Phospholipase A2 enzymes PLA2G2A and PLA2G12B as potential diagnostic and prognostic biomarkers in cholangiocarcinoma.

BACKGROUND: Phospholipase A2 (PLA2) enzymes are pivotal in various biological processes, such as lipid mediator production, membrane remodeling, bioenergetics, and maintaining the body surface barrier. Notably, these enzymes play a significant role in the development of diverse tumors. AIM: To systematically and comprehensively explore the expression of the PLA2 family genes and their potential implications in cholangiocarcinoma (CCA). METHODS: We conducted an analysis of five CCA datasets from The Cancer Genome Atlas and the Gene Expression Omnibus. The study identified differentially expressed genes between tumor tissues and adjacent normal tissues, with a focus on PLA2G2A and PLA2G12B. Gene Set Enrichment Analysis was utilized to pinpoint associated pathways. Moreover, relevant hub genes and microRNAs for PLA2G2A and PLA2G12B were predicted, and their correlation with the prognosis of CCA was evaluated. RESULTS: PLA2G2A and PLA2G12B were discerned as differentially expressed in CCA, manifesting significant variations in expression levels in urine and serum between CCA patients and healthy individuals. Elevated expression of PLA2G2A was correlated with poorer overall survival in CCA patients. Additionally, the study delineated pathways and miRNAs associated with these genes. CONCLUSION: Our findings suggest that PLA2G2A and PLA2G12B may serve as novel potential diagnostic and prognostic markers for CCA. The increased levels of these genes in biological fluids could be employed as non-invasive markers for CCA, and their expression levels are indicative of prognosis, underscoring their potential utility in clinical settings.

Positive effects of brisk walking and Tai Chi on cognitive function in older adults: An fNIRS study.

Exercise has shown to have beneficial effects on cognition in older adults. The purpose of this study was to investigate the cortical hemodynamic responses during the word-color Stroop test (WCST) prior and after acute walking and Tai Chi exercise by functional near-infrared spectroscopy (fNIRS). Twenty participants (9 males, mean age 62.8 ± 5.2), first underwent a baseline WCST test, after which they took three WCST tests in a randomized order, (a) after sitting rest (control), (b) after 6 minutes performing Tai Chi Quan, and (c) after a bout of 6 minutes brisk walking. During these four WCST tests cortical hemodynamic changes in the prefrontal area were monitored with fNIRS. Both brisk walking and Tai Chi enhanced hemodynamic activity during the Stroop incongruent tasks, leading to improved cognitive performance (quicker reaction time). Brisk walking induced a greater hemodynamic activity in the right dorsolateral prefrontal cortex (DLPFC) and ventrolateral prefrontal cortex (VLPFC) area, whereas Tai Chi induced a greater bilateral hemodynamic activity in the DLPFC and VLPFC areas. The present study provided empirical evidence of enhanced hemodynamic response in task- specific regions of the brain that can be achieved by a mere six minutes of brisk walking or Tai Chi in older adults.

Prefrontal cortical hemodynamics and functional network organization during Tai Chi standing meditation: an fNIRS study.

Introduction: Tai Chi standing meditation (Zhan Zhuang, also called pile standing) is characterized by meditation, deep breathing, and mental focus based on theories of traditional Chinese medicine. The purpose of the present study was to explore prefrontal cortical hemodynamics and the functional network organization associated with Tai Chi standing meditation by using functional near-infrared spectroscopy (fNIRS). Methods: Twenty-four channel fNIRS signals were recorded from 24 male Tai Chi Quan practitioners (54.71 ± 8.04 years) while standing at rest and standing during Tai Chi meditation. The general linear model and the SPM method were used to analyze the fNIRS signals. Pearson correlation was calculated to determine the functional connectivity between the prefrontal cortical sub-regions. The small world properties of the FC networks were then further analyzed based on graph theory. Results: During Tai Chi standing meditation, significantly higher concentrations of oxygenated hemoglobin were observed in bilateral dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC), frontal eye field (FEF), and pre-motor cortex (PMC) compared with the values measured during standing rest (p < 0.05). Simultaneously, significant decreases in deoxygenated hemoglobin concentration were observed in left VLPFC, right PMC and DLPFC during Tai Chi standing meditation than during standing rest (p < 0.05). Functional connectivity between the left and right PFC was also significantly stronger during the Tai Chi standing meditation (p < 0.05). The functional brain networks exhibited small-world architecture, and more network hubs located in DLPFC and VLPFC were identified during Tai Chi standing meditation than during standing rest. Discussion: These findings suggest that Tai Chi standing meditation introduces significant changes in the cortical blood flow and the brain functional network organization.

