Updated clinical and glycomic features of mannosyl-oligosaccharide glucosidase deficiency:Two case reports

BACKGROUND Mannosyl-oligosaccharide glucosidase(MOGS)deficiency is an extremely rare type of congenital disorder of glycosylation(CDG),with only 12 reported cases.Its clinical,genetic,and glycomic features are still expanding.Our aim is to update the novel clinical and glycosylation features of 2 previously reported patients with MOGS-CDG.CASE SUMMARY We collected comprehensive clinical information,and conducted the immunoglobulin G1 glycosylation assay using nano-electrospray ionization source quadruple time-of-flight mass spectrometry.Novel dysmorphic features included an enlarged tongue,forwardly rotated earlobes,a birth mark,overlapped toes,and abnormal fat distribution.Novel imaging findings included pericardial effusion,a deep interarytenoid groove,mild congenital subglottic stenosis,and laryngomalacia.Novel laboratory findings included peripheral leukocytosis with neutrophil predominance,elevated C-reactive protein and creatine kinase,dyslipidemia,coagulopathy,complement 3 and complement 4 deficiencies,decreased proportions of T lymphocytes and natural killer cells,and increased serum interleukin 6.Glycosylation studies showed a significant increase of hypermannosylated glycopeptides(Glc3Man7GlcNAc2/N2H10 and Man5GlcNAc2/N2H5)and hypersialylated glycopeptides.A compensatory glycosylation pathway leading to an increase in Man5GlcNAc2/N2H5 was indicated with the glycosylation profile.CONCLUSION We confirmed abnormal glycomics in 1 patient,expanding the clinical and glycomic spectrum of MOGS-CDG.We also postulated a compensatory glycosylation pathway,leading to a possible serum biomarker for future diagnosis.

Double Off-line Two-dimensional Liquid Chromatography for Separation and Identification of Compounds in Salvia Miltiorrhiza(Danshen)

Background: Danshen is an important traditional Chinese medicine(TCM) used for the treatment of cardiovascular and cerebrovascular diseases. Separation and analysis of its components have been widely investigated. However, the systematical two dimensional liquid chromatography(2D-LC) methods have not been developed to comprehensively separate and characterize its components.Objective: In this work, double off-line 2D-LC methods were aimed to develop for the systematical separation of compounds from Danshen.Methods: Using solid phase extraction(SPE), the Danshen extract was divided into a medium-polar fraction(Sample I) and a weak-polar fraction(Sample Ⅱ) according to their polarities. Based on reversed-phase liquid chromatography(RPLC) and hydrophilic interaction liquid chromatography(HILIC) modes, a 2D-HILIC × RPLC system and a 2D-RPLC × RPLC system were designed for the separation of Sample Ⅰ and Sample Ⅱ, respectively. According to reversed-phase and HILIC columns selectivities characterized in our previous reports, ZIC-HILIC and XTerra C18 were employed to build the 2D-HILIC × RPLC system and Click TE-CD and XTerra C18 for the 2D-RPLC × RPLC system,respectively.Results: The 2D-HILIC × RPLC and 2D-RPLC × RPLC systems exhibited excellent orthogonality for the separation of Sample Ⅰ and Sample Ⅱ,respectively. Their orthogonalities were 88.42% and 63.24%. Based on these double 2D-LC systems combined with mass spectrometry, at least 200 compounds were found and 33 compounds of them were identified, including 16 phenolic acids and 17 diterpenoid quinines.Conclusion: These results suggest that these two off-line 2D-LC methods are effective for the separation and characterization of components in Danshen.

Comprehensive Quality Evaluation of ShuXueNing Injection Employing Quantitative High-Performance Liquid Chromatography Fingerprint and Chemometrics

Objective:In this study,a comprehensive and effective quality method for evaluating the efficacy of ShuXueNing injection(SXNI)was developed.Materials and Methods:Quantitative high-performance liquid chromatography fingerprint,the quantitative analysis of multicomponents by a single marker(QAMS)method,hierarchical cluster analysis(HCA),and orthogonal partial least squares discrimination analysis(OPLS-DA)were used to distinguish 53 batches of SXNI samples from 7 manufacturers.Results:A total of 53 batches of samples were analyzed to establish antithesis fingerprint of SXNI,and 12 peaks of the common model were collected and used for the similarity analysis.Meanwhile,six index flavonoid components were determined by the QAMS method,using rutin as internal reference substance.The accuracy of the QAMS method was confirmed by investigating the relative deviation between the QAMS method and the traditional external standard method.The results demonstrated that there was no significant difference(RE<1%),suggesting that QAMS was a reliable and convenient method for the content determination of multiple components.The HCA and OPLS-DA methods drew a similar conclusion.The 53 batches of SXNI samples from 7 manufacturers were categorized into five groups,indicating that chemometrics could reveal the quality differences of SXNI between the manufacturers.Conclusions:The method established herein was efficient and successful in assessing the quality of SXNI,and that it may be potentially employed in the quality control of related products composed of Ginkgo biloba extract.