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The purpose of this study in severe aplastic anemia (SAA) patients was to compare the feasibility and efficacy of haploidentical hematological stem cell transplantation combined with a single unrelated cord blood (UCB) infusion (Haplo-cord-HSCT) or haplo-identical HSCT (Haplo-HSCT) alone. The five-year graft-versus-host disease (GVHD)-free or failure-free survival (GFFS) was similar between the two groups (72.4 ± 3.4% vs. 65.4 ± 5.2%, P = 0.178); however, the five-year overall survival (OS) was more favorable in the Haplo-cord-HSCT group than that in the Haplo-HSCT group (84.0 ± 2.8% vs. 72.6 ± 4.9%, P = 0.022), as was transplantation-related mortality (16.4% vs. 27.4%, P = 0.039). Multivariate analysis showed that Haplo-cord HSCT was the only independent determinant of increased OS (P = 0.013). Explorative subgroup analysis showed that only an Human leukocyte antigen-A (HLA-A) allele match between UCB and the recipient was a beneficial factor for GFFS in the Haplo-cord-HSCT group (P = 0.011). In the haplo-cord with an HLA-A match (n = 139) or mismatch (n = 32) or Haplo-HSCT groups, a haplo-cord HLA-A allele match was associated with lower I–IV and III–IV acute GVHD. The haplo-cord with an HLA-A match subgroup also had higher five-year OS than the Haplo-HSCT group (85.4 ± 3.0% vs. 72.6 ± 4.9%, P = 0.013), and higher five-year GFFS than the Haplo-cord HLA-A allele mismatch subgroup (76.2 ± 3.6% vs. 56.3 ± 8.8%, P = 0.011). These findings suggest that the coinfusion of a single UCB potentially improves survival of Haplo-HSCT in SAA patients and that an HLA-A allele-matched UCB is the preferred option.

The protective effect of astragaloside IV (AS-IV) on myocardial injury after myocardial infarction has been reported. However, the underlying mechanism is still largely unknown. We established a myocardial infarction model in C57BL/6 mice and injected intraperitoneally with 10 mg/kg/d AS-IV for 4 weeks. The cardiac function, myocardial fibrosis, and angiogenesis were investigated by echocardiography, Masson's trichrome staining, and CD31 and smooth muscle actin staining, respectively. Cardiac mitochondrial morphology was visualized by transmission electron microscopy. Cardiac function, infarct size, vascular distribution, and mitochondrial morphology were significantly better in AS-IV-treated mice than in the myocardial infarction model mice. In vitro, a hypoxia-induced H9c2 cell model was established to observe cellular apoptosis and mitochondrial function. H9c2 cells transfected with silent information regulator 3 (Sirt3) targeting siRNA were assayed for Sirt3 expression and activity. Sirt3 silencing eliminated the beneficial effects of AS-IV and abrogated the inhibitory effect of AS-IV on mitochondrial division. These results suggest that AS-IV protects cardiomyocytes from hypoxic injury by maintaining mitochondrial homeostasis in a Sirt3-dependent manner.

BackgroundAllogeneic stem cell transplantation (allo-SCT) remains the only effective curative therapy for primary myelofibrosis. Utilization and efficacy of allo-SCT are limited by lethal complications, including engraftment failure, and acute (aGVHD) and chronic graft-versus-host disease (cGVHD). Several clinical trials have explored the use of mesenchymal stem cells (MSCs) in allo-SCT to prevent hematopoietic stem cell (HSC) engraftment failure and control GVHD.MethodsClinical data of 17 patients with primary myelofibrosis who underwent allo-SCT combined with ex vivo expanded MSC transfusion in four centers from February 2011 to December 2018 were retrospectively analyzed.ResultsAll patients received myeloablative conditioning regimen. The median number of transplanted nucleated cells (NCs) per kilogram body weight was 11.18 × 108 (range: 2.63–16.75 × 108), and the median number of CD34+ cells was 4.72 × 106 (range: 1.32–8.4 × 106). MSCs were transfused on the day of transplant or on day 7 after transplant. The median MSC infusion number was 6.5 × 106 (range: 0.011–65 × 106). None of the patients experienced primary or secondary graft failure in the study. The median time to neutrophil engraftment was 13 days (range: 11–22 days), and the median time to platelet engraftment was 21 days (range: 12–184 days). The median follow-up time was 40.3 months (range: 1.8–127.8 months). The estimated relapse-free survival (RFS) at 5 years was 79.1%, and overall survival (OS) at 5 years was 64.7%. Analysis showed that the cumulative incidence of aGVHD grade II to IV was 36% (95% CI: 8%–55%) and that of grade III to IV was 26% (95% CI: 0%–45%) at day 100. The cumulative incidence of overall cGVHD at 2 years for the entire study population was 63% (95% CI: 26%–81%). The cumulative incidence of moderate to severe cGVHD at 2 years was 17% (95% CI: 0%–42%). Seven patients died during the study, with 5 patients succumbing from non‐relapse causes and 2 from disease relapse.ConclusionThe findings of the study indicate that allo-SCT combined with MSC transfusion may represent an effective treatment option for primary myelofibrosis.

