Lactulose regulates gut microbiota dysbiosis and promotes short-chain fatty acids production in acute pancreatitis patients with intestinal dysfunction.

BACKGROUND: Intestinal dysfunction is one of the common complications in the early stage of acute pancreatitis (AP), which often associates with bad outcome. Lactulose, as a prebiotic, has been widely used to improve gut health, yet its effect on AP is unclear. METHODS: This was a prospective, randomized trial of moderate severe AP patients complicated with intestinal dysfunction. A total of 73 participants were randomly assigned to receive either lactulose or Chinese herb rhubarb for 1 week. The primary efficacy endpoint was the recovery of intestinal function. The serum levels of inflammatory cytokines and gut barrier indexes were examined. The fecal samples from patients before and after treatment were collected. 16 S rRNA gene sequencing analysis was performed to explore the composition of gut microbiota and the amount of short-chain fatty acids (SCFAs) were detected by gas chromatography-mass spectrometry (GC-MS). RESULTS: The intestinal dysfunction was prominently improved after 7 days of treatment with either lactulose or rhubarb. The serum levels of cytokines and gut permeability index were decreased after treatment, with stronger down-regulated degree in lactulose group than rhubarb. The potential beneficial genus Bifidobacterium was enriched in lactulose group, while pathogenic bacteria including Escherichia-Shigella and Neisseria were abundant in rhubarb group. Of note, the level of SCFAs was remarkably increased after treatment, with higher amount in lactulose group than rhubarb group. CONCLUSIONS: Lactulose could not only restore intestinal function but also regulate gut microbiota and promote the production of SCFAs.

Dynamic Changes and Nomogram Prediction for Sinistral Portal Hypertension in Moderate and Severe Acute Pancreatitis.

Objectives: To investigate the dynamic changes in gastric varices in patients with acute pancreatitis (AP) and to develop a novel nomogram for the early prediction of sinistral portal hypertension (SPH). Methods: This was a retrospective, case-control study with an analysis of the quantitative, dynamic computed tomography imaging results of SPH in patients with moderate and severe AP with a long-term follow-up. Multivariate logistic regression analysis and nomogram were employed. Results: The SPH group (n = 94) and non-SPH group (n = 94) were matched. The dynamic changes showed an increasing trend in the diameter of gastric fundus, short gastric, gastric coronary, and gastroepiploic veins, which did not recover during the one-year follow-up. Multivariate analysis showed that male (adjusted odds ratio (adjOR), 8.71; 95% confidence interval (CI), 2.86-26.53; P < 0.001), body mass index ≥27.5 kg/m2 (adjOR, 5.49; 95% CI, 1.85-16.29; P = 0.002), prothrombin time ≥12.6 s (adjOR, 2.82; 95% CI, 1.11-7.17; P = 0.03), and the patency of splenic vein [stenosis (adjOR, 8.48; 95% CI, 2.13-33.71; P = 0.002), and occlusion (adjOR, 34.57; 95% CI, 10.87-110.00; P < 0.001)] were independently associated with the development of SPH. The nomogram incorporating these factors demonstrated good discrimination, calibration and clinical utility. The area under the curve was as high as 0.92 (95% CI, 0.87-0.95). Conclusion: The dynamic changes in varices in SPH are long-term and slowly progressing. Males and obese patients with abnormal splenic veins and coagulopathies are at high risk for developing SPH. A simple nomogram tool helps in the early, accurate prediction of SPH.

A global agenda for advancing freshwater biodiversity research.

Global freshwater biodiversity is declining dramatically, and meeting the challenges of this crisis requires bold goals and the mobilisation of substantial resources. While the reasons are varied, investments in both research and conservation of freshwater biodiversity lag far behind those in the terrestrial and marine realms. Inspired by a global consultation, we identify 15 pressing priority needs, grouped into five research areas, in an effort to support informed stewardship of freshwater biodiversity. The proposed agenda aims to advance freshwater biodiversity research globally as a critical step in improving coordinated actions towards its sustainable management and conservation.

Circulating levels of thrombopoietic and inflammatory cytokines in patients with acute myeloblastic leukemia and myelodysplastic syndrome.

BACKGROUND: The regulation of megakaryocytopoiesis and thrombopoiesis appears to be under the control of an array of hematopoietic growth factors. The regulatory mechanism of endogenous cytokines in circulating platelet counts of thrombocytopenic patients with acute myeloblastic leukemia (AML) and myelodysplastic syndrome (MDS) is still not clear. METHODS: We measured the serum levels of both thrombopoietic and inflammatory cytokines in peripheral blood and bone marrow samples collected from 52 patients with either AML or MDS along with 35 normal control samples. The levels of thrombopoietin (TPO), interleukin (IL)-11, IL-6, IL-8 and stem cell factor (SCF) were determined by ELISA. RESULTS: Platelet counts in the AML/MDS patients during initial diagnosis, chemotherapy and complete remission were 71.2 +/- 11.6, 47.2 +/- 6.1 and 181.4 +/- 26.3 x10(9)/l, respectively. The median value of TPO in AML/MDS patients during diagnosis was 150.6 pg/ml and increased significantly during chemotherapy (median: 828 pg/ml; p < 0.05) but then decreased following complete remission (median: 221.4 pg/ml). However, these levels were all significantly higher in patients than in normal subjects (p < 0.05, p < 0.05 and p < 0.05; respectively), and no significant change was noted in the levels of IL-11 and SCF during treatment of patients or in normal controls. The level of IL-6 was not detectable in normal serum samples but was markedly increased in the AML/MDS patients (median level during diagnosis: 6.7 pg/ml; chemotherapy: 25 pg/ml; complete remission: 7 pg/ml). The level of IL-8 in patients with AML and MDS was markedly elevated during diagnosis (median: 27.5 pg/ml; range: 0-1,587 pg/ml), but decreased to the level of the normal controls when patients were under chemotherapy or in complete remission. CONCLUSIONS: The endogenous levels of TPO, IL-6 and IL-8 are elevated in the thrombocytopenic patients with AML and MDS. Our results are consistent with previous mechanistic studies and suggest that TPO and IL-6 may be active mediators of platelet production.