Mechanism and therapeutic strategy of hepatic TM6SF2-deficient non-alcoholic fatty liver diseases via in vivo and in vitro experiments.

BACKGROUND: The lack of effective pharmacotherapies for nonalcoholic fatty liver disease (NAFLD) is mainly attributed to insufficient research on its pathogenesis. The pathogenesis of TM6SF2-efficient NAFLD remains unclear, resulting in a lack of therapeutic strategies for TM6SF2-deficient patients. AIM: To investigate the role of TM6SF2 in fatty acid metabolism in the context of fatty liver and propose possible therapeutic strategies for NAFLD caused by TM6SF2 deficiency. METHODS: Liver samples collected from both NAFLD mouse models and human participants (80 cases) were used to evaluate the expression of TM6SF2 by using western blotting, immunohistochemistry, and quantitative polymerase chain reaction. RNA-seq data retrieved from the Gene Expression Omnibus database were used to confirm the over-expression of TM6SF2. Knockdown and overexpression of TM6SF2 were performed to clarify the mechanistic basis of hepatic lipid accumulation in NAFLD. MK-4074 administration was used as a therapeutic intervention to evaluate its effect on NAFLD caused by TM6SF2 deficiency. RESULTS: Hepatic TM6SF2 levels were elevated in patients with NAFLD and NAFLD mouse models. TM6SF2 overexpression can reduce hepatic lipid accumulation, suggesting a protective role for TM6SF2 in a high-fat diet (HFD). Downregulation of TM6SF2, simulating the TM6SF2 E167K mutation condition, increases intracellular lipid deposition due to dysregulated fatty acid metabolism and is characterized by enhanced fatty acid uptake and synthesis, accompanied by impaired fatty acid oxidation. Owing to the potential effect of TM6SF2 deficiency on lipid metabolism, the application of an acetyl-CoA carboxylase inhibitor (MK-4074) could reverse the NAFLD phenotypes caused by TM6SF2 deficiency. CONCLUSION: TM6SF2 plays a protective role in the HFD condition; its deficiency enhanced hepatic lipid accumulation through dysregulated fatty acid metabolism, and MK-4074 treatment could alleviate the NAFLD phenotypes caused by TM6SF2 deficiency.

[Distribution Characteristics of Disinfection By-Products and the Effects of Booster Chlorination in Long-Distance Water Supply Systems].

It is difficult for waterworks that add chlorine into finished water once to maintain sufficient residual chlorine at unfavorable points of the pipe network that supply water for large areas of coverage. Therefore, booster chlorination was employed for a long-distance water distribution system. The study was performed in H City with a water supply system serving about 400 km2 of downtown and rural areas. The purpose of this work is to obtain the distribution characteristics of disinfection by-products (DBPs) in the booster chlorination disinfection pipe network through uniformly distributed sampling analysis. The results showed that detected DBPs include trichloromethane (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM) and tribromomethane (TBM), dichloroacetic acid (DCAA), trichloroacetic acid (TCAA), dichloroacetonitrile (DCAN), bromochloroacetonitrile (BCAN), and trichloronitromethane (TCNM). The concentrations of the regulated DBPs were found to be lower than the standard limits specified in the Sanitary Standard for Drinking Water (GB5749-2006). Before booster chlorination, the average concentrations of the DBPs mentioned (expressed as mean±deviation) were (8.08±3.34), (9.77±2.91), (7.38±4.82), (2.65±2.02), (2.95±3.26), (6.02±6.06), (3.13±2.48), (1.61±2.05), and (0.15±0.10) µg·L-1, while afterwards, they were increased to (10.30±4.55), (11.73±3.60), (8.23±5.22), (2.95±2.45), (3.29±3.60), (8.15±7.58), (3.31±2.61), (1.33±2.04), and (0.12±0.06) µg·L-1, respectively. Trihalomethanes (THMs) and haloacetic acids (HAAs) increased by 6.32%-26.60% and 5.32%-42.71%, respectively, after booster chlorination. In addition, raw water quality and seasonal changes had a certain impact on the occurrence of DBPs. The levels of DBPs in summer were generally higher than those in spring or autumn. According to the analysis of DBP formation potential of source water, finished water, and tap water, it was found that the risk of DBPs exceeding the standard limit may exist in the water supply system of H City; therefore, further optimization of the treatment process should be considered to ensure water quality.

