This study aimed to evaluate the efficacy and safety of daratumumab as a maintenance treatment after autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with newly diagnosed ...multiple myeloma (NDMM) .
The clinical data, hematological and renal response, and safety of 15 post-transplant patients with NDMM who had received daratumumab maintenance between May 1, 2022 and June 30, 2023 were retrospectively analyzed.
Fifteen patients (11 males and 4 females) with a median age of 58 (41-72) years were included. Thirteen patients did not receive daratumumab during induction therapy and auto-HSCT, 6 patients had renal impairment, and nine patients had high-risk cytogenetics. The median infusion of daratumumab was 12 (6-17) times, and the median duration of maintenance was 6 (1.5-12) months. The treatment efficacy was evaluated in all 15 patients, and daratumumab maintenance therapy increased the rate of stringent complete response from 40% to 60%. The renal response rate and median estimated glo
In this paper, Cu40Zr44Ag8Al8 bulk metallic glass composites (BMGCs) consisting of various volume fraction of nanocrystals embedded in the amorphous matrix was synthesized by controlled annealing ...treatment of an as-cast BMGCs. The high temperature compression behaviors of the BMGCs were characterized in the supercooled liquid region. Results show that the flow stresses keep increasing after an initial decrease with extension of the annealing time. With annealing the values of activation volume Vact is determined to be increasing from 283.6216Ǻ3 to 305.553Ǻ3, suggesting that the jump of atoms is a cooperative process during the high-temperature deformation. Flow behavior of the BMGCs annealed for less than 8min transform from Newtonian to non-Newtonian dependant on the stain rate and can be successively fitted by the visco-plasticity model. Fitting results indicate that deformation behaviors of these samples are governed by homogeneous flow of the amorphous matrix and indeed determined by the viscosities in the Newtonian flow stage. However, the BMGCs annealed for 8min exhibit a non-Newtonian flow over the entire compression process and fail to be fitted by the visco-plasticity model. Micrographs of the sample reflect an impinged structure, indicating that high temperature deformation behavior of the BMGCs with high volume fractions of particles is indeed controlled by that of a backbone of particles.
Exercise improves insulin sensitivity and oxidative capacity in skeletal muscles. However, the effect of exercise on substrate oxidation is less clear in obese and type 2 diabetic subjects than in ...lean subjects. We investigated glucose and lipid metabolism and gene expression after 48 h with low-frequency electrical pulse stimulation (EPS), as an in vitro model of exercise, in cultured myotubes established from lean nondiabetic subjects and severely obese subjects (BMI ≥ 40 kg/m(2)) with and without type 2 diabetes. EPS induced an increase in insulin sensitivity but did not improve lipid oxidation in myotubes from severely obese subjects. Thus, EPS-induced increases in insulin sensitivity and lipid oxidation were positively and negatively correlated to BMI of the subjects, respectively. EPS enhanced oxidative capacity of glucose in myotubes from all subjects. Furthermore, EPS reduced mRNA expression of slow fiber-type marker (MYH7) in myotubes from diabetic subjects; however, the protein expression of this marker was not significantly affected by EPS in either of the donor groups. On the contrary, mRNA levels of interleukin-6 (IL-6) and IL-8 were unaffected by EPS in myotubes from diabetic subjects, while IL-6 mRNA expression was increased in myotubes from nondiabetic subjects. EPS-stimulated mRNA expression levels of MYH7, IL-6, and IL-8 correlated negatively with subjects' HbA1c and/or fasting plasma glucose, suggesting an effect linked to the diabetic phenotype. Taken together, these data show that myotubes from different donor groups respond differently to EPS, suggesting that this effect may reflect the in vivo characteristics of the donor groups.
During the curing process of thermoset composites, residual stresses inevitably develop in them and lead to their curing deformation after the manufacturing process. This work was aimed at ...investigating the effect of tool–part interaction and bending stiffness on the curing deformation of L-shaped composite structures. Therefore, a twostep calculation model was developed. It consists of a numerical model to capture the residual stress due to the tool–part interaction and a viscoelastic model considering the anisotropic material properties. Calculation results were compared with experimental data, and a good agreement was found to exist between them.
