Incidence of lymph node metastasis at each station in Siewert types â ¡/â ¢ adenocarcinoma of the esophagogastric junction: A systematic review and meta-analysis.

The optimal extent of lymphadenectomy for adenocarcinoma of the esophagogastric junction (AEG) has been continuously debatable. The study aimed to determine the incidence of lymph node metastasis at each station in Siewert types Ⅱ/Ⅲ AEG. PubMed was searched and publications reporting metastasis at each nodal station were eligible. Meta-analysis was performed using RevMan 5.3. Twenty-one studies involving 4662 patients were included. The incidence of lymph node metastasis was high (≥20%) in stations No. 3, 1, 2 and 7 in decreasing order, and moderate (10-20%) in stations No. 9, 19 and 110. The incidence did not exceed 10% in stations No. 10, 11p, 20, 8a, 4sa, 4 s b and 4d, was less than 5% in stations No. 5, 6, 11d, 12a, and even close to 0 in stations No. 107, 111 and 112. Compared with type Ⅲ tumors, type Ⅱ tumors had significantly lower incidence in some abdominal stations including No. 3, 4sa, 4 s b, 6, 8a and 10, while significantly higher in the lower mediastinal stations. The present analysis established a map of lymph node metastasis in Siewert types Ⅱ/Ⅲ AEG, which may serve as a valuable reference for the extent of lymphadenectomy.

Glial-derived neurotrophic factor regulates enteric mast cells and ameliorates dextran sulfate sodium-induced experimental colitis.

BACKGROUND & AIMS: Although interactions between enteric glial cells (EGCs) and enteric mast cells have been demonstrated to play an important role in the pathogenesis of inflammatory bowel disease (IBD), the exact mechanisms by which EGCs regulate enteric mast cells are still unknown. The aims of this study were to investigate whether glial-derived neurotrophic factor (GDNF), which has been confirmed to be produced mostly by EGCs, might regulate enteric mast cells and ameliorate dextran sulfate sodium (DSS)-induced experimental colitis. METHODS: Recombinant adenoviral vectors encoding GDNF (Ad-GDNF) were administered intracolonically in experimental colitis induced by DSS. The disease activity index and histological score were measured. The expression of tumour necrosis factor-α (TNF-α), interleukin-6 and myeloperoxidase (MPO) activity were measured by ELISA assay. The expression of trypsin and ß-hexosaminidase were evaluated. GDNF specific receptor (GFR-α1/RET) was detected. The calcium reflux was tested by microplate reader. The expression p-JNK was analyzed by western blot assay. RESULTS: GDNF resulted in a significant inhibition of the activation of enteric mast cells by down-regulating JNK signal pathway, lessening intracellular calcium influx, and then reducing the degranulation as well as the expression of pro-inflammatory cytokines via combing with its receptor (GFR-α1/RET) in mast cells, and these inhibitory effects were abrogated by treatment with neutralizing antibody against GDNF. Moreover, the administration of GDNF led to an amelioration of experimental colitis. CONCLUSIONS: GDNF are able to regulate enteric mast cells and ameliorate experimental colitis. GDNF might be an important mediator of the cross-talk between EGCs and enteric mast cells, and GDNF might be a useful therapeutic drug for IBD.

[Influence of integrated traditional Chinese and Western medicine therapy on serum resistin levels in patients with severe acute pancreatitis: a randomized controlled trial].

BACKGROUND: Resistin level is high in patients with severe acute pancreatitis (SAP), and resistin is expected to be a new marker for evaluating the severity of acute pancreatitis. OBJECTIVE: To explore the influence of integrated traditional Chinese and Western medicine therapy on serum resistin levels in SAP patients. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: Twenty-eight SAP patients meeting inclusion criteria from Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University were included, and the patients were randomly divided into treatment group and placebo group. There were 13 patients in the treatment group and 15 patients in the placebo group. Patients in the treatment group were given traditional Chinese herbal medicine in addition to the conventional treatment. Patients in the placebo group were given placebo in addition to the conventional treatment. MAIN OUTCOME MEASURES: The serum resistin levels on admission, and days 1, 3, 5, and 7 after the admission were detected. RESULTS: The serum resistin levels on admission in all the patients were higher than normal level, and there was no significant difference between the two groups (P>0.05). On days 1, 3, 5, and 7 after admission, the resistin levels in the treatment group were (3.29 + or - 1.66) microg/L, (3.71 + or - 1.05) microg/L, (3.08 + or - 1.47) microg/L and (3.62 + or - 1.67) microg/L, and in the control group (5.16 + or - 1.93) microg/L, (5.07 + or - 1.53) microg/L, (4.88 + or - 1.47) microg/L and (5.12 + or - 1.48) microg/L, respectively. The resistin levels were lower in the treatment group than in the control group (P<0.05). CONCLUSION: Serum resistin level in SAP patients can be decreased by integrated traditional Chinese medicine and Western medicine therapy.

