Acute Disease ; Anemia, Refractory ; etiology ; therapy ; Child ; Child, Preschool ; Cord Blood Stem Cell Transplantation ; methods ; Female ; Histocompatibility Testing ; Humans ; Leukemia ; complications ; pathology ; therapy ; Male ; Treatment Outcome

Blood Cell Count ; Bone Marrow Cells ; metabolism ; Child ; Cord Blood Stem Cell Transplantation ; Cytokines ; therapeutic use ; Histocompatibility Testing ; Humans ; Male ; Myelodysplastic Syndromes ; blood ; therapy ; Treatment Outcome

OBJECTIVETo discuss the present status and progress of clinical research on the cognitive effects caused by different types of brain tumors and common treatments.

DATA SOURCESThe data used in this review were mainly from PubMed articles published in English from 1990 to Febuary 2012. Research terms were "cognitive deficits" or "cognitive dysfunction".

STUDY SELECTIONArticals including any information about brain tumor related cognitive deficits were selected.

RESULTSIt is widely accepted that brain tumors and related treatments can impair cognitive function across many domains, and can impact on patients' quality of life. Tumor localization, lateralization, surgery, drugs, radiotherapy and chemotherapy are all thought to be important factors in this process. However, some conflicting findings regarding brain tumor-related cognitive deficits have been reported. It can be difficult to determine the mechanism of these treatments, such as chemotherapy, antibiotics, antiepileptics, and steroids. Future research is needed to clarify these potential treatment effects.

CONCLUSIONSCognitive function is important for patients with brain tumor. Much more focus has been paid on this field. It should be regarded as an important prognostic index for the patients with brain tumor, and neuropsychological tests should be used in regular examinations.

Brain Neoplasms ; physiopathology ; Cognition ; physiology ; Cognition Disorders ; physiopathology ; Glioma ; physiopathology ; Humans

BACKGROUND: The tooth ash can be used as a scaffold for bone tissue growth and provide calcium and phosphorus components during bone regeneration. Platelet-rich plasma can promote the soft and hard tissue regeneration. However, either of them has its shortcomings.OBJECTIVE: To investigate the effect of platelet-rich plasma combined with tooth ash in repairing skull bone defects. METHODS: Nine healthy rabbits were selected to make bone defects on both sides of the skull. Rabbit platelet-rich plasma combined with tooth ash was implanted into the skull defect on the left side as experimental group, while rabbit platelet-rich plasma was implanted into the skull defect on the right side as control group. Skull samples were taken out at 4, 6, 8 weeks after implantation for soft X-ray detection, hematoxylin-eosin staining and modified Gomori staining. RESULTS AND CONCLUSION: (1) Soft X-ray: The trabecular bone area of the experimental group was larger than that of the control group at 6 and 8 weeks after implantation (P < 0.05 or P < 0.01). (2) Hematoxylin-eosin staining: With the duration of implantation, newly formed fibers with bone structure gradually reduced at the defect sites in both groups, and there was a orderly layered arrangement in the bone structure and increased calcification. Compared with the control group, relatively higher new bone maturity, better bone trabecular arrangement and more osteoblasts were observed in the experimental group. (3) Modified Gomori staining: With the prolongation of implantation time, the new bone became mature gradually in the two groups, and the bone maturity in the experimental group was higher than that in the control group. To conclude, platelet-rich fibrin combined with tooth ash is better to promote bone defect repair.

OBJECTIVETo evaluate the clinical effect of umbilical cord blood transplantation (UCBT) in children with hematologic malignancies.

METHODSA retrospective analysis was performed on the clinical data of 37 pediatric patients with hematologic malignancies that consisted of 14 cases of acute lymphocyte leukemia, 9 cases of acute myeloid leukemia, 5 cases of juvenile myelomonocytic leukemia, 3 cases of chronic myeloid leukemia, 2 cases of acute mixed leukemia, 3 cases of myelodysplastic syndrome, and 1 case of lymphosarcomatous leukemia. Thirty-seven children with hematologic malignancies received UCBT from unrelated donors (34 cases) and related donors (3 cases). Grafts were 6/6 HLA-matched in 5 cases, 5/6 HLA-matched in 12 cases, 4/6 HLA-matched in 11 cases, and 3/6 HLA-matched in 9 cases. Before transplantation, these patients received rabbit antithymocyte globulin-containing conditioning regimen. The myeloablative conditioning regimen was given in 36 cases and the reduced-intensity conditioning regimen in one case. The median age of transplantation was 5.7 years, and the median weight was 20 kg. The grafts that contained a median of 6.2×10(7) total nucleated cells (TNC)/kg and 2.7×10(5) CD34(+) cells/kg were infused.