[Occurrence and Prediction Model of Disinfection By-Products in Tap Water].

Disinfection by-products (DBPs) are defined as important parameters that can deteriorate drinking water quality. The investigation was performed at a laboratory located on a campus in H City of the Zhejiang province. The purpose of the work was to obtain knowledge on the occurrence of DBPs in tap water and boiled water taken from the same pipe, to establish a statistical model to predict DBPs information in tap water based on physicochemical parameters, and to evaluate carcinogenic and non-carcinogenic risks caused by DBPs on a predictional level. The results showed three categories of trihalomethanes (THMs), haloacetonnitrile (HANs), and haloacetic acids (HAAs), including 10 species of disinfection by-products detected in drinking water. The detection rate of target DBPs in tap water was 100% and the concentrations varied in the ranges of 10.12-28.39, 0.98-5.19, and 2.65-7.83 µg·L-1, respectively. In boiled water, bromochloracetonitrile (BCAN) was not detected; the detection rates of tribromomethane(TBM), trichloroacetonitrile (TCAN), and dibromoacetonitrile (DBAN) were 46.43%, 82.14%, and 92.86%, respectively, while the detection rate for other DBPs was 100%. The concentrations of THMs, HANs, and HAAs were in the ranges of 0.60-12.58, 0.02-0.52, and 2.42-5.86 µg·L-1, respectively. After heating, the concentrations of THMs and HANs decreased by 84.22% and 91.45%, respectively. No obvious decrease was found for HAAs. The pH value and specific ultraviolet absorbance (SUVA) had positive correlation with DBPs, whereas residual chlorine and ammonia nitrogen had negative correlation with DBPs. Based on the correlation between the physicochemical parameters and DBPs, a multiple linear regression prediction model of THMs was established, with deviation less than 10.00%, which can be used for the prediction of THMs in tap water. Based on the EPA recommended health risk assessment model, the carcinogenic and non-carcinogenic risks of chlorine disinfection by-products through oral intake were calculated. It was found that the carcinogenic risks caused by the disinfection by-products in the tap and boiled water were (17.24-84.63)×10-6 and (25.49-258.82)×10-7, respectively, and the non-carcinogenic risks were (4.17-50.32)×10-2 and (6.52-107.74)×10-3, respectively. The carcinogenic risk caused mainly by THMs and bromodicloromethane (BDCM) contributed the highest cancer risk in tap water, while for boiled water, trichloromethane (TCM) was found to contribute the highest cancer and non-carcinogenic risk. In boiled water, the reduction of THMs was up to 94.38%, and the cancer risk was reduced by 79.00%.

Dopamine D2 Receptor-Mediated Modulation of Rat Retinal Ganglion Cell Excitability.

Ganglion cells (RGCs) are the sole output neurons of the retinal circuity. Here, we investigated whether and how dopamine D2 receptors modulate the excitability of dissociated rat RGCs. Application of the selective D2 receptor agonist quinpirole inhibited outward K+ currents, which were mainly mediated by glybenclamide- and 4-aminopyridine-sensitive channels, but not the tetraethylammonium-sensitive channel. In addition, quinpirole selectively enhanced Nav1.6 voltage-gated Na+ currents. The intracellular cAMP/protein kinase A, Ca2+/calmodulin-dependent protein kinase II, and mitogen-activated protein kinase/extracellular signal-regulated kinase signaling pathways were responsible for the effects of quinpirole on K+ and Na+ currents, while phospholipase C/protein kinase C signaling was not involved. Under current-clamp conditions, the number of action potentials evoked by positive current injection was increased by quinpirole. Our results suggest that D2 receptor activation increases RGC excitability by suppressing outward K+ currents and enhancing Nav1.6 currents, which may affect retinal visual information processing.

[Disinfection By-products and the Relevant Health Risk in the Water Supply System in H City of Zhejiang Province].

