Gut microbiota therapy for nonalcoholic fatty liver disease: Evidence from randomized clinical trials.

Nonalcoholic fatty liver disease (NAFLD) has a high prevalence worldwide, but there are no medications approved for treatment. Gut microbiota would be a novel and promising therapeutic target based on the concept of the gut-liver axis in liver disease. We reviewed randomized controlled trials on gut microbiota therapy in NAFLD in this study to evaluate its efficacy and plausibility in NAFLD.

New anti-reflux plastic stent to reduce the risk of stent-related cholangitis in the treatment of biliary strictures.

BACKGROUND: There is little data available on the role of new anti-reflux plastic stents (ARPSs). AIM: To compare the use of ARPSs with that of traditional plastic stents (TPSs) for patients with biliary strictures. METHODS: Consecutive patients with biliary strictures who underwent first endoscopic biliary stenting between February 2016 and May 2019 were included. The onset of stent-related cholangitis, stent patency, clinical success, and other adverse events were evaluated. RESULTS: Sixty-seven patients in the ARPS group and 66 patients in the TPS group were included in the final analyses. Fewer patients experienced stent-related cholangitis in the ARPS group than that in the TPS group (8 patients vs 18 patients; P = 0.030). The median time till the onset of first stent-related cholangitis was later in the ARPS group than that in the TPS group (128.5 d vs 76 d; P = 0.039). The cumulative median stent patency in the ARPS group was 185 d, which was significantly longer than that in the TPS group (133 d; P = 0.001). The clinical success rates and other adverse events did not significantly differ between both groups. CONCLUSION: Placement of new ARPS might be a safe and effective optional therapeutic strategy to reduce the risk of stent-related cholangitis and prolong stent patency.

Peroral endoscopic myotomy for management of gastrointestinal motility disorder.

Achalasia is a type of esophageal motility disorder, consisting of relaxation dysfunction of the lower esophagus and disturbed esophageal peristalsis. Related clinical symptoms include dysphagia, regurgitation, chest pain, and weight loss. Traditional treatment options include endoscopic botulinum toxin injection, endoscopic pneumatic dilation, and laparoscopic Heller's myotomy. These therapies mainly relieve symptoms by reducing the pressure on the lower esophageal sphincter and reducing blood flow resistance at the esophagogastric junction. Based on endoscopic submucosal dissection and natural orifice transluminal endoscopic surgery, peroral endoscopic myotomy (POEM) is a purely endoscopic method of myotomy with minimal invasiveness and a low rate of adverse events when performed by experienced operators. Since then, numerous studies have shown the significant clinical efficacy and safety of POEM. The purpose of this article is to introduce different modified POEMs, special indications for different POEMs, and their advantages as well as disadvantages.

Biliary spontaneous dislodgement spiral stent for patients who underwent mechanical lithotripsy.

BACKGROUND: The incidence of post-endoscopic retrograde cholangiopancreatography (ERCP) cholangitis (PEC) in patients who underwent mechanical lithotripsy (ML) for large stone removal is high (up to 13.3%). One of the main causes is remaining small fragments or sludge that can impair normal biliary drainage. Endoscopic placement of a nasobiliary tube or a conventional plastic biliary stent has been commonly used under such conditions, but the patient may suffer from significant discomfort after the placement of a nasobiliary tube, while additional endoscopy is required for stent removal. We developed a biliary spontaneous dislodgement spiral stent (BSDSS) to overcome those shortcomings. AIM: To evaluate the feasibility, safety, and effectiveness of inserting a BSDSS for patients who underwent ML for large stone removal. METHODS: We conducted a single-center, retrospective, cohort study at West China Hospital, Sichuan University. A total of 91 consecutive patients with large biliary stones (≥ 10 mm) in the common bile duct who underwent ML between November 2017 and July 2018 were included. The 49 eligible patients were divided into the BSDSS group and the nasobiliary tube group. Technical success, post-ERCP adverse events (including PEC, post-ERCP pancreatitis, stone recurrence, BSDSS retention, self-extraction and dislocation of the nasobiliary tube), drainage time, and postoperative stay were measured and compared. RESULTS: Twenty-one patients in the BSDSS group and 28 patients in the nasobiliary tube group were included in the analyses. The baseline characteristics and clinical information were similar in the two groups. Insertions of BSDSS and nasobiliary tube were technically successful in all 49 patients. There was no significant difference in the incidence of overall post-ERCP adverse events between the two groups (4.8% in the BSDSS group vs 17.9% in the nasobiliary tube group, P = 0.219). The median duration of drainage time (3 d in the BSDSS group vs 4 d in the nasobiliary tube group) and length of postoperative stay (4 d in the BSDSS group vs 5 d in the nasobiliary tube group) also did not differ (P = 0.934, and P = 0.223, respectively). CONCLUSION: Endoscopic placement of a BSDSS appears to be feasible, safe and effective for patients who underwent ML for large stone removal.