A decrease in skeletal muscle lipolysis and hormone sensitive-lipase (HSL) expression has been linked to insulin resistance in obesity. The purpose of this study was to identify potential intrinsic ...defects in lipid turnover and lipolysis in myotubes established from obese and type 2 diabetic subjects. Lipid trafficking and lipolysis were measured by pulse-chase assay with radiolabeled substrates in myotubes from non-obese/non-diabetic (lean), obese/non-diabetic (obese) and obese/diabetic (T2D) subjects. Lipolytic protein content and level of Akt phosphorylation were measured by Western blot. HSL was overexpressed by adenovirus-mediated gene delivery. Myotubes established from obese and T2D subjects had lower lipolysis (−30–40%) when compared to lean, using oleic acid as precursor. Similar observations were also seen for labelled glycerol. Incorporation of oleic acid into diacylglycerol (DAG) and free fatty acid (FFA) level was lower in T2D myotubes, and acetate incorporation into FFA and complex lipids was also lower in obese and/or T2D subjects. Both protein expression of HSL (but not ATGL) and changes in DAG during lipolysis were markedly lower in cells from obese and T2D when compared to lean subjects. Insulin-stimulated glycogen synthesis (−60%) and Akt phosphorylation (−90%) were lower in myotubes from T2D, however, overexpression of HSL in T2D myotubes did not rescue the diabetic phenotype. In conclusion, intrinsic defects in lipolysis and HSL expression co-exist with reduced insulin action in myotubes from obese T2D subjects. Despite reductions in intramyocellular lipolysis and HSL expression, overexpression of HSL did not rescue defects in insulin action in skeletal myotubes from obese T2D subjects.
•Lipid/glycerol uptake and lipolysis are reduced in myotubes from obese donors without and with T2D.•HSL protein expression is markedly reduced in myotubes from obese and T2D subjects.•Defects in lipolysis and HSL expression co-exist with reduced insulin action.•Rescuing HSL expression in T2D myotubes does not rescue the diabetic phenotype.
Objective: This study investigated the efficacy and safety of denosumab (DENOS) versus zoledronic acid (ZOL) in the bone disease treatment of newly diagnosed multiple myeloma. Methods: The clinical ...data of 80 patients with myeloma bone disease (MBD) at the Fifth Medical Center of PLA General Hospital between March 1, 2021 and June 30, 2023 were retrospectively reviewed. Eighteen patients with severe renal impairment (SRI, endogenous creatinine clearance rate<30 ml/min) were treated with DENOS, and 62 non-SRI patients were divided into DENOS (30 patients) and ZOL group (32 patients) . Results: Hypocalcemia was observed in 26 (33%) patients, and 22 patients developed hypocalcemia during the first treatment course. The incidence of hypocalcemia in the non-SRI patients of DENOS group was higher than that in the ZOL group 20% (6/30) vs 13% (4/32), P=0.028. The incidence of hypocalcemia in SRI was 89% (16/18). Multivariate logistic regression analysis revealed that endogenous creatinine clearance rate<30 ml/min w
This study investigated the efficacy and feasibility of inducing the differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) into hepatocyte-like cells in vitro using Sprague Dawley ...rats, as a model of hepatocyte generation for cell transplantation. BMSCs were isolated and grown using the adherent method and exposed to 5 or 10% liver tissue homogenate, before being collected for analysis after 0, 7, 14, and 21 days. Immunofluorescence and western blotting were employed to detect the liver-specific markers a-fetoprotein (AFP) and albumin (ALB). Supernatant urea content was also measured to verify that differentiation had been induced. After 7 days in the presence of 10% liver tissue homogenate, BMSCs demonstrated hepatocyte-like morphological characteristics, and with prolonged culture time, liver-specific markers were gradually produced at levels indicating cell maturation. AFP expression peaked at 14 days then began to decrease, while both urea and ALB levels increased with induction time. Overall, marker expression in the 5% homogenate group was less than or equal to the 10% group at each time point. Thus, in a rat model, liver tissue homogenate obtained from partial hepatectomy can induce the differentiation of BMSCs into hepatocyte-like cells. This method is simple, feasible, and has remarkable real-world application potential.
The liver is the human body largest digestive and metabolic organ, and a very important immune organ. This paper discusses the location and morphology of hepatic sinusoidal endothelial cells, ...dendritic cells, hepatic stellate cells, and Kupffer cells in the liver and their role in regulating immune functions. Therefore, here we provide a preliminary understanding of the immune regulatory function of liver cells, and information on the occurrence and treatment of liver diseases.
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