The occurrence of 18 types of disinfection by-products (DBPs) in two waterworks and the corresponding water supply networks of H City in Zhejiang Province was determined by gas chromatography coupled with electron capture detector (GC-ECD). The correlation between DBPs and organic precursors, and health risks caused by DBPs, were discussed. Results showed that the disinfection by-products detected in drinking water in H City mainly include trihalomethanes (THMs), haloacetic acid (HAAs), haloacetonitrile (HANs) and trichloronitromethane (HNMs), with highest concentrations of THMs followed by HAAs. In the finish water of CX Waterworks and tap water supplied by CX Water works, concentrations of THMs ranged from 7.70 to 32.73µg·L-1and 9.00 to 51.42µg·L-1, respectively, and those of HAAs 3.05 to 21.30µg·L-1 and 6.00 to 26.79µg·L-1, respectively. The THMs in finished water and tap water of TH Waterworks were in the range 8.65-38.76µg·L-1 and 12.09-42.04µg·L-1, respectively, and those of HAAs were 2.42-14.79µg·L-1 and 2.80-33.40µg·L-1, respectively. The DBPs in the finished and tap water of the two waterworks were at lower levels than the limitations regulated by the Sanitary Standard for Drinking Water (GB 5749-2006). The index of dissolved organic carbon (DOC) and UV254 were adopted to describe the organic compounds, and it was found that trichloromethane (TCM) was significantly negatively correlated with DOC and UV254in tap water. Based on the EPA recommended health risk assessment model, the carcinogenic and non-carcinogenic risks of chlorine disinfection by-products in the oral intake route were calculated. It was found that the carcinogenic risks caused by the disinfection by-products in the finished water and tap water of H City were 5.94×10-6-4.76×10-5 and 5.94×10-6-5.56×10-5, respectively, while the non-carcinogenic risks were 0.91×10-2-4.20×10-2 and 1.26×10-2-4.72×10-2, respectively. The carcinogenic risk is mainly from THMs:bromodichloromethane (BDCM) contributes the highest cancer risk, and the non-carcinogenic risk is mainly from TCM.

Jaundice caused by protrusion of a hepatic cyst into common bile duct that was resolved by choledochoscopic needle-knife electrotomy: a case report.

BACKGROUD: Hepatic cysts are the most frequent, innocuous, space-occupying lesions of the liver. The majority of solitary liver cysts are nonsymptomatic. When liver cysts reach a large size, there are some complications, including infection, rupture, spontaneous hemorrhage, obstructive jaundice, and neoplastic degeneration. Percutaneous aspiration, fenestration, hepatic resection, and liver transplantation have been proposed for symptomatic patients. CASE PRESENTATION: In this case report, we describe a 41-year-old woman who presented with persistent liver dysfunction, indolent xanthochromia, and skin itching for 3 months. After a series of tests, she has a 5.0 × 5.3 cm hepatic cyst with many separations in the left medial liver lobe. The obstructive jaundice was caused by a large pedunculated lump protruding into the common bile duct from the left hepatic duct. She was treated with laparotomy and this lump was completely removed from the root by choledochoscopic needle-knife electrotomy with a good clinical response. Postoperative pathology of the lump suggested a hepatic cyst wall without heterocysts or tumor cells. CONCLUSION: Hepatic cyst wall protruding into the common bile duct can form capsular lump and result in indolent jaundice. Choledochoscopic high-frequency needle-knife electrotomy could be considered as a simple, safe and effective complementary approach for benign mass on the bile duct wall.

Long Noncoding RNA NEAT1 Promotes Growth and Metastasis of Cholangiocarcinoma Cells.

Long noncoding RNAs (lncRNAs) are known to play important roles in cancers. However, little is known about lncRNAs in cholangiocarcinoma (CCA), a cholangiocyte malignancy with poor prognosis. We investigated the role of nuclear paraspeckle assembly transcript 1 (NEAT1) lncRNA in promoting CCA. qRT-PCR analysis of patient samples showed that NEAT1 expression was higher in CCA tumors than in matched adjacent nontumor tissue. NEAT1 levels were also higher in CCA cell lines than in a normal biliary epithelium cell line (HIBEpic). NEAT1 knockdown in CCA cell lines using shNEAT1 reduced cell proliferation and colony formation in CCK-8 and colony formation assays, respectively. CCA cells transfected with shNEAT1 also exhibited reduced metastasis and invasiveness in Transwell assays. NEAT1 knockdown cells produced smaller tumors, demonstrating that NEAT1 promotes tumor growth in vivo. Silencing of NEAT1 increased E-cadherin expression in vitro, and E-cadherin expression was inversely correlated with NEAT1 expression in CCA tissue samples. RIP and ChIP assays suggest that NEAT1 is recruited to the E-cadherin promoter by EZH2 (enhancer of zeste homolog 2), where it represses E-cadherin expression. These findings indicate that NEAT1 exerts oncogenic effects in CCA. We postulate that NEAT1 is a potentially useful diagnostic and therapeutic target for CCA.