New antireflux plastic stent for patients with distal malignant biliary obstruction.

BACKGROUND: Endoscopic biliary stenting is a well-established palliative treatment for patients with unresectable distal malignant biliary obstruction (MBO). However, the main problem with stent placement is the relatively short duration of stent patency. Although self-expanding metal stents (SEMSs) have a longer patency period than plastic stents (PSs), the higher costs limit the wide use of SEMSs. A PS with an antireflux valve is an attractive idea to prolong stent patency, but no ideal design for an antireflux PS (ARPS) has been proposed. We developed a new ARPS with a "duckbilled" valve attached to the duodenal end of the stent. AIM: To compare the patency of ARPSs with that of traditional PSs (TPSs) in patients with unresectable distal MBO. METHODS: We conducted a single-center, prospective, randomized, controlled, double-blind study. This study was conducted at the West China Hospital of Sichuan University. Consecutive patients with extrahepatic MBO were enrolled prospectively. Eligible patients were randomly assigned to receive either an ARPS or a TPS. Patients were followed by clinic visits or telephone interviews every 1-2 mo until stent exchange, death, or the final study follow-up in October 2018. The primary outcome was the duration of stent patency. Secondary outcomes included the rate of technical success, the rate of clinical success, adverse events, and patient survival. RESULTS: Between February 2016 and December 2017, 38 patients were randomly assigned to two groups, with 19 patients in each group, to receive ARPSs or TPSs. Stent insertion was technically successful in all patients. There were no significant differences between the two groups in the rates of clinical success or the rates of early or late adverse events (P = 0.660, 1.000, and 1.000, respectively). The median duration of stent patency in the ARPS group was 285 d [interquartile range (IQR), 170], which was significantly longer than that in the TPS group (median, 130 d; IQR, 90, P = 0.005). No significant difference in patient survival was noted between the two groups (P = 0.900). CONCLUSION: The new ARPS is safe and effective for the palliation of unresectable distal MBO, and has a significantly longer stent patency than a TPS.

Intestinal ischemia-reperfusion of macaques triggers a strong innate immune response.

AIM: To investigate inflammatory injury in the intestinal mucosa after intestinal ischemia-reperfusion (IIR) with Toll-like receptor (TLR)-mediated innate immunity. METHODS: Ten macaques were randomized into control and IIR groups. The distribution and expression level of TLR2, TLR4, MD2, nuclear factor (NF)-κB p65 and interferon (IFN)-γ were measured by immunohistochemical stain and western blotting. The mRNA expression of TLR4, TLR2, MD2, interleukin (IL)-1ß and tumor necrosis factor (TNF)-α were measured by reverse transcriptase-polymerase chain reaction. The cytokine levels in blood and intestinal tissues were measured by ELISA. RESULTS: Obvious hemorrhage and erosion of mucosae were seen in the IIR group. Expression of TLR2, TLR4, MD2, NF-κB p65 and IFN-γ was significantly higher in the IIR group than in the control group (0.13 ± 0.04, 0.22 ± 0.04, 0.16 ± 0.06, 0.65 ± 0.12, 0.38 ± 0.10 vs 0.07 ± 0.04, 0.08 ± 0.03, 0.04 ± 0.02, 0.19 ± 0.06, 0.14 ± 0.05, P < 0.05). In addition, the expression of TLR2, TLR4, MD2, IL-1ß and TNF-α mRNA in the IIR group were significantly higher than those of control group(1.52 ± 0.15, 1.39 ± 0.06, 1.94 ± 0.12, 1.48 ± 0.15, 0.66 ± 0.08 vs 0.31 ± 0.05, 0.5 ± 0.04, 0.77 ± 0.05, 0.35 ± 0.08, 0.18 ± 0.04, P < 0.05). Furthermore, IL-1ß, IL-6 and TNF-α levels in the macaques ileum and plasma were significantly higher than in the control group (plasma: 86.3 ± 15.2, 1129 ± 248.3, 77.8 ± 16.2 vs 29.5 ± 7.3, 19.8 ± 8.2, 5.6 ± 1.7; ileum: 273.4. ± 44.7, 1636 ± 168.0, 205.5 ± 30.7 vs 76.8 ± 20.5, 663.4 ± 186.9, 49.0 ± 9.4; P < 0.05). CONCLUSION: After IIR, general inflammatory injury in the intestinal mucosa is correlated with a strong innate immune response, mediated by activation of the TLR-NF-κB-cytokine pathway.

cis-Tri-aqua-[1,1'-(propane-1,3-di-yl)bis-(pyridin-1-ium-4-carboxyl-ato)-κO]bis-(thio-cyanato-κN)manganese(II) dihydrate.

