Impressive responses have been observed in patients with cancer treated with checkpoint inhibitory anti-programmed cell death-1 (PD-1) or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibodies through disinhibiting the immune system. However, tumors possess complex immunosuppressive tumor microenvironment to present therapeutic obstacles and the response rates to immune checkpoint inhibition remain low. One significant barrier to the efficacy of anti-PD1 treatment is the recruitment of myeloid-derived suppressor cells (MDSCs) into the tumor. MDSCs dramatically increased in peripheral blood of patients with osteosarcoma and prohibited both T-cell activation and infiltration. Here we demonstrated functional inhibition of G-MDSCs with ( S )-(-)-N-[2-(3-Hydroxy-1H-indol-3-yl)-methyl]-acetamide (SNA), a specific inhibitor of PI3Kδ/γ, could prime tumor microenvironment, resultantly enhancing the therapeutic efficacy of anti-PD1 treatment in a syngeneic osteosarcoma tumor model. Combining SNA with anti-PD1 dramatically slowed osteosarcoma tumor growth and prolonged survival time of tumor-bearing mice, at least in part mediated through CD8 + T cells. Our results demonstrated that addition of SNA to anti-PD1 significantly altered infiltration and function of innate immune cells, providing the rationale for combination therapy in patients with osteosarcoma through inhibiting the function of MDSCs with a selective PI3Kδ/γ inhibitor to enhance responses to immune checkpoint blockade.
Introduction. This study aimed to compare and analyze the effect of preoperative zoledronic acid (ZOL) administration on pain intensity after percutaneous vertebroplasty (PVP) for osteoporotic vertebral compression fracture (OVCF). Methods. The study included 242 patients with OVCFs who underwent PVP in our hospital between January 2015 and June 2018. The patients were randomly assigned to either a ZOL group (n = 121) or a control group (n = 121). The patients in the ZOL group were treated preoperatively with intravenous infusion of 5 mg ZOL. Those in the control group were treated without ZOL. All the patients were followed up for 1 year. Results. No statistically significant differences in age, sex, weight, and body mass index (BMI) were found between the two groups. During the follow-up period, the visual analog scale score and Oswestry dysfunction index score in the ZOL group were lower than those in the control group. The bone mineral density at 6 or 12 months after treatment was significantly higher and the levels of the bone metabolism markers were significantly lower in the ZOL group than in the control group (P<0.05 for both). Two patients in the treatment group had new vertebral fractures, whereas 13 patients in the control group had new vertebral fractures, which translate to recompression vertebral fracture incidence rates of 1.7% and 10.7%, respectively. The incidence rate of mild adverse reactions was significantly higher in the ZOL group than in the control group, but all the cases were endurable. Conclusion. Intravenous infusion of ZOL before PVP can effectively reduce postoperative pain intensity, reduce bone loss, increase bone density, reduce the risk of refracture, and improve patient quality of life.
As a global health problem, cardiovascular disease threatens the lives of human beings. It has been reported that microRNAs (miRs) are important in regulating coronary atherosclerosis. In the present study, the expression levels of miR-370 in peripheral blood mononuclear cells of patients with coronary atherosclerosis were significantly increased compared with healthy patients, as demonstrated by reverse transcription-quantitative polymerase chain reaction analysis. Additionally, the target of miR-370 was predicted as Forkhead Box 1 (FOXO1) with bioinformatics, and was confirmed by a dual luciferase assay. The mRNA and protein expression levels of FOXO1 were inhibited by miR-370. Furthermore, the invasion and proliferation of human umbilical vein endothelial cells were promoted by miR-370 via inhibiting the expression of FOXO1. The results obtained in the present study demonstrated that miR-370 served an important role in regulating coronary atherosclerosis via targeting FOXO1. The present data also indicated that miR-370 may be a promising molecular target for treating coronary atherosclerosis.