Endoscopic Sphincterotomy for Gallbladder Muddy Stones or Sludge in Patients With Papillary Disease: A Retrospective Study.

BACKGROUND: The formation of gallbladder stones is associated with dysfunctional contraction and duodenal papilla diseases. However, endoscopic sphincterotomy can improve the contraction of the gallbladder and resolve duodenal papilla disease. AIM: The aim of the study was to assess the feasibility and effectiveness of endoscopic sphincterotomy in the treatment of muddy stones or sludge in the gallbladder during papillary disease. METHODS: The clinical data of 53 patients with gallbladder muddy stones or sludge undergoing endoscopic sphincterotomy were retrospectively analyzed. RESULTS: A total of 53 patients received successful endoscopic sphincterotomy with no serious complications. Sphincterotomy did not significantly lower resting gallbladder volume from 63.2±10.8 to 50.1±5.9 mL (P>0.05), but significantly increased gallbladder ejection fraction from 0.41±0.13 to 0.63±0.16 (P<0.01), as measured by the lipoid food test. The static liver and gallbladder imaging examination also showed an increase in gallbladder ejection fraction from 0.45±0.08 to 0.68±0.11 (P<0.01). In addition, the choledochus pressure reduced from 21.9±4.0 to 15.6±2.5 mm Hg, and the gallbladder muddy stones or sludge disappeared after endoscopic sphincterotomy. At the end of the follow-up period, there was no relapse of sludge or muddy stones in the gallbladder. CONCLUSIONS: The formation of gallbladder muddy stones or sludge is associated with papilla disease. Endoscopic sphincterotomy can resolve papilla disease, decrease gallbladder bile stasis, improve gallbladder evacuation, and prevent the formation of gallbladder stones.

The modified pancreatic stent system for prevention of post-ERCP pancreatitis: a case-control study.

BACKGROUND: Prophylactic pancreatic stents after endoscopic retrograde cholangiopancreatography (ERCP) can help prevent post-ERCP pancreatitis. However most of the pancreatic stents need to be removed by another ERCP. The aim of this observational study was to investigate the feasibility and effectiveness of the modified pancreatic stent system for prevention of post-ERCP pancreatitis. METHODS: From November 2013 to November 2015, a total of 230 patients who had prophylactic pancreatic stent placed for prevention of post-ERCP pancreatitis at a single institution were identified and stratified. In this case-control design, 150 patients received an ordinary pancreatic stent, and 80 patients received the modified pancreatic stent. The main outcome measures were the difficulty level and complications of pancreatic stent placement and extraction between the two groups. RESULTS: In ordinary group, the average time of pancreatic stent and nasal biliary drainage placement was 3.5 ± 0.6 min. There were 13 cases of stent proximal migration (8.7%), 20 cases of stent spontaneous abscission (13.3%), 5 cases of acute pancreatitis (3.3%) (2 cases for stent abscission) and 7 cases of hyperamylasemia (4.7%) after ERCP. One hundred thirty patients received extra duodenoscope (86.7%) to remove the stent, and 4 cases had acute pancreatitis and 5 patients had hyperamylasemia after removing the proximal migratory stents. In modified group, the average time of pancreatic stent system placement was 4.9 ± 0.7 min, but there was only one case of stent abscission (1.3%), 2 cases of acute pancreatitis (2.5%) and 3 cases of hyperamylasemia (3.8%). The new pancreatic stents were removed directly under x-ray without complication. CONCLUSIONS: The modified pancreatic stent system has the same effect of preventing post-ERCP pancreatitis, lower rate of stents proximal migration and spontaneous abscission, and the advantage of easier removed compared with ordinary pancreatic stent.

Choledochoscopic high-frequency needle-knife electrotomy for treatment of anastomotic strictures after Roux-en-Y hepaticojejunostomy.