[Risk factors and infection characteristics of secondary pancreatic infection in severe acute pancreatitis].

OBJECTIVE: To explore risk factors and infection characteristics of secondary pancreatic infection in severe acute pancreatitis (SAP). METHODS: A clinical data of 49 patients with secondary pancreatic infection in severe acute pancreatitis (SPI group)were matched with 49 patients without infection in severe acute pancreatitis (NSPI group) between January 2003 and December 2005. The two groups were analyzed by a case-control study. Conditional Logistic regression model univariate and multivariate were used to screen out risk factors. The types of infection, the peak infection and the bacteria spectrum were analyzed in SPI group. RESULTS: (1) In univariate Logistic regression analysis, 7 factors including continuous hypoalbuminemia, prolonged time of central venous catheter, usage of hormone, high APACHE II scores, multi-antibiotics, intestine dysfunction and continuous hyperglycemia were selected out. Moreover, the first three were statistically significant in multivariate Logistic regression analysis. (2) Pancreatic abscess ranked first in SPI group. Of all the pancreatic infection, 22.5% occurred within two weeks and 71.4% occurred in the 4th week or later. (3) In SPI group, 81 strains of microorganisms were cultured, including 45 strains of gram-negative bacteria (55.6%), 22 strains of gram-positive bacteria (27.2%), and 14 strains of fungi (17.3%). The common gram-negative bacteria were Escherichia coli, and the common gram-positive bacteria were Staphylococci and Enterococci. The fungi included Monilia and Yeastoid fungus. Further study revealed that 35 strains of all the microorganisms were intestinal bacteria (43.2%). CONCLUSIONS: Continuous hypoalbuminemia, prolonged time of central venous catheter and usage of hormone were independent risk factors of SPI. The main type of infection was pancreatic abscess. Gram-negative bacteria, were the common bacteria causing secondary pancreatic infection.

[Risk factor analysis of severe acute pancreatitis complicated by pancreatic encephalopathy].

OBJECTIVE: To study the risk factors for severe acute pancreatitis (SAP) complicated by pancreatic encephalopathy (PE). METHODS: Clinical data from 255 patients with SAP from January 2005 to December 2006 were reviewed. Thirty-one SAP patients had PE, and 224 SAP patients did not. Clinical characteristics of SAP patients in both PE group and non-PE group were analyzed. RESULTS: Ranson scale and the incidence rates of acute respiratory distress syndrome (ARDS), renal failure, hypoproteinemia, hypocalcemia and hyperglycosemia in PE group were higher than those in non-PE group (P<0.05). There were no significant differences in acute physiology and chronic health evaluation II and CT severity index scales, the activities of amylase and lipase, the incidence rate of liver function failure, the infection rate and the operability between the PE group and the non-PE group (P>0.05). Multivariate logistic regression analysis showed that ARDS and hyperglycosemia were high risk factors. Cure rate in PE group was higher than that in non-PE group. CONCLUSION: Nosogenesis of PE is the result of multiple factors. ARDS and hyperglycosemia may be the high risk factors for PE.

[Effects of Chaiqin Chengqi Decoction on activation of nuclear factor-kappaB in pancreas of rats with acute necrotizing pancreatitis].

OBJECTIVE: To explore the mechanism of Chaiqin Chengqi Decoction (CQCQD) in treatment of rats with acute necrotizing pancreatitis (ANP). METHODS: Thirty SD rats were randomly divided into 3 groups: sham-operated (SO) group, ANP group and CQCQD-treated group. ANP was induced by retro-pumping 3.5% sodium cholate to common bile duct. Blood sample was collected from abdominal vein for examination and the pancreatic tissue samples were taken for making pathology section 6 hours later. The pancreatic tissue (HE staining) was observed by light microscope. The content of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) was detected with the method of enzyme-linked immunosorbent assay, and the activation of nuclear factor-kappaB (NF-kappaB) in pancreas was detected by immunohistochemical method. RESULTS: Compared with the SO group, there was dramatic increase in the white blood cell (WBC) counts and AMY level in the ANP group (P<0.05, P<0.01). Compared with the ANP group, the WBC counts and AMY level in CQCQD-treated group were significantly reduced (P<0.05). The edema, inflammatory infiltration, haemorrhage and necrosis scores and total pathological score in the ANP group were obviously higher than those in the SO group (P<0.01). The edema, haemorrhage and inflammatory infiltration scores and the total pathological score in CQCQD-treated group were decreased (P<0.05). The integral optical density of NF-kappaB p65 positive cells of pancreas in CQCQD-treated group was lower than that in the ANP group (P<0.05). CONCLUSION: CQCQD can reduce the content of serum TNF-alpha and IL-6, depress the activation of NF-kappaB, and lessen the pancreatic lesions.

