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Background: Azacitidine is commonly used in the treatment of relapsed acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), but the effectiveness of this monotherapy is still very low. A possible mechanism of resistance to hypomethylating agents (HMAs) is the upregulation of the expression of inhibitory checkpoint receptors and their ligands, making the combination of HMAs and immune checkpoint blockade therapy a rational approach. Although the safety of anti-programmed cell death protein (PD)-1 antibodies for patients with post-allo-HSCT remains a complicated issue, the preliminary clinical result of combining azacitidine with anti-PD-1 antibodies is encouraging; however, the safety and efficacy of this approach need further investigation.Case Presentation: We reported a case of treated secondary (ts)-AML in a patient who received tislelizumab (an anti-PD-1 antibody) in combination with azacitidine. The patient relapsed after allo-HSCT and was previously exposed to HMAs-based therapy. The patient received tislelizumab for compassionate use. After the combination treatment, the patient achieved complete remission with incomplete hematologic recovery, negative minimal residual disease (MRD) by flow cytometry (FCM), and negative Wilms' tumor protein 1 (WT1). However, the patient successively developed serious immune-related adverse events (irAEs) and graft vs. host disease (GVHD) and eventually died from complications of GVHD.Conclusion: To our knowledge, this is the first case to report the combined use of tislelizumab and azacitidine to treat relapsed AML posttransplantation. This report highlights the safety concerns of using an anti-PD-1 antibody in combination with azacitidine after allo-HSCT, especially the risk of GVHD, and provides a basis for future studies.

The human umbilical cord (UC) is usually discarded as biological waste. However, it has attracted interest as a source of cells including endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs), which have demonstrated enormous potential in regenerative medicine. The present study describes a convenient protocol that has been developed to sequentially extract these two cell types from a single UC. EPCs which had properties of progenitor cells were successfully isolated from the UC vein. These cells had cobble-shaped morphology and expressed Flt-1, KDR, VE-cadherin, von Willebrand factor and CD31 mRNA, in addition to CD73, CD105 and vascular endothelial growth factor receptor-2. In addition to absorbing fluorescent-labeled acetylated low density protein and binding to fluorescein isothiocyanate-UEA-l, they were able to form vascular tube-like structures on Matrigel. Typical fibroblast-like cells, which were isolated from the Wharton's jelly, were confirmed to be MSCs by their expression of CD73, CD90 and CD105, and their ability to differentiate into adipocytes and osteoblasts. Thus, the human UC-derived cells may be suitable for use in tissue engineering and cell therapy. [ABSTRACT FROM AUTHOR]

