Cord-Blood Engraftment Using an Enhanced Dual-Conditioning Regimen for Malignant Hematologic Diseases.

To explore a more effective conditioning regimen for umbilical cord blood transplantation (UCBT) to treat hematologic malignancies, we conducted a cohort study of a fludarabine/busulfan/cytarabine plus cyclophosphamide 200 mg/kg regimen. Forty-two consecutive patients with leukemia, myelodysplastic syndrome, or lymphoma received the regimen. The median number of infused total nucleated cells per kilogram was 5.5 × 107 (1.81-20.6), the median number of infused CD34+ cells per kilogram was 1.58 × 105 (0.58-6.6), and the median follow-up for surviving patients was 37 months (4.0-79.5 months). The cumulative incidence of neutrophil engraftment at 31 days was 100% [95% confidence interval (CI): 0.9159-1.0], and the median time to neutrophil engraftment was 19 days. The cumulative incidence of nonrelapse mortality was 12.76% (95% CI: 0.0455-0.2356) at 180 days and 3 years. The 3-year overall survival (OS) and disease-free survival (DFS) rates were 71.6% and 59.6%, respectively. Especially in patients who received transplants in the early and intermediate stages, the 3-year OS and DFS rates were 90.3% (95% CI: 0.805-1.0) and 76.2% (95% CI: 0.608-0.956), respectively. The regimen significantly improved engraftment and survival, indicating that the high graft failure of UCBT was caused by rejection.

Identifying patients with major depressive disorder based on tryptophan hydroxylase-2 methylation using machine learning algorithms.

OBJECTIVES: This study aimed to identify patients with major depressive disorder (MDD) by developing different machine learning (ML) models based on tryptophan hydroxylase-2 (TPH2) methylation and environmental stress. METHODS: The data were collected from 291 patients with MDD and 100 healthy control participants: individual basic information, the Negative Life Events Scale (NLES) scores, the Childhood Trauma Questionnaire (CTQ) scores and the methylation level at 38 CpG sites in TPH2. Information gain was used to select critical input variables. Support vector machine (SVM), back propagation neural network (BPNN) and random forest (RF) algorithms were used to build recognition models, which were evaluated by the 10-fold cross-validation. SHapley Additive exPlanations (SHAP) method was used to evaluate features importance. RESULTS: Gender, NLES scores, CTQ scores and 13 CpG sites in TPH2 gene were considered as predictors in the models. Three ML algorithms showed satisfactory performance in predicting MDD and the BPNN model indicated best prediction effects. CONCLUSION: ML models with TPH2 methylation and environmental stress were identified to possess great performance in identifying patients with MDD, which provided precious experience for artificial intelligence to assist traditional diagnostic methods in the future.

circAMOTL1L Suppresses Renal Cell Carcinoma Growth by Modulating the miR-92a-2-5p/KLLN Pathway.

Accumulating evidence indicates that the dysregulation of circular RNAs (circRNAs) contributes to tumor progression; however, the regulatory functions of circRNAs in renal cell carcinoma (RCC) remain largely unknown. In this study, the function and underlying mechanism of circAMOTL1L in RCC progression were explored. qRT-PCR showed the downregulation of circAMOTL1L in RCC tissues and cell lines. The decrease in circAMOTL1L expression correlated with the tumor stage, metastasis, and poor prognosis in patients with RCC. Functional experiments revealed that circAMOTL1L inhibited cell proliferation and increased apoptosis in RCC cells. Subcutaneous implantation with circAMOTL1L-overexpressing cells in nude mice decreased the growth ability of the xenograft tumors. Mechanistically, circAMOTL1L served as a sponge for miR-92a-2-5p in upregulating KLLN (killin, p53-regulated DNA replication inhibitor) expression validated by bioinformatics analysis, oligo pull-down, and luciferase assays. Further, reinforcing the circAMOTL1L-miR-92a-2-5p-KLLN axis greatly reduced the growth of RCC in vivo. Conclusively, our findings demonstrate that circAMOTL1L has an antioncogenic role in RCC growth by modulating the miR-92a-2-5p-KLLN pathway. Thus, targeting the novel circAMOTL1L-miR-92a-2-5p-KLLN regulatory axis might provide a therapeutic strategy for RCC.