Can S-1 replace fluorouracil for advanced gastric cancer? A PRISMA-compliant systematic review and meta-analysis.

It remains to be seen whether S-1 can be a replacement for infusional fluorouracil (5-FU) for advanced gastric cancer (AGC). The aim of this study was to compare the efficacy and safety of S-1 with 5-FU in AGC.PubMed and Cochrane Library were searched. Randomized controlled trials and meta-analyses comparing S-1 with 5-FU for AGC were eligible. Meta-analysis was performed using RevMan 5.2.Seven trials involving 2443 patients were included. Compared with 5-FU, S-1 showed no significant prolongation of overall survival (OS) (hazard ratio [HR] = 0.91, 95% confidence interval [CI] [0.83-1.01], P = 0.07) and progression-free survival (HR = 0.89, 95% CI [0.70-1.13], P = 0.35), but longer time to treatment failure (HR = 0.74, 95% CI [0.56-0.97], P = 0.03). The objective response rates were comparable (risk ratio [RR] = 1.36, 95% CI [0.95, 1.96], P = 0.10). Regarding treatment-related deaths and hematological toxicities, there was significant heterogeneity between Asian and non-Asian trials, and subgroup analysis was applied. In Asian patients, there was a significant increase in hematological toxicities such as leukopenia (grade 1-4: RR = 1.22, 95% CI [1.08, 1.37], P = 0.001; grade 3-4: RR = 2.21, 95% CI [1.52, 3.21], P < 0.0001), neutropenia (grade 1-4: RR = 1.29, 95% CI [1.11, 1.48], P = 0.0005; grade 3-4: RR = 1.87, 95% CI [1.11, 3.17], P = 0.02), and thrombocytopenia (grade 1-4: RR = 1.71, 95% CI [1.22, 2.41], P = 0.002) in S-1-containing regimens compared with 5-FU-containing regimens, but without significant difference in treatment-related mortality rate (risk difference [RD] = 0.00, 95% CI [-0.01, 0.01], P = 0.68). In non-Asian patients, S-1-containing regimens were, however, associated with significantly fewer treatment-related deaths (RD = -0.02, 95% CI [-0.05, -0.00], P = 0.04), as well as less all grade 1-4 and grade 3-4 hematological toxicities except anemia. There was no significant heterogeneity in nonhematologic toxicities between Asian and non-Asian trials. Lower incidence of grade 1-4 nausea, diarrhea, mucositis, grade 3-4 mucositis, increased creatinine, and decreased calculated creatinine clearance was observed in S-1-containing regimens.S-1 could not improve OS, but increase some hematological toxicities in Asian patients. Therefore, special attention on hematological toxicities should be paid to Asian patients because S-1 is administered on an outpatient basis.

Effect of PLCε gene silencing on inhibiting the cancerous transformation of ulcerative colitis.

The aim of the present study was to investigate the effect of phosphoinositide-specific phospholipase Cε (PLCε) gene silencing on the inhibition of cancer development in ulcerative colitis (UC) and to explore the pathogenesis and carcinogenic mechanism of UC, in order to facilitate the establishment of novel strategies for the treatment of UC, prevent the cancerous transformation of UC and discern the association between inflammation and cancer. A pGenesil-PLCε RNA interference vector was constructed and transfected into HEK293 cells (pGenesil-PLCε group). HEK293 cells transfected with pGenesil empty plasmid were set as the negative control (pGenesil-NC group). The expression of PLCε was observed, and molecules associated with the PLC signaling pathway were detected using a reverse transcription-quantitative polymerase chain reaction and western blotting. ELISA was used to determine the expression of serum interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) of mice in which the PLCε gene had been silenced. Compared with the pGenesil-NC group, the mRNA and protein levels of PLCε were significantly decreased in the pGenesil-PLCε group. In addition, the mRNA levels of K-ras, NF-κB, Fas and Bcl-2 were markedly reduced, while P53 mRNA level was notably enhanced, in the pGenesil-PLCε group, and these changes were accompanied by similar changes in the corresponding protein levels. The serum IL-1 and TNF-α expression in the PLCε gene-silenced mice was significantly reduced compared with that in the control mice. In conclusion, PLCε RNA silencing can effectively inhibit the cancerous transformation of UC by regulating the colorectal cancer-related cell proliferation and cell cycle in vivo. In addition, PLCε RNA silencing can suppress the expression of inflammatory factors in vitro.

