Pathogenesis and treatment of non-alcoholic steatohepatitis and its fibrosis

The initial presentation of non-alcoholic steatohepatitis (NASH) is hepatic steatosis. The dysfunction of lipid metabolism within hepatocytes caused by genetic factors, diet, and insulin resistance causes lipid accumulation. Lipotoxicity, oxidative stress, mitochondrial dysfunction, and endoplasmic reticulum stress would further contribute to hepatocyte injury and death, leading to inflammation and immune dysfunction in the liver. During the healing process, the accumulation of an excessive amount of fibrosis might occur while healing. During the development of NASH and liver fibrosis, the gut-liver axis, adipose-liver axis, and renin-angiotensin system (RAS) may be dysregulated and impaired. Translocation of bacteria or its end-products entering the liver could activate hepatocytes, Kupffer cells, and hepatic stellate cells, exacerbating hepatic steatosis, inflammation, and fibrosis. Bile acids regulate glucose and lipid metabolism through Farnesoid X receptors in the liver and intestine. Increased adipose tissue-derived non-esterified fatty acids would aggravate hepatic steatosis. Increased leptin also plays a role in hepatic fibrogenesis, and decreased adiponectin may contribute to hepatic insulin resistance. Moreover, dysregulation of peroxisome proliferator-activated receptors in the liver, adipose, and muscle tissues may impair lipid metabolism. In addition, the RAS may contribute to hepatic fatty acid metabolism, inflammation, and fibrosis. The treatment includes lifestyle modification, pharmacological therapy, and non-pharmacological therapy. Currently, weight reduction by lifestyle modification or surgery is the most effective therapy. However, vitamin E, pioglitazone, and obeticholic acid have also been suggested. In this review, we will introduce some new clinical trials and experimental therapies for the treatment of NASH and related fibrosis

Frequency-Synthesized Approach to High-Power Attosecond Pulse Generation and Applications: Applications

In part I of this work, we present the design, construction and diagnostics of a new scheme of generating high-power attosecond pulses and arbitrary waveforms by multicolor synthesis. In this chapter, we demonstrate selected applications of this novel source, such as coherently controlled harmonic generation as well as phase-sensitive two-color ablation of copper and stainless steel by this multicolor laser system

Outcome for self-expandable metal stents in patients with malignant gastroduodenal obstruction: A single center experience

SummaryBackgroundMalignant gastric outlet obstruction causes significant malnutrition and morbidity. The implantation of a metallic stent is an alternative palliative treatment to allow the intake of food in these patients.Patients and MethodsThirty-eight consecutive patients with malignant gastric outlet obstruction who had received an uncovered metallic stent placement in our department from April 2010 to April 2012 were enrolled for analysis. The mean follow-up time was 6.3 months. Food intake, measured by the Gastric Outlet Obstruction Scoring System, complications, duration of stent patency, and survival were evaluated.ResultsThe technical and clinical success rates of the procedure were 100% and 94.7%, respectively. The Gastric Outlet Obstruction Scoring System scores were significantly improved at 1 day, 7 days, and 30 days after the implantation compared with those prior to the procedure (p < 0.001). Aspiration pneumonia developed in two patients (5.2%) after the procedure. One of these patients developed respiratory failure and died 3 days later. Stent dysfunction developed in 11 of 38 patients (28.9%) during the follow-up period; one patient (2.6%) experienced migration of the stent 38 days later due to resolution of the stricture; 10 patients (26.3%) had stent restenosis. The median time of stent patency was 120 days. The presence of peritoneal carcinomatosis when the procedure was carried out was a significantly poor predictive factor of stent patency [hazard ratio (HR) 7.9, p = 0.039]. The median survival of the patients was 156 days. Poor performance status ≥3; HR 2.647, p = 0.012) and nongastric cancer origin (HR 3.466, p = 0.008) were associated with a significantly short survival time.ConclusionMetallic stent placement is an effective and relatively safe treatment for patients with malignant gastric outlet obstruction

New material of alagomyids

29 p. : ill. ; 26 cm.Includes bibliographical references (p. 26-29).Newly discovered specimens of alagomyids, mostly isolated teeth collected by screenwashing at the Gashatan (late Paleocene) Subeng locality in Inner Mongolia, document considerable intraspecific variation in Tribosphenomys minutus that has not been appreciated previously because of limited sample sizes. P4s of Tribosphenomys are described for the first time, which helps to clarify the posterior premolar identification of alagomyids. Some of the alagomyid specimens are referred to Tribosphenomys cf. T. secundus and Neimengomys qii gen. and sp. nov. Based on the new data, Tribosphenomys borealis from the Bumban Member of the Naran Bulak Formation, Mongolia, is considered to be a junior synonym of Alagomys inopinatus, and T. tertius from the Zhigden Member of the Naran Bulak Formation is regarded as a junior synonymof T. minutus. Alagomyidae, consisting of Tribosphenomys, Alagomys and Neimengomys, is maintained as a valid family. The presence of a diversity of alagomyids and other recently obtained fossils and stratigraphic evidence from the Erlian Basin suggest that the Gashatan and Bumbanian of Asia are probably correlative to the late Tiffanian-early Wasachian of North America. The faunal turnover during the Gashatan and Bumbanian in Asia is probably related to the late Paleocene-early Eocene global warming, but current evidence is insufficient to link any specific event with the Paleocene-Eocene Thermal Maximum

