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Recently, increasing attention has been paid to diabetic encephalopathy, which is a frequent diabetic complication and affects nearly 30% of diabetics. Because cognitive dysfunction from diabetic encephalopathy might develop into irreversible dementia, early diagnosis and detection of this disease is of great significance for its prevention and treatment. This study is to investigate the early specific metabolites biomarkers in urine prior to the onset of diabetic cognitive dysfunction (DCD) by using metabolomics technology. An ultra-high performance liquid-chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-Q/TOF-MS) platform was used to analyze the urine samples from diabetic mice that were associated with mild cognitive impairment (MCI) and nonassociated with MCI in the stage of diabetes (prior to the onset of DCD). We then screened and validated the early biomarkers using OPLS-DA model and support vector machine (SVM) method. Following multivariate statistical and integration analysis, we found that seven metabolites could be accepted as early biomarkers of DCD, and the SVM results showed that the prediction accuracy is as high as 91.66%. The identities of four biomarkers were determined by mass spectrometry. The identified biomarkers were largely involved in nicotinate and nicotinamide metabolism, glutathione metabolism, tryptophan metabolism, and sphingolipid metabolism. The present study first revealed reliable biomarkers for early diagnosis of DCD. It provides new insight and strategy for the early diagnosis and treatment of DCD.

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Background Haploidentical transplantation has been proposed as an effective treatment for severe aplastic anemia (SAA). The majority of patients have more than one HLA-haploidentical donor. Herein, we compared the outcomes between different donor-recipient relationships for optimal haploidentical donor selection in acquired SAA. Methods We conducted a multicenter study based on a registered database of 392 patients with SAA treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT) between 2006 and 2018. In total, 223 patients received grafts from father donors, 47 from mother donors, 91 from siblings, 29 from children, and 2 from collateral donors. Results Of the 381 patients who survived more than 28 days, 379 (99.5%) recipients were engrafted. The 2-year overall survival (OS) was 86.6 ± 2.5%, 87.1 ± 4.9%, 84.3 ± 3.9%, and 92.2 ± 5.1% for recipients of father, mother, sibling, and child grafts, respectively, ( P = 0.706). The 2-year failure-free survival (FFS) was 82.8 ± 2.7%, 86.7 ± 5.1%, 80.8 ± 4.2%, and 92.5 ± 5.1% for recipients of father, mother, sibling, and child grafts, respectively, ( P = 0.508). There was no difference in the incidence of either acute or chronic graft-versus-host disease (GVHD) among the different donor sources in multivariate analyses. There were also no differences in the OS or FFS among the different donor sources in the Cox regression analysis. However, OS was significantly better in the patients with a shorter history of aplastic anemia (< 12 months), better performance status (ECOG scores 0–1), or moderate graft mononuclear cell (MNC) counts (6–10 × 10 8 /kg), and in female recipients with male donors. The FFS was also higher in patients with a shorter history of aplastic anemia (< 12 months) and better performance status (ECOG scores 0–1). Conclusions Fathers, mothers, siblings, and children are all suitable haploidentical donors for patients with SAA.