Laparoscopic splenectomy with or without devascularization of the stomach for liver cirrhosis and portal hypertension: a systematic review.

BACKGROUND: Open splenectomy and devascularization are effective treatments for cirrhotic patients with severe thrombocytopenia and variceal bleeding. However, it remains controversial whether laparoscopic splenectomy (LS) and devascularization (LSD) can be indicated and beneficial in these patients. OBJECTIVES: A systematic review of the efficacy and safety of LS and LSD for patients with liver cirrhosis and portal hypertension was undertaken to clarify controversy about their utilization in such patients. METHODS: A systematic search strategy was performed to retrieve relevant studies from PubMed and Embase.com. The literature search and data extraction were independently performed by two reviewers. RESULTS: Sixteen articles met the inclusion criteria. The methodology of the identified articles was poor. Six hundred and fifty-one patients, including 478 LS patients and 173 LSD patients, were involved in efficacy and safety evaluations. There was wide variability in the outcome measures between studies. There was only one death in the patients underwent LSD. Reported major complications included post-operative bleeding requiring re-surgery, pancreatic leakage and gastric perforation. Seven studies were identified with comparisons between laparoscopic and open procedures. No meta-analysis was possible because of heterogeneity between studies and lack of randomization. CONCLUSIONS: The publications reviewed revealed LS and LSD to be safe and effective in the setting of liver cirrhosis and portal hypertension. From the comparison articles, laparoscopic procedures appear to be superior to open procedures regarding blood loss, hospital stay, complication rate and liver function impairment. However, it is difficult to draw firm statistical conclusions due to lack of high-quality evidence.

Tetrandrine suppresses amyloid-ß-induced inflammatory cytokines by inhibiting NF-κB pathway in murine BV2 microglial cells.

Microglial cells play an important role in mediating neuroinflammation in Alzheimer's disease (AD) by production of a series of proinflammatory mediators and clearance of Aß peptides and senile plaques. Tetrandrine, a bisbenzylisoquinoline alkaloid isolated from the Chinese herb Radix Stephania tetrandra, has been demonstrated to decrease the expression of proinflammatory mediators by inhibition of NF-κB activation. Here we investigated whether tetrandrine may affect the phagocytosis of microglia and the expression of cytokines and NF-κB in murine BV2 microglial cells. We found that fibrillar Amyloid-ß (fAß) induced phagocytosis of microglia and dramatically increased the levels of interleukin 1 beta (IL-1ß) and tumor necrosis factor alpha (TNF-α) as well as the expression of phospho NF-κB p65 in microglia cultures. The treatment with tetrandrine resulted in downregulation of phospho NF-κB p65 expression and strikingly reduced the production of IL-1ß and TNF-α. However, tetrandrine did not affect fAß induced phagocytosis of microglia. In conclusion, tetrandrine can decrease microglial detriment of neurotoxicity while maintaining microglial benefit of neuroprotection. Tetrandrine may be an efficacious and promising remedy in the treatment of AD.

Tetrandrine attenuates spatial memory impairment and hippocampal neuroinflammation via inhibiting NF-κB activation in a rat model of Alzheimer's disease induced by amyloid-ß(1-42).

BACKGROUND: The neuroinflammation characterized by glial activation and release of proinflammatory mediators is considered to play a critical role in the pathogenesis of Alzheimer's disease (AD). Tetrandrine, a bisbenzylisoquinoline alkaloid isolated from the Chinese herb radix Stephania tetrandra, has been demonstrated to decrease the expression of proinflammatory mediators by inhibition of nuclear factor-κB (NF-κB) activation. The purpose of the study was to investigate effects of tetrandrine on experimental model of AD. MATERIALS AND METHODS: Tetrandrine was administered in a rat model of AD induced by amyloid-ß (Aß)(1-42). The learning and memory impairment was examined using Morris water maze; the extent of histological injury in hippocampus was determined by Nissl staining; NF-κB DNA binding activity was assessed by electrophoretic mobility shift assay; the expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1ß was measured by enzyme-linked immunosorbent assay. RESULTS: A significant improvement was observed in learning and memory impairment in rats with tetrandrine, and the increase in NF-κB DNA binding activity, the over-expression in IL-1ß and TNF-α as well as the increased histological injury in hippocampus in rats induced by Aß(1-42) were significantly reduced following administration of tetrandrine. CONCLUSION: Tetrandrine could significantly ameliorate Aß(1-42)-induced spatial learning and memory impairment, and the beneficial effect of tetrandrine treatment could be linked, at least in part, to the inhibition of NF-κB activity and the downregulation of expression of IL-1ß and TNF-α, suggesting that administration of tetrandrine may provide a therapeutic approach for AD.