Objective To investigate the bone mineral density of 9103 subjects who received physical examination, and to explore the epidemiology of osteoporosis (OP) in Beijing. Methods BMD of the distal one-third of the radius and the ulna of non-dominant forearm in 9103 Han subjects, who received [physical examination in our hospital from March 2012 to July 2012, was detected using DXA (ExA-3000, Osteosys Co., South Korea). The information of all the subjects, including BMD, height, weight, and BMI, were collected and recorded. The results were grouped in a 10-year range. And BMD, T-score, Z-score, incidence, and related influencing factors in each group were analyzed. Results The peak bone mass in males (0.528 ± 0.072) and females (0.451 ± 0.067) in Beijing appeared in 30-39 years old group. Along with the increase of age, BMD in each group decreased. while the incidence of OP increased. BMD in males and females younger than 30 years old was 0.47 ±0.107 and 0.436 ±0.060, respectively. And the incidence of OP in males and females was 21. 88% and 1.33%, respectively. BMD in males and females in 30-39 years old group was 0-528 ±0.072 and 0.451 ±0.067, respectively. And the incidence of OP in males and females was 7.31% and 1.71%, respectively. BMD in males and females in 40-49 years old group was 0.52 ±0.071 and 0.445 ± 0.065, respectively. And the incidence of OP in males and females was 9.88% and 2.3%, respectively. BMD in males and females in 50 - 59 years old group was 0.49 ± 0.076 and 0.396 ± 0.082, respectively. And the incidence of OP in males and females was 20.83% and 18.94%, respectively. BMD in males and females in 60-69 years old group was 0.463 ±0.085 and 0.328 ±0.071, respectively. And the incidence of OP in males and females was 35.49% and 52. 21%, respectively. BMD in males and females in 70-79 years old group was 0.416 ± 0.086 and 0.268 ± 0.072, respectively. And the incidence of OP in males and females was 57.31% and 77.59%, respectively. BMD in males and females over 80 years old was 0.384 ± 0.091 and 0.222 ±0.059, respectively. And the incidence of OP in males and females was 71. 37% and 95. 24%, respectively. The incidence of OP in people with lower BMI was significantly higher than that in people with normal BMI or higher BMI (P < 0.05). Conclusion After the peak bone mass, BMD decreases along with the increase of age and the incidence of OP increases obviously. Meanwhile, the bone mass of postmenopause women decreases obviously, and the incidence of OP is significantly higher than that in men with the same age. It is noteworthy that BMD of young men under 30 years old is not ideal, which may be related to busy work, stressful life, lack for exercise, and unhealthy lifestyle. Measurement of BMD should become the general project in medical examination, which may benefit to the early discovery and active intervention. Meanwhile, we should strengthen the health education in young people, advocate healthy lifestyle, and increase peak bone mass. All may have great significance in preventing osteoporosis. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of raloxifene HCL (RLX) on serum biochemistry, bone markers, and bone mineral density (BMD) in women with postmenopausal osteoporosis. Methods A total of 90 patients with postmenopausal osteoporosis, who were hospitalized in our department from January 2010 to January 2010, were selected. All the patients took 600 mg calcium and 0.5 μg active vitamin D every day as the basic supplements. The patients also took 60 mg RLX every week for 12 months. The obvervational indexes included BMD of the lumbar vertebrae and the hip, bone markers, and serum biochemical indexes. BMD was detected using dual-energy X-ray absorptiometry. Bone markers were determined using enzyme-linked immunosorbent method. Serum biochemical indexes were detected using enzymic method. Results BMD of the lumbar vertebrae and the Ward's triangle was 0.848 ±0.167 and 0.536 ± 0.126, respectively, which was higher than that before the treatment (0.842 ± 0.181 and 0.500 ± 0.112, respectively), and the difference was statistically significant (P < 0.05). The serum levels of CTX and BGP decreased significantly than those before the treatment, while the serum PTH level was higher than that before the treatment. No significant difference of the serum levels of blood lipids between two groups was observed. Conclusion Raloxifene hydrochloride increases BMD of the lumbar vertebrae and the hip in women with postmenopausal osteoporosis, and reduces the bone turnover significantly. So, it has good therapeutic effect for postmenopausal osteoporosis. [ABSTRACT FROM AUTHOR]

Introduction: Mesenchymal stromal cells (MSCs) have been extensively studied as a potential treatment for steroid refractory acute graft-versus-host disease (aGVHD). However, the majority of clinical trials have focused on bone marrow-derived MSCs., Methods: In this study, we report the outcomes of 86 patients with grade III-IV (82.6% grade IV) steroid refractory aGVHD who were treated with human umbilical cord-derived mesenchymal stromal cells (UC-MSCs). The patient cohort included 17 children and 69 adults. All patients received intravenous infusions of UC-MSCs at a dose of 1 × 106 cells per kg body weight, with a median of 4 infusions (ranging from 1 to 16)., Results: The median time between the onset of aGVHD and the first infusion of UC-MSCs was 7 days (ranging from 3 to 88 days). At day 28, the overall response (OR) rate was 52.3%. Specifically, 24 patients (27.9%) achieved complete remission, while 21 (24.4%) exhibited partial remission. The estimated survival probability at 100 days was 43.7%. Following a median follow-up of 108 months (ranging from 61 to 159 months), the survival rate was approximately 11.6% (10/86). Patients who developed acute lower GI tract and liver GVHD exhibited poorer OR rates at day 28 compared to those with only acute lower GI tract GVHD (22.2% vs. 58.8%; p= 0.049). No patient experienced serious adverse events., Discussion: These finding suggest that UC-MSCs are safe and effective in both children and adults with steroid refractory aGVHD. UC-MSCs could be considered as a feasible treatment option for this challenging conditon. (NCT01754454)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Niu, Li, Xu, Sheng, Tian, Ning, Hu, Chen, Li, Wang, Lou, Liu, Su, Sun, Qiao, Wang, Zhang, Lan, Xie, Ren, Peng, Wang, Shi, Zhao, Zhang, Chen, Zhang and Hu.)

