A report of a pedigree with compound heterozygous mutations in the SLC22A5 gene.

Introduction: To investigate the clinical characteristics and disease outcomes of a pedigree with compound heterozygous mutations in the SLC22A5 gene. Methods: Serum acylcarnitine profiles of patients were analyzed using tandem mass spectrometry. DNA samples isolated from patients and their first-degree relatives were subjected to high-throughput sequencing, and mutations were validated using Sanger sequencing. Results: The proband, a 4-month-old girl, presented with seizure episodes and mild cardiac hypertrophy and was diagnosed with primary carnitine deficiency (PCD), with carnitine levels of 5.165 mol/L. Her brother, a 6-year-and 4-month-old boy, was also diagnosed with PCD with serum-free carnitine levels of 1.014 mol/L (reference values 10-60 mol/L). Compound heterozygous mutations (c.760C > T [p.R254X] and c.825G > A [p.W275X]) were detected in the SLC22A5 gene in both patients and were inherited from the mother and father, respectively. Oral L-carnitine significantly improved or resolved the clinical symptoms. Conclusion: Children with compound mutations in SLC22A5 may present different clinical manifestations, particularly at different ages. Early clinical manifestations have a greater impact on the organs and may cause irreversible damage. PCD can cause epilepsy and dilated cardiomyopathy. Tandem mass spectrometry and high-throughput sequencing are recommended to confirm the diagnosis. Early L-carnitine supplementation can improve symptoms and reverse organ damage in some children. Tandem mass spectrometry should be used to screen for newborns with a family history of PCD.

Preventive effect of nicorandil on contrast-induced nephropathy: a meta-analysis of randomised controlled trials.

BACKGROUND: Contrast-induced nephropathy (CIN) is a common and serious side-effect in patients undergoing angiocardiography or radiological procedures. AIM: To assess comprehensively the impact of nicorandil on CIN, by gathering currently available data. METHODS: We searched three main electric databases (Medline/PubMed, EMBASE and Cochrane Central Register of Controlled Trials) from inception through April 2017. RESULTS: Four randomised controlled trials involving 730 participants were included. Pooled estimate showed that nicorandil significantly reduced the rate of CIN by 64% (risk ratio = 0.36, 95% confidence interval (CI): 0.22-0.61, I2 = 31%), compared with control. Nicorandil also significantly decreased serum creatinine level compared with control (mean difference (MD) = -2.70%, 95% CI: -5.21 to -0.20 for percentage change; and standard MD = -0.30, 95% CI: -0.48 to -0.13 for absolute change from baseline). In comparison to control, nicorandil was associated with a non-significant trend towards decreased cystatin C (MD = -2.18%, 95% CI: -4.39 to 0.02 for percentage change; and MD = -0.08 mg/dL, 95% CI: -0.24 to 0.09 mg/dL for absolute change from baseline). CONCLUSION: Nicorandil can protect renal function and reduce the incidence of CIN in patients exposed to contrast medium. Nicorandil is an additional option in preventing CIN.

Combination lung cancer chemotherapy: Design of a pH-sensitive transferrin-PEG-Hz-lipid conjugate for the co-delivery of docetaxel and baicalin.

The aim of the present study is to design a novel dual-ligand lipid based nanoparticle system. It is conducted by a specific ligand and pH sensitive lipid conjugate. Docetaxel (DTX) and baicalein (BA) are co-delivered by this system for combination lung cancer chemotherapy. Firstly, transferrin (Tf)-polyethylene glycol (PEG)-hydrazone (hz)-glyceryl monostearate (GMS), Tf-PEG-hz-GMS, was synthesized. Tf decorated DTX and BA loaded solid lipid nanoparticles (Tf-D/B-SLNs) were prepared by emulsification method. The capability of Tf-D/B-SLNs in suppressing lung cancer cells in vitro and in vivo was investigated. The results revealed the better antitumor efficiency of Tf-D/B-SLNs than the non-decorated SLNs and single drug loaded SLNs. Significant synergistic effects were observed in the dual drugs loaded systems. The best tumor inhibition ability and the lowest systemic toxicity also proved the pH-sensitive co-delivery nano-system could be a promising strategy for treatment of lung cancer.

Metabolic profile and pharmacokinetics of polyphyllin I, an anticancer candidate, in rats by UPLC-QTOF-MS/MS and LC-TQ-MS/MS.

Polyphyllin I (PPI), a natural steroidal saponin originating from rihzome of Paris polyphylla, is a potential anticancer candidate. Previous pharmacokinetics study showed that the oral bioavailability of PPI was very low, which suggested that certain amount of PPI might be metabolized in vivo. However, to date, information regarding the final metabolic fates of PPI is very limited. In this study, metabolites of PPI and their pharmacokinetics in rats were investigated using UPLC-QTOF-MS/MS and LC-TQ-MS/MS. A total of seven putative metabolites, including six phase I and one phase II metabolites, were detected and identified with three exact structures by comparison with authentic standards for the first time. Oxidation, deglycosylation and glucuronidation were found to be the major metabolic processes of the compound in rats. The pharmacokinetics of prosapogenin A, trillin and diosgenin, three deglycosylation metabolites of PPI with definite anticancer effects, were further studied, which suggested that the metabolites underwent a prolonged absorption and slower elimination after intragastric administration of PPI at the dose of 500 mg/kg. This study provides valuable and new information on the metabolic fate of PPI, which will be helpful in further understanding its mechanism of action.

MnO2/CeO2 for catalytic ultrasonic decolorization of methyl orange: Process parameters and mechanisms.

MnO2/CeO2 catalyst was prepared and characterized by means of Brunauer-Emmet-Teller (BET) method, X-ray diffraction (XRD) and scanning electron microscope (SEM). The characterization showed that MnO2/CeO2 had big specific surface area and MnO2 was dispersed homogeneously on the surface of CeO2. Excellent degradation efficiency of methyl orange was achieved by MnO2/CeO2 catalytic ultrasonic process. Operating parameters were studied and optimized. The optimal conditions were 10 min of ultrasonic irradiation, 1.0 g/L of catalyst dose, 2.6 of pH value and 1.3 W/ml of ultrasonic density. Under the optimal conditions, nearly 90% of methyl orange was removed. The mechanism of methyl orange degradation was further studied. The decolorization mechanism in the ultrasound-MnO2/CeO2 system was quite different with that in the ultrasound-MnO2 system. Effects of manganese and cerium in catalytic ultrasonic process were clarified. Manganese ions in solution contributed to generating hydroxyl free radical. MnO2/CeO2 catalyst strengthened the oxidation ability of ultrasound and realized complete decolorization of methyl orange.