Niemann-Pick disease type C (NPC) is a lysosomal storage disease characterized by abnormal accumulation of free cholesterol and glycolipids. Here, we established induced pluripotent stem cell (iPSC) lines from NPC patients. Hepatocyte-like cells (HLCs) and neural progenitors derived from the iPSC lines accumulated cholesterol and displayed impaired autophagy and ATP production. A molecular signature related to lipid metabolism was also impaired in the NPC-iPSCderived HLCs. These findings indicate that iPSC-derived cells can phenocopy human NPC. We also newly found that 2-hydroxypropyl-c-cyclodextrin (HPGCD) could reduce the cholesterol accumulation and restore the functional and molecular abnormalities in the NPC patientderived cells, and do so more effectively than 2-hydroxypropyl-b-cyclodextrin treatment. In addition, NPC model mice showed an improved liver status and prolonged survival with HPGCDs. Thus, iPSC lines derived from patient cells are powerful tools to study cellular models of NPC, and HPGCD is a potential new drug candidate for future treatment of this disease.

Background and study aims: Feeding-related adverse events after percutaneous endoscopic gastrostomy (PEG) such as aspiration pneumonia may result in prolonged hospitalization and postoperative mortality. This study evaluated the efficacy of using semi-solid feeds to reduce feeding-related adverse events and improve clinical outcomes. Patients and methods: Patients who received PEG for enteral nutrition at our hospital between January 2014 and December 2015 were allocated to a postoperative feeding protocol that used either liquid feed or semi-solid feed. Baseline characteristics, postoperative feeding-related adverse events and clinical outcomes in the 2 groups were prospectively analysed and compared. Results: One hundred and seventeen PEG patients (age range: 59 – 97 years, male: 53) were enrolled with 72 patients given liquid feed and 45 patients receiving semi-solid feed. Baseline characteristics were similar in both groups. The semi-solid feed group experienced fewer incidence of feeding-related aspiration pneumonia (2.2 % vs. 22.2 %, P < 0.005) and shorter postoperative hospital length of stay (12.7 days vs. 18.8 days, P < 0.01). Significant differences were not observed in the frequency of peristomal infection (11.1 % vs. 12.5 %, P = 0.82), feeding-related diarrhea (2.2 % vs. 12.5 %, P = 0.09) and 30-day mortality rates (2.2 % vs. 8.3 %, P = 0.25). Conclusions: Semi-solid feeding may reduce the risk of aspiration pneumonia and shorten postoperative hospital length of stay after PEG. Semi-solid feeds are safe to use and can be employed either as a first line feeding protocol or an alternative when liquid feeding is unsuccessful.

Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) was originally reported as a responsible gene for generalized arterial calcification in infancy (GACI). Though the prognosis of GACI patients is poor because of myocardial infarction and heart failure in relation to medial calcification of the coronary arteries, some patients rescued by bisphosphonate treatment have been reported. Recently, ENPP1 is also reported as responsible for autosomal recessive hypophosphatemic rickets type 2. We show here a boy with homozygous ENPP1 mutations diagnosed as having GACI in early infancy. After the diagnosis, he was treated with etidronate disodium (EHDP) in combination with antihypertensive drugs. The calcification of major arteries was diminished and disappeared by the age of eight months. He also showed mild hypophosphatemia (2.6–3.7 mg/dl) from the age of one year. After the treatment with EHDP for five years, he showed genu valgum with hypophosphatemia (2.6 mg/dl). He was diagnosed as having hypophosphatemic rickets at the age of seven years. The findings that hyper-mineralization of the arteries and hypo-mineralization of the bone observed in the same patient are noteworthy. ENPP1 could be regarded as a controller of the calcification of the whole body at least in part.