We have witnessed the fast progress of cathodic photoelectrochemistry over the past decades, though its signal transduction tactic still lacks diversity. Exploring new sensing strategies for cathodic photoelectrochemistry is extremely demanding yet hugely challenging. This article puts forward a unique idea to incorporate an enzymatic reaction-invoked surface polarization effect (SPE) on the surface of BiOIO 3 to implement an innovative cathodic photoelectrochemical (PEC) bioanalysis. Specifically, the thioredoxin reductase (TrxR)-mediated reaction produced the polar glutathione (GSH), which spontaneously coordinated to the surface of BiOIO 3 and induced SPE by forming a polarized electric field, resulting in improved electron (e - ) and hole (h + ) pair separation efficiency and an enhanced photocurrent output. Correlating this phenomenon with the detection of TrxR exhibited a high performance in terms of sensitivity and selectivity, achieving a linear range of 0.007-0.5 μM and a low detection limit of 2.0 nM (S/N = 3). This study brings refreshing inspiration for the cathodic PEC signal transduction tactic through enzyme-mediated in situ reaction to introduce SPE, which enriches the diversity of available signaling molecules. Moreover, this study unveils the potential of in situ generated SPE for extended and futuristic applications.

Objective: To investigate the efficacy of allogeneic hematopoietic stem cell transplantation（allo-HSCT）in the treatment of patients with Ⅲ,Ⅳ non-Hodgkin lymphoma（NHL）, and compared the efficacy between Cy- fractionated to talbody irradiation（fTBI）based conditioning regimen and Maryland, horse flange and mitoxantrone（BMM）., Methods: The clinical data of 47 patients with Ⅲ, Ⅳ NHL after allo- HSCT from November 1998 to May 2014 were collected and retrospectively analyzed. To observe the hematopoietic reconstruction recovery after transplantation, cumulative incidence of acute graft- versus- host- disease （aGVHD） and chronic graft- versus- host- disease （cGVHD）, transplantation related mortality （TRM）, recurrence rate （RR）, disease- free survival （DFS）, overall survival（OS）. Compare the efficacy of fTBI and BMM conditioning regimen at the same time., Results: Neutrophils achieving 0.5×10⁹/L and platelets achieving 50×10⁹/L on day 17 （range, 10- 72） post transplantation. Acute GVHD occurred in 53.19%, among them, grade Ⅰ-Ⅱ occurred in 42.55%, grade Ⅲ-Ⅳ occurred in 10.65%, and cGVHD occurred in 21.28%. 21 patients were alive with a median follow up of 9.7 months（0.2-149.1 months）. Overall survival（OS）was 73.5%, 49.3%, 40.1% respectively in the first, third and fifth year in Cy-fTBI group; in BMM group it was 67.8%, 32.9% and 31.4% respectively, and disease-free survival（DFS）was 65.3%, 45.6%, 30.2% respectively in the first, third and fifth year. In Cy-fTBI group, the recurrence rate（RR）and transplantation related mortality（TRM）in the first year were 18.9%, 23.0% respectively, the third year were 19.5%, 38.3% and the fifth year were 35.2%, 39.2%. In BMM group, RR and TRM in the first year were 27.4%, 24.5% respectively, the third year were 38.9%, 46.4% and the fifth year were 39.2%, 48.2%. However, there was no significant difference in the indicator of OS, DFS, RR, TRM in the two groups., Conclusion: Allo-HSCT could make some Ⅲ,Ⅳ NHL patients achieve long-term disease- free survival, but the TRM was still high relatively. Moreover, compared with the program of BMM conditioning regimen, Cy-fTBI might reduce the TRM and RR, meanwhile, increase the DFS and OS. However, due to the small number cases of two groups, there was no statistical significant difference.