Summary Data from 200 children with high‐risk acute myeloid leukaemia who underwent their first haploidentical haematopoietic stem cell transplantation (haplo‐HSCT) between 2015 and 2021 at our institution were analysed. The 4‐year overall survival (OS), event‐free survival (EFS) and cumulative incidence of relapse (CIR) were 71.9%, 62.3% and 32.4% respectively. The 100‐day cumulative incidences of grade II–IV and III–IV acute graft‐versus‐host disease (aGVHD) were 41.1% and 9.5% respectively. The 4‐year cumulative incidence of chronic GVHD (cGVHD) was 56.1%, and that of moderate‐to‐severe cGVHD was 27.3%. Minimal residual disease (MRD)‐positive (MRD+) status pre‐HSCT was significantly associated with lower survival and a higher risk of relapse. The 4‐year OS, EFS and CIR differed significantly between patients with MRD+ pre‐HSCT ( n = 97; 63.4%, 51.4% and 41.0% respectively) and those with MRD‐negative (MRD‐) pre‐HSCT ( n = 103; 80.5%, 73.3% and 23.8% respectively). Multivariate analysis also revealed that acute megakaryoblastic leukaemia without Down syndrome (non‐DS‐AMKL) was associated with extremely poor outcomes (hazard ratios and 95% CIs for OS, EFS and CIR: 3.110 (1.430–6.763), 3.145 (1.628–6.074) and 3.250 (1.529–6.910) respectively; p ‐values were 0.004, 0.001 and 0.002 respectively). Thus, haplo‐HSCT can be a therapy option for these patients, and MRD status pre‐HSCT significantly affects the outcomes. As patients with non‐DS‐AMKL have extremely poor outcomes, even with haplo‐HSCT, a combination of novel therapies is urgently needed.
Measurable residual disease (MRD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an independent risk factor for relapse in patients with acute lymphoblastic leukemia (ALL). This study aimed to assess the efficacy, safety, and immune reconstitution of chimeric antigen receptor T-cell (CAR-T) therapy in patients with molecular relapse after allo-HSCT. Eleven patients with molecular relapse of B-cell-ALL who underwent CAR-T therapy after allo-HSCT were enrolled. The rate of MRD negativity after a month of CAR-T infusion was 81.8%. Patients who bridged to second-HSCT after CAR-T therapy (
Sheep bones are a rich resource in China, but their deep processing is limited by outdated technology. Sausages are popular among various consumer groups due to their unique flavor. The purpose of this study was to optimize the preparation process of fermented-enzymatic sheep bone powder and develop calcium-fortified functional sausages with an excellent flavor, aroma, and taste. In this experiment, the fermented-enzymatic sheep bone powder was prepared by optimizing the two-bacterial fermentation process of Lactobacillus Plantarum BNCC336421 and Pediococcus Pentosaceus BNCC193259. The nutritional indexes and micro-structure were analyzed. Additionally, different ratios of fermented sheep bone powder were added into the sausages to investigate their effects on the nutritional indexes, physicochemical properties, and organoleptic quality of the sausages. The results showed that the optimal process conditions for the fermented sheep bone sludge were as follows: a strain inoculation of 3%; a compounding ratio of 1:1; a bone sludge concentration of 1:20; and fermentation time of 24 h. Under these conditions, the Ca2+ content and protein hydrolysis degree of the sheep bone were 2441.31 mg/100 mL and 23.78%, respectively. The fermented sheep bone powder analyzed using SEM, and the particle size analysis showed it was loose and porous with a small particle size. The addition of fermented sheep bone powder to the sausage increased its amino acid and calcium ion contents, improved the texture indexes such as cohesion, and enhanced both the L* value and sensory scores. The best result was observed in the 1% group (p < 0.05). It serves as a data source for developing fermented sheep bone powder and its application in sausage, offering a fresh idea and approach to achieving the high-value utilization of sheep bone.
Abstract Background Huangdi Anxiao (HDAX) is mainly used to treat diabetes and its complications for many years and has a remarkable curative effect. However, the improvement effect of HDAX in the diabetic cognitive dysfunction (DCD) model and the related mechanism is not clear. This study was aimed to explore the neuroprotective effects of HDAX and its possible mechanisms in DCD. Methods A DCD cell model was established by high glucose-induced PC12 cells, and the effect of HDAX on the cell viability was examined by MTT. Additionally, the expression of relevant genes and proteins in the apoptosis pathway of endoplasmic reticulum (ER) stress was detected. Results The results showed that HDAX increased cell viability, reduced GRP78, CHOP, Bax, procaspase-12, procaspase-9, procaspase-3 mRNA levels and GRP78, CHOP, Bax, Caspase-12, Caspase-9, Caspase-3 protein expressions, and decreased Bcl-2 mRNA level and protein expression. Conclusions These results suggested that HDAX had neuroprotective effects in the DCD cell model, which may be associated with the inhibition of the apoptosis pathway of ER stress.