Background and study aims: Percutaneous endoscopic gastrostomy (PEG) using the introducer technique is not only useful in patients with upper digestive tract stenosis but has been shown to reduce peristomal infection. In this study, we evaluated the safety and utility of a novel large-caliber introducer PEG kit (using 20 Fr size tube) compared with a push kit of similar size. Patients and methods: One hundred and thirty-six patients who received PEG at our hospital between January 2014 and December 2015 were retrospectively analyzed. Baseline characteristics, laboratory biomarkers, hemodynamic changes, postoperative adverse events and clinical outcomes with both kits were compared. Results: The new introducer PEG kit was used in 61 patients while the remaining 75 patients received tube placement using a push technique PEG kit. Except for the prevalence of dementia, which was lower in the introducer PEG kit group, baseline characteristics were similar in both groups. Tube placements were 100 % successful with both PEG kits and there were no significant differences in the change of postoperative hemodynamic or laboratory biomarkers. The Introducer PEG kit group experienced fewer incidence of feeding-related aspiration pneumonia (8.2 % vs. 24 %, P = 0.02), lower peristomal infection scores (1.2 vs. 1.6, P < 0.01), shorter postoperative length of stay (16 days vs. 23.7 days, P = 0.01) and fewer deaths at day 60 (3.3 % vs. 16 %, P = 0.02). Conclusions: Gastrostomy using the new large-caliber introducer PEG kit is safe and produced non-inferior (with some favourable) results when compared to the push technique using similar size tubes.

We propose that examination of INF2 expression may help to differentiate MCD from FSGS and evaluate the clinical severity of SRNS in children.

Background/aimsAlthough percutaneous endoscopic gastrostomy (PEG) is the method of choice for long-term enteral nutrition, feeding-related adverse events such as aspiration pneumonia and peristomal leakage can impede the use of PEG. Percutaneous endoscopic transgastric jejunostomy (PEG-J) using large-bore jejunal tubes may help by circumventing gastric passage during enteral nutrition and improving drainage of gastric secretions.Methods20 patients (12 males and 8 females) who received PEG-J after unsuccessful PEG feeding during a 6-year period in our institution were analysed retrospectively to evaluate the efficacy of large-bore jejunal feeding tubes in maintaining enteral nutrition.ResultsThe median age was 83.5 (71–96) years. The median period between PEG and PEG-J was 33 (14–280) days. Indications were aspiration due to gastro-oesophageal reflux in 18 patients and severe peristomal leakage in 2 patients. Tube placements were successful in all patients. There were 6 (30%) in-hospital mortalities, with 3 (15%) occurring within 30 days after procedure.ConclusionsPEG-J can be performed safely in patients with PEG and may facilitate the maintenance of enteral nutrition in most of the patients. Patients with unsuccessful PEG feeding can be offered the option of jejunal feeding before considering termination of enteral nutrition.

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xenograft tumor model was introduced to investigate the role of OLA1 in vivo. Results OLA1 demonstrated a higher expression in gastric cancer tissues with stage III-IV compared to paired normal tissue (25 paired sample; P<0.001), and the high level of OLA1 was correlated with poor prognosis (HR=2.40, P=0.008) and decreased sensitivity to 5-fluorouracil adjuvant chemotherapy (HR=2.63, P<0.001). Overexpression of OLA1 in gastric cancer cells reduced the sensitivity to 5-fluorouracil treatment, while knockdown of OLA1 by shRNA in gastric cancer cells significantly inhibited the cell proliferation, migration, invasion and tumorigenicity. However, OLA1 did not affect the cell cycle and proliferation in normal gastric epithelium cells. Mechanistically, WGCNA analysis of TCGA RNA-seq data suggested that high expression of OLA1 will promote G2/M phase transition and eventually lead to tumor progression, while knockdown of OLA1 in gastric cancer cells significantly prolonged G2/M phase (control vs KD: 10.65% vs 21.59%; P<0.01). Conclusions OLA1 inhibition could suppress gastric cancer progression and enhance the sensitivity to adjuvant chemotherapy with sparing normal gastric epithelium cells. Therefore, OLA1 could be a novel and promising target in treating gastric cancer.