Successful use of Palbociclib combined with Venetoclax and Azacitidine in an adult with refractory/relapsed therapy-related acute myeloid leukemia.

BACKGROUND: Therapy-related acute myeloid leukemia (t-AML) is considered high risk as it related to prior exposure to cytotoxic chemotherapy agents for solid tumors or hematologic malignancies. Compared with de novo AML, t-AML is associated with lower remission rates, inferior overall survival (OS) and higher relapse rates. Many efforts have been devoted to improving the overall but with limited success, and novel strategy is thus highly needed. CASE DESCRIPTION: We reported one patient with refractory/relapsed t-AML was successfully treated with Palbociclib combined with Venetoclax and Azacytidine (AZA). In this case, a 47-year-old patient with t-AML recurred during Venetoclax in combination with AZA therapy. However, the patient achieved morphological, immunophenotypic and molecular complete remission again after Palbociclib combined with Venetoclax and AZA. CONCLUSIONS: Although only one successful case is presented here, three-drug combination regimens should be considered as another treatment option for t-AML in the future.

Study on the trade-off/synergy between ecosystem services and human well-being based on land use in Weinan City, China.

Change of land use have important impacts on ecosystem services (ESs) and human well-being (HWB), yet the trade-off/synergy among land use, ESs, and HWB has still not received sufficient attention at city regional scales level. Weinan City in the southern of the Loess Plateau of China was taken as the study area. Based on ArcGIS, InVEST model, and RUSLE model, the characteristics of spatial and temporal variations of land use and ESs from 2000 to 2020 were analyzed, and the trade-off/synergy relationship between land use, ESs, and HWB was quantified using correlation analysis. The results indicated that the area of cultivated land decreased significantly and the area of built-up land increased significantly from 2000 to 2020 in Weinan City. The grain production, soil conservation, and water yield functions showed an increasing trend, which was a synergistic relationship with HWB. Carbon storage and habitat quality functions showed a decreasing trend, which was a trade-off relationship with HWB. The index value of HWB has increased significantly, mainly in the added value of agricultural and rural per capita income. Land use intensity has a trade-off relationship with GP, WY functions, and HWB. There are many factors that affect this trade-off/synergy relationship, such as land use patterns, economic development, and population growth. The study can provide a theoretical basis for the sustainable development of regional economy and nature.

Ecological risk assessment and restoration area identification of Pengyang County on the basis of the landscape pattern and function.

The joint landscape ecological risk as well as ecological corridors for ecological restoration area identification is of great significance to the past evolution and future development of landscapes. Ecological risks were assessed based on the landscape pattern and functional changes in Pengyang County in 2000, 2010, and 2020; ecological restoration areas were divided based on ecological risks and security pattern. Results showed that the ecological risk types in Pengyang County were mainly low risk from 2000 to 2010 and distributed in the central region, while the high-risk areas increased from 2010 to 2020 and were concentrated in the southern residential area. According to a comprehensive assessment of the landscape ecological risks, an ecological security pattern consisting of 17 ecological source points and 34 potential ecological corridors with an average length of 6.57 km was identified. Three ecological restoration areas were eventually identified: mining restoration areas, mountain restoration area, and urban restoration area. Our results would provide an important perspective for the sustainable development of regional natural landscape resources.

Tim-3 protects against cisplatin nephrotoxicity by inhibiting NF-κB-mediated inflammation.

The impact of Tim-3 (T cell immunoglobulin and mucin domain-containing protein 3) on cisplatin-induced acute kidney injury was investigated in this study. Cisplatin-induced Tim-3 expression in mice kidney tissues and proximal tubule-derived BUMPT cells in a time-dependent manner. Compared with wild-type mice, Tim-3 knockout mice have higher levels of serum creatinine and urea nitrogen, enhanced TUNEL staining signals, more severe 8-OHdG (8-hydroxy-2' -deoxyguanosine) accumulation, and increased cleavage of caspase 3. The purified soluble Tim-3 (sTim-3) protein was used to intervene in cisplatin-stimulated BUMPT cells by competitively binding to the Tim-3 ligand. sTim-3 obviously increased the cisplatin-induced cell apoptosis. Under cisplatin treatment conditions, Tim-3 knockout or sTim-3 promoted the expression of TNF-α (tumor necrosis factor-alpha) and IL-1ß (Interleukin-1 beta) and inhibited the expression of IL-10 (interleukin-10). NF-κB (nuclear factor kappa light chain enhancer of activated B cells) P65 inhibitor PDTC or TPCA1 lowed the increased levels of creatinine and BUN (blood urea nitrogen) in cisplatin-treated Tim-3 knockout mice serum and the increased cleavage of caspase 3 in sTim-3 and cisplatin-treated BUMPT cells. Moreover, sTim-3 enhanced mitochondrial oxidative stress in cisplatin-induced BUMPT cells, which can be mitigated by PDTC. These data indicate that Tim-3 may protect against renal injury by inhibiting NF-κB-mediated inflammation and oxidative stress.