BACKGROUND: Anastomotic stricture is a complex and substantial complication following Roux-en-Y hepaticojejunostomy. Initially, endoscopic and percutaneous approaches are often attempted, but the gold standard remains surgical biliary reconstruction, especially for refractory stricture. However, this solution leaves much room for improvement, due to the challenging nature of the biliary reconstruction procedure, in which anastomotic stricture may still occur. AIMS: To investigate the feasibility and effectiveness of choledochoscopic high-frequency needle-knife electrotomy as an intervention in the treatment of anastomotic strictures following Roux-en-Y hepaticojejunostomy. METHODS: From February 2010 to October 2014, clinical data was collected and retrospectively compared for patients who underwent balloon dilation or/and choledochoscopic high-frequency needle-knife electrotomy for the treatment of anastomotic strictures after Roux-en-Y hepaticojejunostomy. RESULTS: A total of 38 patients underwent successful choledochoscopic treatment and all the anastomotic strictures were removed successfully, 19 of which were treated with electrotomy, 7 with balloon dilation, and 12 with both electrotomy and balloon dilation. Among these groups,the average operating times were 6.9 ± 2.4 min,10.1 ± 6.8 min, and 20.2 ± 13.5 min, respectively. The average stent supporting times were 6.3 ± 0.7 months, 6.5 ± 0.6 months, and 6.1 ± 0.4 respectively. The mean follow-up after stent removal was 42.1 ± 27.4 months, and in 26.3 % (5/19), 28.5 % (2/7) and 16.7 % (2/12) of cases, recurrent anastomotic stricture occurred. Of these 9 total patients with recurrent anastomotic, two patients were successfully rescued by full-covered self-expanding removable metal stents and 7 patients by electrotomy combined with balloon dilation. CONCLUSIONS: Choledochoscopic high-frequency needle-knife electrotomy is both feasible and safe in the treatment of anastomotic stricture after Roux-en-Y hepaticojejunostomy, with a similar long-term outcome to balloon dilation in treating anastomotic stricture after Roux-en-Y hepaticojejunostomy. A combination of choledochoscopic electrotomy concurrent with balloon dilation should be recommended based on the low rate of recurrence.

Common bile duct injury by fibrin glue: report of a rare complication.

Fibrin glue is widely used in clinical practice and plays an important role in reducing postoperative complications. We report a case of a 65-year-old man, whose common bile duct was injured by fibrin glue, with a history of failed laparoscopic cholecystectomy and open operation for uncontrolled laparoscopic bleeding. In view of the persistent liver dysfunction, xanthochromia and skin itching, the patient was admitted to us for further management. Ultrasound, computed tomography, and magnetic resonance cholangiopancreatography (MRCP) revealed multiple stones in the common bile duct, and liver function tests confirmed the presence of obstructive jaundice and liver damage. Endoscopic retrograde cholangiopancreatography was unsuccessfully performed to remove choledocholithiasis, but a small amount of tissue was removed and pathologically confirmed as calcified biliary mucosa. This was followed by open surgery for suspicious cholangiocarcinoma. There was no evidence of cholangiocarcinoma, but the common bile duct wall had a defect of 8 mm × 10 mm at Calot's triangle. A hard, grid-like foreign body was removed, which proved to be solid fibrin glue. Subsequently, the residual choledocholithiasis was removed by a choledochoscopic procedure, and the common bile duct deletion was repaired by liver round ligament with T-tube drainage. Six months later, endoscopy was performed through the T-tube fistula and showed a well-repaired bile duct wall. Eight months later, MRCP confirmed no bile duct stenosis. A review of reported cases showed that fibrin glue is widely used in surgery, but it can also cause organ damage. Its mechanism may be related to discharge reactions.

Choledochoscopic high-frequency needle-knife electrotomy as an effective treatment for intrahepatic biliary strictures.