Screening and Evaluation of Polyhydroxybutyrate-Producing Strains from Indigenous Isolate Cupriavidus taiwanensis Strains

Polyhydroxyalkanoate (PHA) is a biodegradable material with many potential biomedical applications, including medical implants and drug delivery. This study developed a system for screening production strains in order to optimize PHA production in Cupriavidus taiwanensis 184, 185, 186, 187, 204, 208, 209 and Pseudomona oleovorans ATCC 29347. In this study, Sudan black B staining, Infrared (IR) and Gas Chromatography (GC) analysis indicated that the best strain for PHA synthesis is C. taiwanensis 184, which obtains polyhydroxybutyrate (PHB). Cultivation of C. taiwanensis 184 under a pH of 7.0, at 30 °C, and at an agitation rate of 200 rpm, obtained a PHB content of 10% and PHB production of 0.14 g/L. The carbon and nitrogen types selected for analysis of PHB production by C. taiwanensis 184 were gluconic acid and NH4Cl, respectively. Optimal carbon/nitrogen ratio for PHB production was also determined. This study demonstrated a PHB content of 58.81% and a PHB production of 2.44 g/L when the carbon/nitrogen ratio of 8/1 was selected for C. taiwanensis 184. A two-stage fermentation strategy significantly enhanced PHB content and PHB production. Under a two-stage fermentation strategy with nutrient-limited conditions, C. taiwanensis 184 obtained a PHB content of 72% and a PHB concentration of 7 g/L. Finally, experimental results confirmed that optimizing the growth medium and fermentation conditions for cultivating the indigenous C. taiwanensis 184 strain substantially elevated PHB content from 10% to 72% and PHB production from 0.14 g/L to 7 g/L, respectively

Gastric Necrosis and Perforation as a Severe Complication of Pancreatic Pseudocyst

Patients with acute pancreatitis may present with stress-related gastrointestinal mucosal lesions. But severe gastrointestinal complications such as gastric perforation are very rare. Here, we report a 40-year-old man who was admitted due to acute pancreatitis and pseudocyst formation. During hospitalization, panendoscopic examination found multiple scattered stress ulcers over the gastric antrum and a large ulcerative area with suspicious malignant features at the body and fundus. The patient received surgical intervention due to worsening of his clinical condition. Postoperative findings showed a perforation of the gastric wall at the region in contact with the pseudocyst, and microscopic examination found diffuse ischemia and necrosis with intravascular thrombus and emboli in gastric vessels. We suggest keeping in mind that pancreatic pseudocyst may cause serious gastrointestinal complications including massive necrosis and perforation of the gastric wall

Primary Small Cell Carcinoma of the Stomach Successfully Treated With Cisplatin and Etoposide

We report a 44-year-old man with primary gastric small cell carcinoma who showed a remarkable response to chemotherapy specific for pulmonary small cell carcinoma. The patient had been admitted to another local hospital because of intermittent epigastralgia. An upper gastrointestinal examination there revealed an ulcerative tumor, 5 cm in diameter, on the lesser curvature side of the cardia, and endoscopic biopsy reported adenocarcinoma. Computed tomography revealed a mass over the lesser curvature of the stomach and some enlarged regional lymph nodes. Radical total gastrectomy, lymph node dissection, Roux-en-Y esophagojejunostomy and splenectomy were performed at our hospital. Pathology revealed gastric mucosa infiltrated by small-sized tumor cells with scanty cytoplasm and hyperchromatic nuclei. Immunohisto- chemically, the tumor cells were positive for synaptophysin, chromogranin A, and CD56. Primary gastric small cell carcinoma was diagnosed. The postoperative course, complicated by shock due to bleeding, wound infection and intra-abdominal abscess, took more than 2 months to resolve. Follow-up computed tomography showed tumor recurrence with multiple enlarged lymph nodes in the aortocaval region and hepatic hilum. The patient received palliative chemotherapy consisting of cisplatin 80 mg/m2 on day 1 and etoposide 80 mg/m2 on days 1–3 every 28 days, and had partial response to the chemotherapy, with a progression-free survival of 10 months. Chemotherapy with cisplatin and etoposide used for small cell carcinoma of the lung is a good treatment for gastric small cell carcinoma