Chemotherapy plus therapeutic plasmapheresis with 4% human albumin solution in multiple myeloma patients with acute kidney injury: a prospective, open-label, proof-of-concept study.

As no unified treatment protocol or evidence yet exists for plasmapheresis without plasma, this study explored the outcomes of using 4% human albumin (ALB) solution as a replacement solution in patients undergoing plasma exchange for multiple myeloma (MM) patients with acute kidney injury (AKI). This study was prospectively registered (ChiCTR2000030640 and NCT05251896). Bortezomib-based chemotherapy plus therapeutic plasmapheresis (TPP) with 4% human ALB solution was assessed for three years in patients with MM aged >18 years, with AKI according to the Kidney Disease Improving Global Outcomes criteria, and without previous renal impairment from other causes. The primary endpoints were changes in renal function over 18 weeks and survival outcomes at 36 months. The secondary endpoints were the incidence of adverse reactions and symptom improvement. Among the 119 patients included in the analysis, 108 experienced renal reactions. The M protein (absolute changes: median -12.12%, interquartile ranges (IQRs) -18.62 to -5.626) and creatine (median -46.91 µmol/L, IQR -64.70 to -29.12) levels decreased, whereas the estimated glomerular filtration rate (eGFR) increased (median 20.66 mL/(min·1.73 m2), IQR 16.03-25.29). Regarding patient survival, 68.1% and 35.3% of patients survived for >12 and >36 months, respectively. The three symptoms with the greatest relief were urine foam, poor appetite, and blurred vision. All 11 patients (7.6%) who experienced mild adverse reactions achieved remission. In conclusion, in MM patients with AKI, plasma-free plasmapheresis with 4% human ALB solution and bortezomib-based chemotherapy effectively alleviated light chain damage to kidney function while improving patient quality of life.

Association of total cholesterol with severe acute pancreatitis: A U-shaped relationship.

BACKGROUND & AIMS: There is no consensus on relationship between total cholesterol levels and incidence of severe acute pancreatitis (SAP). The aim of this study was to investigate the relation between total cholesterol (TC) and the disease severity of acute pancreatitis. METHODS: We conducted a cross-sectional study on patients with acute pancreatitis between April 2012 and December 2015 in a university hospital. Fasting blood total cholesterol (TC) was assayed within 24 h of admission, as well as 3-5 days, 7-9 days and 13-15 days during hospitalization. Time interval before admission, age, gender, Body Mass Index, hypertension, diabetes mellitus, alcohol consumption, smoking, etiology and albumin were recorded as potential confounding factors. To assess the pattern of relationship of TC and SAP, we used restricted cubic spline analysis with multivariable logistic regression analysis. We also compared total cholesterol concentrations between patients with or without SAP at different time points. RESULTS: 648 patients (median age: 47.5 years; 62.4% man) were enrolled. The incidence of SAP was 10%. A U-shaped association of TC level within 24 h of admission with severity was observed in acute pancreatitis. Patients with low TC levels (<160 mg/dL) and high TC levels (>240 mg/dL) had a significantly higher incidence of SAP and protracted hospital stays when compared to moderate TC levels (160-240 mg/dL). Low total cholesterol levels (OR 2.72; 95 %eCI 1.27-5.83; P = 0.01) and high total cholesterol levels (OR 2.54; 95 %eCI 1.09-5.89; P = 0.03), were still independently associated with development of SAP after adjusting for potential confounding factors. Longitudinal cohort study indicated that patients with SAP had lower total cholesterol concentrations among 3-15 days after admission compared to patients without SAP (P < 0.001). CONCLUSIONS: Both low TC level (<160 mg/dL) and high TC (>240 mg/dL) within 24 h of admission is independently associated with an increased risk of SAP.

In-situ generation of gold nanoparticles on MnO2 nanosheets for the enhanced oxidative degradation of basic dye (Methylene Blue).

In this work, the gold nanoparticles (Au-NPs) were in-situ generated on the surface of MnO2 nanosheets to form MnO2/Au-NPs nanocomposite in a simple and cost-effective way. Multiple experiments were carried out to optimize the oxidation of basic dye (Methylene Blue (MB)), including the molar ratio of MnO2 to chloroauric acid (HAuCl4), the pH of the solution and the effect of initial material. Under the optimal condition, the highest degradation efficiency for MB achieved to 98.9% within 60 min, which was obviously better than commercial MnO2 powders (4.3%) and MnO2 nanosheets (74.2%). The enhanced oxidative degradation might attribute to the in-situ generation of ultra-small and highly-dispersed Au-NPs which enlarged the synergistic effect and/or interfacial effect between MnO2 nanosheets and Au-NPs and facilitated the uptake of electrons by MnO2 from MB during the oxidation, thus validating the application of MnO2/Au-NPs nanocomposite for direct removal of organic dyes from wastewater in a simple and convenient fashion.

ARRDC4 regulates enterovirus 71-induced innate immune response by promoting K63 polyubiquitination of MDA5 through TRIM65.

Enterovirus 71 (EV71) is the main causative agent of hand, foot and mouth disease (HFMD), which induces significantly elevated levels of cytokines and chemokines, leading to local or system inflammation and severe complications, whereas the underlying regulatory mechanisms and the inflammatory pathogenesis remain elusive. ARRDC4 is one member of arrestins family, having important roles in glucose metabolism and G-protein-coupled receptors (GPCRs) related physiological and pathological processes, however, the function of ARRDC4 in innate immune system is largely unknown. Here we identified that ARRDC4 expression was increased after EV71 infection in THP-1-derived macrophages and verified in EV71-infected HFMD patients and the healthy candidates. The expression level of ARRDC4 was positively correlated with the serum concentration of IL-6, TNF-α and CCL3 in clinical specimens. ARRDC4 interacted with MDA5 via the arrestin-like N domain, and further recruited TRIM65 to enhance the K63 ubiquitination of MDA5, resulting in activation of the downstream innate signaling pathway and transcription of proinflammatory cytokines during EV71 infection. Our data highlight new function of ARRDC4 in innate immunity, contributing to the better understanding about regulation of MDA5 activation after EV71 infection, and also suggest ARRDC4 may serve as a potential target for intervention of EV71-induced inflammatory response.