BACKGROUND AND AIM: Hepatolithiasis is associated with the presence of intrahepatic biliary strictures, and balloon dilatation is the main approach. However, this method is difficult to implement if the bile duct distal to the stricture is blocked by stones. Therefore, alternative methods need to be explored to effectively treat hepatolithiasis. The aim of this study is to investigate the feasibility and effectiveness of choledochoscopic high-frequency needle-knife electrotomy for the treatment of intrahepatic biliary strictures. METHODS: Clinical data of 58 patients suffering from intrahepatic bile duct strictures from January 2011 to January 2013 were retrospectively analyzed. Choledochoscopic electrotomy was used to resolve the strictures. RESULTS: One hundred thirty-four sites of intrahepatic bile duct strictures were discovered. The average operating time of electrotomy is 5.6 min (range, 1 ∼ 15 min). Structured bile duct tissue bleeding occurred in eight sites (8/134, 6.0%) but were resolved by endoscopic high-frequency electric cautery. After the operations, 14 cases of cholangitis (14/58, 24.1%), three cases of delayed hemobilia, one case of liver abscess (1/58, 1.7%), and seven cases of stenting exodus (7/58, 12.1%) were observed despite conservative treatment and stenting reset. The average supporting time was 7.0 months (6 ∼ 9 months). No abnormal bile duct structure or presence of stone was found according to choledochoscopy. The follow-up period ranged from 12 to 48 months. Hepatolithiasis recurred in five (5/58, 8.6%) patients, and the cumulative recurrent probability of intrahepatic bile duct stricture was 5.2% (7/134). CONCLUSIONS: Choledochoscopic high-frequency needle-knife electrotomy could be considered as a simple, safe, and effective complementary approach for treating intrahepatic biliary strictures.

Biliary casts after liver transplantation: morphology and biochemical analysis.

AIM: To investigate the pathogenesis of biliary casts after liver transplantation relative to their morphology and biochemical markers. METHODS: The microstructure of biliary casts was assessed using scanning electron microscopy and Hematoxylin and eosin staining assessed their histology. The expression levels of CD3, CD5, CD34, CD68 and CD79a in these biliary casts were evaluated immunohistochemically. RESULTS: Biliary casts differed widely in their microstructure, with some containing blood vessels positive for CD34 and collagen fibers with positive Masson staining. Large numbers of neutrophils and other inflammatory cells were present, but only on the edge of the biliary casts; although the boundaries were clear without crossover. None of the biliary casts contained T-lymphocytes, B-lymphocytes, macrophages and other inflammatory cells. CONCLUSION: The microcostructure of biliary casts differed. Bacteria and acute rejection are not clearly related to their formation.

Clinical analysis and significance of cholangiography for biliary cast/stone after orthotopic liver transplantation.

Cholangiography is an important method for the diagnosis of biliary complications after orthotopic liver transplantation. The cholangiography after orthotopic liver transplantation presents special challenges, especially in patients with biliary cast/stone and biliary stenosis. We described the T-tube cholangiography combined therapeutic fibro-choledochoscopy for the diagnosis and treatment of biliary cast following after orthotopic liver transplantation. Fourteen patients who developed biliary cast/stone after liver transplantation were analyzed retrospectively. The complications were divided into three temporal stages, early, medium, and late. Hepatic functions and the characteristics of the bile duct were observed by T-tube cholangiography and endoscopy. The biliary cast after liver transplantation was divided into three categories: Solitary, multiple, and columnar. Three months after liver transplantation, bile ducts appeared fuzzy by T-tube cholangiography, but no evidence of biliary cast was found. The bile duct was feculent with flocculation during the middle stage 3-6 months after liver transplantation. At six months after transplantation, bile ducts (especially intrahepatic bile ducts) were distended; cholangiectasis was obvious with biliary cast. The intrahepatic bile duct stricture was observed on occasion by T-tube cholangiography and the intrahepatic bile duct could be thin and distended, and resembled withered branches or strings of beads. The intrahepatic bile ducts even disappeared at this stage; hepatic functions were usually unacceptable and the icterus gradually aggravated. Four cases were diagnosed earlier according to the categories of stone and stage. Curative therapy was performed promptly and the clinical outcome was acceptable. Biliary tracts of the transplanted livers could be observed by T-tube channels and biliary complications were treated effectively by therapeutic fibro-choledochoscopy. It is necessary to combine T-tube cholangiography with fibro-choledochoscopy for the diagnosis and treatment of biliary complications after orthotopic liver transplantation.

[Correlation of E-cadherin hypermethylation to tumorigenesis and development of gastric cancer].