C 19 H 22 N 3 NdO 16 ,monoclinic, P12 1 /c1(no. 14), a =11.347(2) Å, b =10.857(2) Å, c =19.514(3) Å, b =92.927(2)°, V =2400.9 Å 3 , Z =4,Rgt(F) =0.022, wR ref (F 2 ) =0.053, T =296 K. Source of materialThe mixture of Nd(NO 3)3.·.6H2O( 0.088 g, 0.2 mmol) and 4-hydroxypyridine-2,6-dicarboxylic acid (H 2CAM, 0.074 g, 0.4 mmol), was stirred into 15 ml aqueous solution. Then the pH value was adjusted to approx. 6with 1.5 Msolution of ammonia. And then 5m le thanol solution of 4-hydroxypyridine (4-Hpy, 0.025 g, 0.2 mmol) was added. The reaction mixture was heated on awater bath for 10 hat70°C, then filtered. The resulting clear solution was diffused with diethyl ether vapor at room temperature for two weeks, block-shaped pink crystals were obtained, the products are insoluble in water (yield 0.049 g, 36 %). Elemental analysis -found: C, 32.61 %; H, 3.18 %; N, 6.14 %; calculated for C 19 H 22 N 3 NdO 16 :C,32.95 %; H, 3.20 %; N, 6.06 %. IR data are available in the CIF. DiscussionThe study of metal-organic supramolecule has gained great recognition as an important interface between synthetic chemistry and materials science and provides asolid foundation for understanding how molecules can be organized and how functions can be achieved [1][2][3]. The current attention is focus on the construction of metal-organic frameworks (MOFs) with novel topology, and on the crystal engineering of molecular architectures organized by coordination bonds and supramolecular contacts (such as hydrogen bonding, p-p stacking interactions, etc.) [4,5]. In this work, H 2 CAM was employed as the major ligand because the unit has unique acoordination geometry, which can potentially provide more coordination motifs [6]. The title crystal structure is composited of one neodymium(III) ion, two CAM 2-ligands, three coordinated water molecules, and two lattice water molecules as well as af ree 4-hydroxypyridinium cation. Nd(III) is nine-coordinated with at ricapped trigonal prism configuration. The Nd atom is coordinated by two CAM molecules using four oxygen atoms of chaleated deprotonated carboxylate group and two nitrogen atoms of the pyridine ring, and three oxygen atoms from the water molucules, with d(Nd-O) rang from 2.480(2) to 2.560(2) Å,and d(Nd-N) rang from 2.567(2) to 2.581(2) Å,which are within normal ranges [6,7]. The angles of the CAM to the central ion range from 61.72(7)°to 123.62(7)°.T he dihedral angle between the two pyridyl rings attached to the central ion is 60.21°,and the dihedral angle between pyridyl rings attached to the central ion and the pyridyl ring of free 4-Hpy ligand vary from 63.59°to 68.18°.In both CAM ligands the dicarboxylate groups are almost coplanar, and the atoms in the pyridine deviate from the mean plane defined by the pyridine ring by less than 0.100 Å.D eviation from the mean plane defined by the pyridine ring are observed for both of carboxylate groups with values ranging from O4 -0.0641 to O2 +0.0893 Å.This implies that the CAM is afairly rigid ligand and retains its integrity on metal che...
Study Design Retrospective cohort study. Objective This study aimed to investigate the characteristics of microflora in patients with deep spinal surgical site infection (SSI) after prophylactic use of vancomycin powder (VP). Methods A retrospective analysis was performed on patients after spinal surgery. Patients were grouped according to whether VP use and only patients with deep SSI were included in this study. General information of the patients, the dose of vancomycin, bacterial culture results, drug sensitivity test results, and SSI treatment methods were recorded. The differences of microflora between the two groups were analyzed, and the sensitivity of bacteria in the +VP group to antibiotics was analyzed. Results The infection rate in the +VP group was 4.9% (56/1124) vs 6.3% (93/1476) in the No-VP group (P < 0.05). The proportion of Gram-positive bacteria (GPB) in the +VP SSIs was 55.4% vs.74.1% in the No-VP group (P < 0.05). The percentage of Gram-negative bacteria (GNB) in the +VP SSIs was 46.4% vs.30.1% in the No-VP group (P < 0.05). More dose of VP cannot decrease the SSI, but the proportion of GNB in VP >1g SSIs was higher (59.0% vs 32.4%, P < 0.05). In the +VP SSIs, all of the GNB cultured were sensitive to meropenem, and linezolid covered most of the GPB cultured. Conclusion Local use of vancomycin powder can reduce the incidence of SSI, but this may lead to changes in the bacterial flora. Once the SSI occurs, the case of GNB infection may be increased. The more dose of VP cannot decrease SSI but may increase the rate of GNB in the +VP SSIs. Once infections still occur after VP use, antibiotics covering GNB may be added. These findings may help guide choice of empiric antibiotics while awaiting culture data.
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