Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease with a 5-year survival rate of less than 8%. To date, there are no early detection methods or effective treatments available. Many questions remain to be answered in regards to the pathogenesis of PDAC, among which, the controversy over the cell lineage of PDAC demands more attention. Ductal cells were originally thought to be the cell of origin for PDAC due to the ductal morphology of most cases of PDAC. However, recent studies have demonstrated that acinar cells are more sensitive to KRAS mutation and tend to develop to PanIN and PDAC effectively, very likely by undergoing acinar to ductal metaplasia into a transient state that contributes to PDAC initiation. There is also evidence that both ductal and acinar cells can potentially develop to PDAC when exposed to certain genetic settings and stimuli, suggesting that more scrutiny is required for the identification of the true cell lineage of individual cases of PDAC. In this work, we summarize recent findings in the identification of the cellular origin of PDAC, with the goal of advancing our knowledge on the initiation and progression of the disease. We also discuss various models and techniques for investigating early events of PDAC. Better understanding of these cellular events is crucial to identify new methods for the early diagnosis and treatment of PDAC.

Objectives: The results of previously published meta-analyses showed that dietary fiber could reduce the levels of p-cresyl sulfate, blood urea nitrogen, and creatinine in patients with chronic kidney disease (CKD). However, these results were based on some trials with pre-post design and randomized controlled trials of low quality. Additionally, it has been suggested that the dosage and duration of fiber supplementation and patients' characteristics potentially influence the effect of dietary fiber in reducing uremic toxins, but it would appear that no research has provided reliable evidence.Design and Methods: We searched PubMed, Web of Science, and Cochrane Library. Data were pooled by the generic inverse variance method using random effects models and expressed as standardized mean difference (SMD) with 95% confidence interval (CI). Heterogeneity was quantified by I 2 . Publication bias was evaluated by Egger's test.Results: Ten randomized controlled trials involving 292 patients with CKD were identified. Dietary fiber supplementation can significantly reduce the levels of indoxyl sulfate (

Previously we reported that the expression of promyelocytic leukemia (PML)-retinoic acid receptor alpha (RARα) fusion gene, which is caused by specific translocation (15;17) in acute promyelocytic leukemia, can enhance constitutive autophagic activity in leukemic and nonleukemic cells, and PML overexpression can sequestrate part of microtubule-associated protein light chain 3 (LC3) protein in PML nuclear bodies, suggesting that LC3 protein also distributes into nuclei although it is currently thought to function primarily in the cytoplasm, the site of autophagosomal formation. However, its potential significance of nucleoplasmic localizations remains greatly elusive. Here we demonstrate that PML interacts with LC3 in a cell type-independent manner as assessed by Co-IP assay and co-localization observation. Overexpressed PML significantly coprecipitates with endogenous and nuclear LC3 protein. Furthermore, a fraction of endogenous PML protein is found to be co-localized with LC3 protein under steady state condition, which is further enhanced by IFNα induction, indicating that PML up-regulation potentiates this interaction. Additionally, DsRed-PML associates with EGFP-LC3 during telophase and G1 phase but not in metaphase and anaphase. Two potential LC3-interacting region (LIR) motifs in PML are required for interaction of PML with LC3 while this association is independent of autophagic activity. Finally, we show that interaction between PML and LC3 contributes to cell growth inhibition function of PML. Considering that PML is an important tumor suppressor, we propose that nuclear portion of LC3 protein may associate with PML to control cell growth for prevention and inhibition of cancer occurrence and development.

Acquired haemophilia A (AHA) is a rare bleeding disorder with a high potential for severe bleeding and an inhibitor-related mortality rate of 7.9-22%, which might be associated with pregnancy, autoimmune diseases, malignancy, infections or medication and occurs most commonly in the elderly. Effective treatment of actual bleeding episodes and eradication of Factor VII inhibitor are the two important aspects in treatment [1]. Here, we present an AHA case that was successfully treated with a combination of low-dose rituximab and recombinant human FVII a (rh FVIIa).A 58-years-old man was admitted for intramuscular bleeding. Lab tests showed a prolonged activated partial thromboplastin time (APTT) of 93.2 s, FVIII level less than 1% and FVIII inhibitor titre of 21.8 BU. No evidence of malignancy, tuberculosis or autoimmune disorders was found. The patient did not take any new drug before admission. Moreover, an acquired von Willebrand's disease was excluded with normal vWF:Ag and vWF:Rco. Mixture of the patient's plasma with normal control plasma did not correct the prolonged APTT. Based on clinical manifestation and lab tests, AHA was diagnosed. Intramuscular bleeding progressed with rapid fall of haemoglobin. Fresh plasma, human FVIII and prothrombin complex concentrates injection did not alleviate bleeding. Bleeding was resolved following infusion with rh FVIIa (90 lg kg À1 3 h À1 9 8 times). Prednisone (0.8 mg kg À1 day À1 ) and Cyclophosphamide (CTX) (0.4 g 4 days À1 9 4 times) was given on day 1 while the FVIII remained less than 1% and the FVIII inhibitor titre >14 BU for the next 2 weeks. Low dose of rituximab (100 mg week À1 9 4 weeks) was administrated on day 11, and the antibodies were progressively decreased and finally disappeared on day 21. Oral Cyclosporine (250 mg day À1 ) plus prednisone (0.5 mg kg À1 day À1 ) were given outside hospital and serum level of CSA (150-250 ng mL À1 ) was monitored to avoid side effect. With 7 months follow-up, the patient showed no antibodies and normal FVIII (range 60-98%) with oral cyclosporine (100 mg day À1 ). (Fig. 1).AHA occurs as a result of auto-antibodies against coagulation factor VIII (FVIII) which neutralize its procoagulant function and lead to life-threatening bleeding. Approximately 50% of the patients are idiopathic with no known underlying pathological conditions. Clinical manifestations include spontaneous haemorrhages into the skin, muscles or soft tissues or excessive bleeding during surgery. The diagnosis of AHA is based on the isolated prolongation of APTT which is not normalized after the addition of normal plasma along with reduced FVIII levels. Early therapy directed towards achieving haemostasis and inhibitor eradication can be life saving [2].