In the title compound, [Mn(NCS)2(C15H14N2O4)(H2O)3]·2H2O, the metal ion is octa-hedrally coordinated by three water mol-ecules, one carboxyl-ate O atom from a 1,1'-(propane-1,3-di-yl)bis-(pyridinium-4-carboxyl-ate) ligand and two N atoms from two thio-cyanate anions in cis positions, forming a mononuclear complex mol-ecule. In the crystal, mol-ecules are connected into a three-dimensional architecture through O-H⋯O hydrogen bonds involving water mol-ecules and carboxyl-ate groups.

[Somatostatin levels and polymorphonuclear neutrophil life in intestinal ischemia reperfusion of macaque].

OBJECTIVE: To investigate the association of somatostatin (SST) levels in plasma or jejunum tissue and polymorphonuclear neutrophil (PMN) life in intestinal ischemia reperfusion of macaque. METHODS: MODS model in macaque was established by clamping superior mesenteric artery. The levels of SST in plasma and jejunum tissue were measured by radioimmunoassay. After incubated with SST, the apoptotic PMN were determined by the morphological studies, flow cytometer and DNA agarose electrophoresis. The expression of SSTR on PMN was detected by biosensor. RESULTS: SST levels in macaque plasma or jejunum tissue were significantly decreased after intestinal ischemia reperfusion (IR) injury. The apoptotic rate of PMN was obviously reduced (15.4% +/- 1.4% to 3.5% +/- 0.5%, P < 0.05). However, the number of apoptotic macrophage from abdominal cavity was clearly increased. The apoptotic rate of PMN was significantly increased (20.0% +/- 2.2% to 50.2% +/- 1.8%, P < 0.01) after incubated with SST in vitro. Specific DNA ladder bands from PMN were visualized with agarose electrophoresis. Specific bindings between PMN and the antibodies for SSTR1 (548 RU/ml +/- 20 RU/ml) or SSTR2 (28 RU/ml +/- 21 RU/ml) were detected. CONCLUSION: The physiological apoptosis of PMN in macaque could be induced by SST through SSTRs on PMN. The decreased SST levels in macaque plasma or jejunum tissue in the state of intestinal ischemia reperfusion might extend PMN life and promote the occurrence of MODS.

[Changes of somatostatin and expression of somatostatin receptor in small intestine and liver tissues during macaque development].

Intestinal tract, which produces more than fifty kinds of gut peptides, is regarded as the largest endocrine organ. With regard to the gut peptides, a number of studies were focused on their structure, function and the roles in some diseases. The changes in output or distribution of gut peptides in the intestinal tract during development have been largely unknown. This study was aimed to investigate the changes of somatostatin (SST) and somatostatin receptor 2 (SSTR2) in small intestinal and hepatic tissues during the development of macaque. The tissue samples of small intestine, liver or blood samples from peripheral and portal vein of 4 macaques in 6-month fetus, 2-day neonate, 45-day neonate and adult were obtained after anesthetization. The concentrations of SST in blood or tissues of macaques were measured by radioimmunoassay. The distributions of SST in small intestinal or hepatic tissues were visualized by immunohistochemical staining. The expression of SSTR2 was detected by in situ hybridization. SST concentration of intestinal tissue in 6-month-old macaque was (27.3+/-16.6) ng /mg protein and light positive staining of SST was localized in mucosal crypts but negative in muscle layer. The intestinal concentration of SST increased gradually with macaque development and reached to the peak [(120.1+/-35.3) ng /mg protein] in adult. It was significantly higher than that in fetus (P<0.01). Strong positive staining of SST was found in both mucosal crypts and myenteric nerve plexus of adult animal. SSTR2 was obviously expressed in intestinal epithelium of fetus but its expression was greatly reduced in epithelium and was shifted to mucosal crypts when grown to adult. Negative staining of SSTR2 in muscle layer of fetal or neonatal macaque turned to be positive in myenteric nerve plexus of adult. The levels of SST or SSTR2 in liver decreased gradually during development. SST concentrations of small intestinal tissue kept significantly higher than those of hepatic tissues in the macaque developing stages. SST levels of portal vein were also maintained significantly higher than those of peripheral blood in the macaque developing stages. In conclusion, the level of SST and expression of SSTR2 in mucosal crypt increased gradually with macaque development. SST from intestinal tract was quickly degraded in portal vein before entering into liver. SST positive myenteric nerve plexus was visualized only in mature macaque.