Ischemic stroke (IS) is characterized by high morbidity and high mortality. The integration of Traditional Chinese medicine (TCM) and western medicine has shown promising benefits in relieving symptoms, promoting neurological recovery, and improving the quality of life of patients with IS. In TCM, Qi-deficiency along with blood-stasis (QDBS) syndrome is one of the common types of IS that is treated by invigorating Qi and activating blood circulation. In TCM theory, improving the corresponding degree of prescription–syndrome correlation (PSC) is helpful to improve clinical efficacy. In this study, we intend to use similar prescriptions that invigorate Qi and activate blood circulation: Buyang Huanwu granules (BHG), Naoxintong capsules (NXTC), and Yangyin Tongnao granules (YTG). The goal is to evaluate their level of PSC inpatients with IS with QDBS syndrome and find relevant biomarkers to provide an objective basis for precise treatment of TCM and improve the clinical therapeutic effects. A multicenter, randomized, double-blinded, and placebo-controlled intervention trial will be conducted in IS patients with QDBS syndrome, followed by an add-on of Chinese patent medicine. A total of 160 subjects will be randomly assigned to the BHG, NXTC, YTG, and placebo groups in a 1:2:1:1 allocation ratio. All subjects will undergo 28 days of treatment and then followed for another 180 days. The primary outcome is the changes in the National Institutes of Health Stroke Scale score after 28 days of medication. The secondary outcomes include the modified Rankin scale score, activity of daily living scale score, and TCM symptom score. Data will be analyzed in accordance with a predefined statistical analysis plan. Ethical approval of this trial has been granted by the Research Ethics Committee of the First Affiliated Hospital of Zhejiang Chinese Medical University (ID: 2017-Y-004-02). Written informed consent of patients will be required. This trial is registered in the Chinese Clinical Trial Registry (ChiCTR1800015189), and the results will be disseminated to the public through peer-reviewed journals and academic conferences.

Background and Objectives: Guhong Injection (GHI) is usually administered for the treatment of stroke in clinics. Aceglutamide and hydroxyl safflower yellow A (HSYA) are its key ingredients for brain protective effect. To investigate the pharmacokinetics of aceglutamide and HSYA under pathological and normal conditions, the pharmacokinetic parameters and characteristics of middle cerebral artery occlusion (MCAO) and normal rats given the same dosage of GHI were studied compared.Methods: 12 SD rats were divided into two groups, namely, MCAO and normal groups. Both groups were treated with GHI in the same dosage. Plasma samples were collected from the jaw vein at different time points and subsequently tested by high-performance liquid chromatography (HPLC).Results: After administration of GHI, both aceglutamide and HSYA were immediately detected in the plasma. Ninety percent of aceglutamide and HSYA was eliminated within 3 h. For aceglutamide, statistically significant differences in the parameters including AUC(0−t), AUC(0−∞), AUMC(0−t), AUMC(0−∞), Cmax (P < 0.01), and Vz (P < 0.05). Meanwhile, compared with the MCAO group, in the normal group, the values of AUC(0−t), AUMC(0−t), VRT(0−t), and Cmax (P < 0.01) for HSYA were significantly higher, whereas the value of MRT(0−t) was significantly lower in the normal group.Conclusions: The in vivo trials based on the different models showed that, the pharmacokinetic behaviors and parameters of aceglutamide and HSYA in GHI were completely different. These results suggest that the pathological damage of ischemia-reperfusion has a significant impact on the pharmacokinetic traits of aceglutamide and HSYA.