Background The presence of minimal residual disease (MRD) is an independent risk factor for poor prognosis in patients with acute lymphoblastic leukemia (ALL). Moreover, the role of chimeric antigen receptor T-cell (CAR-T) therapy in patients with MRD is currently unclear. Methods We conducted a prospective study to investigate the role of CAR-T therapy in patients with persistent/recurrent MRD-positive ALL in first remission. Results A total of 77 patients who had persistent/recurrent MRD were included. Of these patients, 43 were enrolled in the CAR-T group, 20 received chemotherapy as a bridge to allogeneic hematopoietic cell transplantation (allo-HSCT), and 14 patients received intensified chemotherapy. MRD negativity was achieved in 90.7% of the patients after CAR-T infusion. Patients who received CAR-T therapy had a higher 3-year leukemia-free survival (LFS) than patients who did not (77.8% vs. 51.1%, P = 0.033). Furthermore, patients in the CAR-T group had a higher 3-year LFS than those in the chemotherapy bridge-to-allo-HSCT group [77.8% (95% CI, 64.8–90.7%) vs. 68.7% (95% CI, 47.7–89.6%), P = 0.575] and had a significantly higher 3-year LFS than those in the intensified chemotherapy group [77.8% (95% CI, 64.8–90.7%) vs. 28.6% (95% CI, 4.9–52.3%), P = 0.001]. Among the patients who received CAR-T therapy, eight were not bridged to allo-HSCT, and six (75%) remained in remission with a median follow-up of 23.0 months after CAR-T infusion. Conclusions Our findings show that CAR-T therapy can effectively eliminate MRD and improve survival in patients with a suboptimal MRD response.
Sheep bones, as the main byproduct after sheep slaughter, are rich in proteins, but their utilization in deep processing is relatively low. Currently, calcium deficiency is a common health issue that can lead to metabolic bone diseases. Peptide calcium chelate is considered a superior substance, having a significant effect on improving the absorption and utilization efficiency of calcium in the human body. This study used sheep bone byproducts as the raw material to prepare sheep bone peptide-chelated calcium (SBP-Ca) and its structure was characterized and analyzed in depth. SBP-Ca was supplemented in a low-calcium diet to assess its effects on calcium absorption and bone formation in a rat model experiencing calcium deficiency. The results showed that under optimal preparation conditions for SBP-Ca (peptide-calcium ratio set at 1 : 1, pH maintained at 7, temperature set to 45°C, and duration of 60 min), calcium could chelate with sheep bone peptide (SBP) at the sites C=O, -NH2, and -COOH sites, forming a structurally dense SBP-Ca with a chelation rate of up to 89.24%. In rats fed a low-calcium diet, SBP-Ca significantly improved the rat femoral diameter, dry weight, trabecular bone structure, bone density, and bone volume fraction ( ). A decline in serum alkaline phosphatase levels ( ), elevation in bone calcium content, and a rise in serum osteocalcin levels ( ) were observed. Furthermore, morphological studies on bone tissue suggest that SBP-Ca has the ability to restore trabecular bone structure. In conclusion, SBP-Ca has been successfully prepared as a novel calcium absorption promoter. By improving the bioavailability of calcium, bone formation was facilitated, demonstrating a significant application value in the prevention of calcium deficiency disorders.
To isolate a novel peptide with calcium-binding capacity, sheep bone protein was hydrolyzed sequentially using a dual-enzyme system (alcalase treatment following neutrase treatment) and investigated for its characteristics, separation, purification, and structure. The sheep bone protein hydrolysate (SBPH) was enriched in key amino acids such as Gly, Arg, Pro, Leu, Lys, Glu, Val, and Asp. The fluorescence spectra, circular dichroism spectra, and Fourier-transform infrared spectroscopy results showed that adding calcium ions decreased the α-helix and β-sheet content but significantly increased the random and β-turn content (p < 0.05). Carboxyl oxygen and amino nitrogen atoms of SBPH may participate in peptide–calcium binding. Scanning electron microscopy and energy dispersive spectrometry results showed that SBPH had strong calcium-chelating ability and that the peptide–calcium complex (SBPH–Ca) combined with calcium to form a spherical cluster structure. SBPH was separated and purified gradually by ultrafiltration, gel filtration chromatography, and reversed-phase high-performance liquid chromatography. Liquid chromatography-electrospray ionization/mass spectrometry identified the amino acid sequences as GPSGLPGERG (925.46 Da) and GAPGKDGVRG (912.48 Da), with calcium-binding capacities of 89.76 ± 0.19% and 88.26 ± 0.25%, respectively. The results of this study provide a scientific basis for the preparation of a new type of calcium supplement and high-value utilization of sheep bone.
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