BACKGROUND & OBJECTIVE: CpG island hypermethylation in promoter region of E-cadherin (E-cad) gene plays an important role in tumorigenesis of many tumors. This study was to explore the correlation of E-cadherin hypermethylation to tumorigenesis and development of gastric cancer. METHODS: Methylation-specific polymerase chain reaction (MSP) was used to detect the methylation of E-cad gene in 41 specimens of gastric cancer, 40 specimens of premalignant gastric lesions and 38 specimens of normal gastric tissues. The expression of E-cad protein was detected by SP immunohistochemistry. RESULTS: The positive rate of E-cad gene methylation was significantly higher in gastric cancer than in premalignant lesions and normal tissues (19.5% vs. 2.5% and 0.0%, P<0.05). The positive rate of E-cad protein was significantly lower in gastric cancer tissues than in premalignant lesions and normal tissues (70.7% vs. 97.5% and 100.0%, P<0.05). The positive rate of E-cad gene methylation was significantly higher in poorly differentiated cancer tissues than in well differentiated cancer tissues (43.8% vs. 4.0%, P<0.05), significantly higher in gastric cancer tissues with lymph node metastasis than in those without lymph node metastasis (33.3% vs. 5.0%, P<0.05), and significantly higher in gastric cancer tissues with serosa invasion than in those without serosa invasion (35.0% vs. 4.8%, P<0.05). The positive rate of E-cad protein was significantly lower in gastric cancer tissues with E-cad gene methylation than in those without E-cad gene methylation (0.0% vs. 87.9%, P<0.05). CONCLUSION: CpG island hypermethylation of E-cad gene exists in gastric cancer, which down-regulates E-cad expression and might be involved in tumorigenesis and development of gastric cancer.

[A study of interleukin-10 gene polymorphism in irritable bowel syndrome].

OBJECTIVE: To investigate whether three diallelic polymorphisms at the position -1082, -819 and -592 in the promoter region of the IL-10 gene were associated with diarrhea-predominant irritable bowel syndrome (D-IBS). METHODS: The IL-10 gene -1082, -819 and -592 position polymorphisms were genotyped by amplification refractory mutation systems-polymerase chain reaction (ARMS-PCR) methods in 43 patients with D-IBS and 41 healthy subjects (HS). RESULTS: Compared with HS, D-IBS patients had a greater frequency of T/T genotype at IL-10 gene promoter -819 position (67.4% vs 39.0%, P < 0.05), the frequencies of -819 C/T and C/C genotype were not significantly different (23.3% vs 43.9% and 9.3% vs 17.1%, P > 0.05). D-IBS patients also had a greater frequency of -592 A/A genotype compared with HS (67.4% vs 39.0%, P < 0.05), the frequencies of -592 C/A and C/C genotype were not significantly different (23.3% vs 43.9% and 9.3% vs 17.1%, P > 0.05). No significant difference was found in genotype at IL-10 gene promoter -1082 position. The -819 T allele frequency in D-IBS was significantly higher than that in control (79.1% vs 61.0%, P < 0.05), whereas -819 C allele frequency in D-IBS was lower (20.9% vs 39.0%, P < 0.05). D-IBS patients also had a greater frequency of -592 A allele compared with HS (79.1% vs 61.0%, P < 0.05), -592 C allele frequency in D-IBS was lower (20.9% vs 39.0%, P < 0.05). No significant difference was found in -1082 G or A allele frequency. CONCLUSIONS: The presence of -819 T/T and -592 A/A genotype may be related to development of D-IBS.

[The prevention of hepatolithiasis and biliary stricture post choledochojejunostomy].

OBJECTIVE: To investigate the prevention of hepatolithiasis and biliary stricture post choledochojejunostomy using choledochoscopy technique and evaluate feasibility and efficacy of choledochojejunostomy and artificial valve of efferent loop in preventing reflux. METHODS: To analyze the data of 47 patients with hepatolithiasis who had been operated with Roux-en-Y cholangiojejunostomy and artificial valve of efferent loop to prevent bilio-intestinal regurgitation. Of the patients, 19 were marked with silver nip at the jejunum export of bilio-intestinal anastomosis. The regurgitation, recurrence, anastomotic stricture and their managements after the surgery were investigated. RESULTS: The bilio-intestinal regurgitation were found in 32 cases (32/47, 68.1%), it suggested that artificial valve could not prevent bilio-intestinal regurgitation efficiently. Two cases of hepatolithiasis recurred and were cured by sinus tract placement with the aid of silver nip mark under choledochoscope instead of re-operation. Of the 6 cases with anastomotic stricture, 5 cases were treated successfully with stone extraction, biliary stent dilatation under the percutaneous transhepatic cholangioscopy (PTCS) and the other one case died. CONCLUSIONS: Silver nip mark provides safe and simple path for the cholangioscopy, it made the treatment of the recurrent biliary stricture and stone safe and brief, made the cholangioscopy play more important role in the hepatolithiasis, residual stone and biliary stricture. PTCS is mini-invasive, safe, simple and effective.