[Efficacy of venetoclax combined azacitidine in newly diagnosed acute myeloid leukemia unfit for standard chemotherapy: a single center experience].

Objective: To investigate the effectiveness and safety of the VA regimen, which combines venetoclax with azacitidine in the treatment of patients with newly diagnosed acute myeloid leukemia (AML) who are not suitable candidates for conventional chemotherapy. Methods: In the Department of Hematology at the Second Hospital of Hebei Medical University, 66 AML patients who received venetoclax and azacitidine treatment from May 2020 to March 2022 were the subject of a retrospective study. The complete remission (CR) rate, cCR rate, ORR rate, MRD negative rate, the incidence of adverse events,1-year EFS, and OS were retrospectively analyzed. Patients subgroups with varying ages, ECOG scores, primary and secondary, risk stratifications, and gene mutation were compared for differences in efficacy and survival. Results: The median follow-up was 4.25 (0.9-19.9) months, and the median number of treatment courses was 2 (1-8) cycles. After the first cycle, the cCR rate was 78.8% , and the MRD negative rate was 51.9% . After prolonged treatment, the cCR rate was 81.8% and MRD negative rate was 66.7% . The median EFS and OS, respectively, were13.2 and 15.3 months. Secondary AML showed inferior efficacy and prognosis. IDH1/2 or NPM1 mutation groups had a significantly higher rate of CR than the control group (P<0.05) . The CR rate and MRD negative rate of patients with rebound thrombocytosis were significantly higher than those without rebound thrombocytosis (P<0.05) . Those who had epigenetic modification mutations (DNMT3, ASXL1, TET2) were more likely to benefit from ongoing therapy. The most common grade 3 and 4 adverse reactions were neutropenia, thrombocytopenia, and anemia. Conclusions: In real-world patients with newly diagnosed AML who are not candidates for standard chemotherapy, the VA regimen produces rapid deep remission. Primary AML patients, rebound thrombocytosis, IDH1/2, and NPM1 gene mutations are favorable factors for treatment benefit, and adverse reactions were tolerable.

Inhibition of p53/p21 by TWIST alleviates TNF-α induced nucleus pulposus cell senescence in vitro.

OBJECTIVE: This study aims to reveal the TWIST protein expression in the degenerated nucleus pulposus (NP), its effect on the TNF-α treated NP cells, and to explore its specific mechanism of anti-senescence. PATIENTS AND METHODS: NP tissues from spine fracture patients without intervertebral disc degeneration (IDD) and the IDD patients were collected to detect the TWIST1/2 protein expression by Western blot (WB). NP cells isolated from the healthy tissue was treated with TNF-α to induce senescence, and the TWIST1/2 protein expression was also analyzed. We transfected NP cells with the plasmid coding TWIST to upregulate its expression, which was also cultured in the TNF-α condition. Besides, the TNF-α pretreated NP cells were further stimulated with the recombinant human TWIST1/2 protein. The collagen II and senescent marker ß-galactosidase (ß-gal) were determined by immunofluorescence (IF); the MMP-13, TIMP-3, IL-10, IL-1ß mRNA expression level was detected by quantitative Real Time PCR; the cell proliferation was analyzed by CCK8 assay; the cell cycle was measured by flow cytometry. RESULTS: TWIST1/2 protein was decreased both in the degenerated NP tissue, and TNF-α treated NP cells. The overexpression of TWIST1/2 could prevent the p53, p21, ß-gal, MMP-13, and IL-1ß expression, moreover, it protected the collagen II, TIMP-3, and IL-10 expression in the TNF-α treated NP cells. Additionally, TWIST overexpression also promoted cell proliferation by ensuring the process of the cell cycle. Furthermore, the supplement of TWIST protein was functional to reverse these senescent phenotypes caused by TNF-α partly. CONCLUSIONS: TWIST alleviates the TNF-αinduced NP cells senescence via the inhibition of the p53/p21 pathway.

Rhizobial biogeography and inoculation application to soybean in four regions across China.