Effect of Qizhitongluo capsule on lower limb rehabilitation after stroke: A randomized clinical trial.

BACKGROUND: An individual's level of lower limb motor function is associated with his or her disability level after stroke, and motor improvement may lead to a better prognosis and quality of life. Data from animal models show that Qizhitongluo (QZTL) capsule facilitates recovery after focal brain injury. We aimed to validate the efficacy and safety of the QZTL capsule for promoting lower limb motor recovery in poststroke patients. METHODS: In this randomized, multicenter, double-blind, placebo- and active-controlled trial from 13 sites in China, participants with ischemic stroke and Fugl-Meyer motor scale (FMMS) scores of <95 were eligible for inclusion. Patients were randomly assigned in a 2:1:1 ratio to the QZTL group, Naoxintong (NXT) group or placebo group for 12 weeks at 15-28 days after the onset of stroke. The primary outcome was the change in the Lower Limb FMMS (FMMS-LL) score from baseline over the 12-week intervention period. RESULTS: 622 participants were randomly assigned to the QZTL group (309), NXT group (159), or placebo group (154). The FMMS-LL score increased by 4.81 points (95 % CI, 4.27-5.35) in the QZTL group, by 3.77 points (95 % CI, 3.03-4.51) in the NXT group and by 3.00 points (95 % CI, 3.03-4.51) in the placebo group at week 12. The QZTL group showed significantly larger improvements compared with the placebo group at each interview from weeks 4-12 (difference, 0.89 [0.30,1.49] at week 4, P = 0.0032; difference, 1.83[1.01,2.66] at 90 days poststroke, P < 0.0001; difference, 1.81[0.88,2.74] at week 12, P = 0.0001). CONCLUSION: The QZTL capsule is an effective treatment for lower limb motor impairment. The finding indicates that the QZTL capsule may be used as a potential new strategy for stroke rehabilitation.

Viscoelastic Mechanical Responses of HMAP under Moving Load.

In order to represent the mechanical response laws of high-modulus asphalt pavement (HMAP) faithfully and objectively, the viscoelasticity of high-modulus asphalt mixture (HMAM) was considered, and the viscoelastic mechanical responses were calculated systematically based on moving load by numerical simulations. The performances of the HMAP in resistance to the deformation and the cracking at the bottom layer were compared with the ordinary asphalt pavement. Firstly, Lubao and Honeywell 7686 (H7686) were selected as the high modulus modifiers. The laboratory investigations of Asphalt mix-70 penetration, Asphalt mix-SBS (styrene-butadiene-styrene), HMAM-Lubao and HMAM-H7686 were carried out by dynamic modulus tests and wheel tracking tests. The conventional performances related to the purpose of using the HMAM were indicated. The master curves of the storage moduli were obtained and the viscoelastic parameters were fitted based on viscoelastic theories. Secondly, 3D pavement models based on moving loads for the viscoelastic structures were built using the non-linear finite element software ABAQUS. The wheel path was discretized in time and space to apply the Haversine wave load, and then the mechanical responses of four kinds of asphalt pavement were calculated. Finally, the sensitivity analysis was carried out. The results showed that the addition of the high modulus modifiers can improve the resistance to high-temperature rutting of the pavements. Except for the tensile strain and stress at the bottom of the underlayer, other responses decreased with the increases of the dynamic moduli and the change laws of the tensile strain and stress were affected by the range of the dynamic modulus. The tensile stress at the bottom of the asphalt layer would be too large if the modulus of the layer were too large, and a larger tensile strain would result. Therefore, the range of the modulus must be restricted to avoid the cracking due to excessive tension when using the HMAM. The resistance of the HMAP to deformation was better and the HMAP was less sensitive to load changes and could better withstand the adverse effects inflicted by heavy loads.