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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.

The application of haploidentical hematopoietic stem cell transplantation (HSCT) with mesenchymal stem cell (MSC) infusion as a treatment regimen for severe aplastic anemia (SAA) has been reported to be efficacious in single-arm trials. However, it is difficult to assess without comparing the results with those from a first-line, matched-sibling HSCT. Herein, we retrospectively reviewed 91 patients with acquired SAA. They received HSCT from haploidentical donors combined with MSC transfer (HID group). We compared these patients with 103 others who received first-line matched-sibling HSCT (MSD group) to evaluate relative treatment efficacy. Compared with the patients in the MSD group, those in the HID group presented with higher incidences of grades II–IV and III–IV acute graft versus host disease (aGvHD) and chronic graft versus host disease (cGvHD) ( p < 0.05). However, the incidence of myeloid and platelet engraftment, graft failure, poor graft function, and extensive cGvHD were comparable for both groups. The median follow-up was 36.6 months and the 3-year overall survival rate was similar for both groups (83.5% versus 79.1%). Univariate and multivariate analyses revealed that time intervals greater than 4 months from diagnosis to transplantation, experienced graft failure, poor graft function, or grade III–IV aGvHD were significantly associated with adverse outcomes. All HID patients received MSC co-transplantation with hematopoietic stem cells. However, the infused MSCs were derived from umbilical cord (UC-MSC group; 43 patients) or bone marrow (BM-MSC group; 48 patients) and were administered at different medical centers. We first compared the outcomes between the two groups and detected that the BM-MSC group exhibited lower incidences of grade III–IV aGvHD and cGvHD ( p < 0.05). This study suggests that co-transplantation of hematopoietic and MSCs significantly reduces the risk and incidence of graft rejection and may effectively improve overall survival in patients with SAA even in the absence of closely related histocompatible donor material.

Chinese medicine comprehensive therapy is an effective treatment for the middle/late stage patients of PHC, and it could extend the PRST, improve the patients' QOL and long-term survival with less adverse reaction.

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This study investigated the correlation between elevated serum uric acid (SUA) and angiotensinogen in obesity patients with hypertension. A total of 162 obese and 162 nonobese men with hypertension were recruited in this study. Plasma angiotensinogen levels were measured by enzyme-linked immunosorbent assay. Fasting insulin (FINS) was evaluated by radioimmunoassay. Compared with nonobese patients, obese patients exhibited higher levels of angiotensinogen, FINS, and homeostasis model assessment index-insulin resistance (HOMA-IR) (P<.001 for all). Moreover, these indexes significantly increased in obese patients in the highest tertile of SUA when compared with those in the lowest tertile of SUA (P<.001, P=.002, P=.007, respectively). In the obese group, SUA levels were significantly related to angiotensinogen, FINS, and HOMA-IR, respectively. Furthermore, it was demonstrated that obesity 9 uric acid was an independent contributor to angiotensinogen (b=0.257, P<.001). In conclusion, elevated SUA is strongly related to angiotensinogen in an obesity-dependent manner in hypertension. J Clin Hypertens (Greenwich). 2014;16:569-574. ª 2014 Wiley Periodicals, Inc.Obesity, with increasing worldwide prevalence in the population, not only causes severe harm to individual health but also imposes a considerable burden on our healthcare system. Obesity is one of the most important risk factors for the development of hypertension. Data from the Framingham Heart Study have demonstrated that approximately 78% of the male hypertensive population and 65% of the female hypertensive population can be directly linked to obesity.1 The pathophysiology of obesity-related hypertension is very complex, yet has been elucidated. Several mechanisms appear to be implicated in it, including renin-angiotensin-aldosterone system activation, increased sympathetic nervous system activity, dysregulated adipokines secretion, insulin resistance, endothelial dysfunction. 2Hyperuricemia commonly occurs in patients at high risk for cardiovascular diseases, 3 especially overweight and obese hypertensive patients. 4 Recently, epidemiological surveys have shown a strong association between uric acid (UA) and the occurrence and development of hypertension, 5 and it was further confirmed by a prospective study conducted in Japanese. 6 Moreover, it was reported that lowering UA with allopurinol resulted in blood pressure (BP) reduction in adolescents with newly diagnosed hypertension and patients with the metabolic syndrome. 7,8 Data have established that UA is also causally implicated in hypertension in animal models with hyperuricemia induced by oxonic acid or a high fructose diet.9,10 Renin-angiotensin system (RAS) activation is one of the most important mechanisms for the pathophysiological link between increased UA levels and hypertension. 11 However, little is known about the relationship between serum UA (SUA) and plasma angiotensinogen in obese hypertensive patients.Adipose tissue contains all components of the systemic RAS.12 Adipose-derived angiote...