AIMS: The aim of the study was to survey rhizobial biogeography and to inoculate soybean with selected rhizobia in China to enhance symbiotic nitrogen fixation (SNF). METHODS AND RESULTS: Biogeography, genetic diversity and phylogeny of soybean rhizobia were surveyed. Inocula were prepared and applied to soybean. Results showed that Bradyrhizobium elkanii and Ensifer fredii were widely distributed in acid and alkaline soils respectively. Available iron was detected as the first determinant for distribution of the two rhizobia and the soybean varieties did not greatly affect the rhizobial compatibility. Geographical latitude and precipitation in June were the main geographical and climatic factors affecting the rhizobial distribution. Inoculation with selected rhizobia increased the nodule number, fresh weight, occupation ratio, seed protein content and soybean yields. CONCLUSIONS: Selection and application of effective soybean rhizobia across China according to biogeography were clarified to promote the SNF, thereby improving soybean yield. SIGNIFICANCE AND IMPACT OF THE STUDY: Rhizobial diversity and biogeography were evaluated systematically in six sites across China. Available iron and soil pH are found to be the most important determinants for the distribution of soybean rhizobia. Inoculation to soybean enhances SNF, positively correlating to the increase in soybean yield and seed protein content.

Layering Poly (lactic-co-glycolic acid)-based electrospun membranes and co-culture cell sheets for engineering temporomandibular joint disc.

The temporomandibular joint disk (TMJD) lacks blood vessels and is characterized by slow self-repair. Qualitative lesions in TMJD are difficult to repair. In this study, electrospun poly (lactic-co-glycolic acid) (PLGA) scaffolds were used to reconstruct temporomandibular joint discs by tissue engineering. Rabbit temporomandibular joint disc cells (TMJDCs) and rabbit synovium-derived mesenchymal stem cells (SMSCs) were co-cultured in 1:1 ratios. Cell sheets were induced by ascorbic acid incubated with electrospun PLGA scaffolds for 14 days in the presence (10 ng/ml in culture medium) or absence of TGF-ß3. Dimethylmethylene Blue Assay (DMMB) was used to determine the content of glycosaminoglycans in the extracellular matrix. The expression of Col1a1, Col2a1, Sox-9 and Runx-2 was quantified by RT-PCR, and the expression of type II collagen was observed by immunofluorescent staining. After 14 days of cultivation, the electrospun PLGA scaffold-loaded cell sheets could form an articular disc tissue with certain morphological characteristics. The expression of chondrogenic-related genes (Col2a1, Sox-9) and the secretion of extracellular matrix (GAG, type II collagen) in the co-culture group were close to those in the TMJDC group alone. The results suggest that PLGA electrospun scaffold-loaded co-cultured cell membrane could be used in the tissue engineering reconstruction of the temporomandibular joint disc.

Protective effect of naringenin-7-O-glucoside against oxidative stress induced by doxorubicin in H9c2 cardiomyocytes.

Doxorubicin (DOX) is one of the most effective chemotherapeutic agents, but cardiotoxicity limits its clinical use. Although the mechanisms are not entirely understood, reactive oxygen species (ROS) and cardiomyocyte apoptosis appear to be involved in DOX cardiotoxicity. Protection or alleviation of DOX cardiotoxicity can be achieved by administration of natural phenolic compounds via activating endogenous defense systems and antiapoptosis. Naringenin-7-O-glucoside (NARG), isolated from Dracocephalum rupestre Hance, could protect from cardiomyocyte apoptosis and induce endogenous antioxidant enzymes against DOX toxicity, but the effects on intracellular ROS generation and cell membrane stability were not demonstrated. In the present study, we investigated the effects of NARG on H9c2 cell morphology, viability, lactate dehydrogenase (LDH) and creatine kinase (CK) leakage, glutathine peroxidase (GSH-Px) activity, intracellular Ca2+ concentration, and ROS generation. Compared with DOX alone treatment group, the morphological injury of the cells in groups treated by DOX plus NARG was alleviated, cell viability was increased, the amount of released LDH and CK was significantly decreased, the activity of GSH-Px was increased, the content of intracellular Ca2+ and ROS generation was lowered remarkably. These results suggest that NARG could prevent cardiomyocytes from DOX-induced toxicity by their property of stabilizing the cell membrane and reducing ROS generation.

[Culture medium for protocorm differentiation in Dendrodium candidum Wall. ex Lindl].

Effects of basal culture medium, sucrose concentration, natural extracts and phytohormones on protocorm differentiation were studied. The suitable medium for protocorm differentiation has been found to be 1/2Ms basal medium plus 2% w/v sucrose, 2mg/L BA, 0.2mg/L NAA and 20% (w/v) potato extract.

[Clonal propagation of Gynostemma pentaphyllum (Thumb.) Makino in test tubes].

The explants taken from adventitious shoots or nodes of adventitious bud of Gynostemma pentaphyllum produced numerous shoots on MS medium supplemented with BA 1mg/L and IAA 0.05 mg/L. When the segments of shoots were grown on the 1/2MS medium supplemented with IBA 1 mg/L, roots were initiated differentiating to plantlets. Substitution of polyurethane sponge for agar can accelerate the growth of platlets.