RESULTSThe median times to neutrophil engraftment and platelet engraftment were 12 days and 25 days, respectively, and the rates of neutrophil engraftment and platelet engraftment were 95% and 78%, respectively. The rate of neutrophil engraftment was positively correlated with the number of CD34(+) cells (P=0.011), while the rate of platelet engraftment was correlated with the numbers of CD34(+) cells and TNC (P=0.001; P=0.014). The incidence rates of acute and chronic graft-versus-host disease were 49% and 11%, respectively. The median follow-up was 54 months. The 5-year transplant-related mortality, overall survival, and disease-free survival were 27%, 57.4% and 41%, respectively.

CONCLUSIONSUCBT is an alternative source of hematopoietic stem cells for patients with hematologic malignancies.

Child ; Child, Preschool ; Cord Blood Stem Cell Transplantation ; adverse effects ; Female ; Follow-Up Studies ; Graft vs Host Disease ; epidemiology ; Hematologic Neoplasms ; mortality ; therapy ; Humans ; Infant ; Male ; Retrospective Studies

OBJECTIVEUnrelated umbilical cord blood has the clear benefits of rapid availability and a reduced stringency of requirement for HLA match. The aim of this study was to investigate the efficacy of unrelated umbilical cord blood transplantation (UCBT) in the treatment of malignant leukemia in children.

METHODSSix children with malignant leukemia, including three cases of acute lymphocyte leukemia [two high-risk patients and one standard-risk patient in complete remission (CR)], two juvenile myelomonocytic leukemia (one in CR and one in the accelerating stage), and one acute myeloblastic leukaemia (in CR), received a UCBT. The umbilical cord blood grafts were HLA-matched (n=1) or HLA-mismatched at 1 (n=1) or 2 (n=1) or 3 (n=3) loci. Busulfan/cyclophosphamide/antithymocyte globulin (ATG) or total body irradiation (TBI)/cyclophosphamide/ATG was involved in the myeloablative pretreatment regimen. The median infused donor nucleated cell was 8.51 x 10(7)/kg of recipient weight, and the CD34+ cell was 1.81 x 10(5)/kg of recipient weight. Cyclosporin, corticoid, mycophenolate mofetil and daclizumab were used for prophylaxis of acute graft versus host disease (GVHD).

RESULTSThe time to reach an absolute neutrophil count of 0.5 x 10(9)/L ranged from 11 to 35 days (median: 13 days) and the time to reach a platelet count of 20 x 10(9)/L ranged from 27 to 68 days (median: 30 days) after transplantation, and the donors' hematopoietic stem cells were shown in these patients. Four patients developed grade I to III acute GVHD but responded to steroids and daclizumab. Chronic GVHD was not found during a 3-16-month follow-up. Four patients survived and did not relapse during the follow-up.

CONCLUSIONSUnrelated umbilical cord blood is an alternative source of hematopoietic stem cells for patients with leukemia. UCBT can tolerate 1-2 HLA mismatches. The incidence of acute GVHD is high in UCBT recipients.

Child ; Child, Preschool ; Cord Blood Stem Cell Transplantation ; adverse effects ; Female ; Follow-Up Studies ; Graft vs Host Disease ; etiology ; Hematopoiesis ; Humans ; Infant ; Leukemia ; therapy ; Male

Cord Blood Stem Cell Transplantation ; adverse effects ; Graft vs Host Disease ; etiology ; Histocompatibility Testing ; Humans ; Infant ; Male ; Osteopetrosis ; etiology ; therapy ; Transplantation, Homologous

This study investigated the effect and mechanism of morin in inducing autophagy and apoptosis in hepatocellular carcinoma cells through the protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/signal transducer and activator of transcription protein 3(STAT3) pathway. Human hepatocellular carcinoma SK-HEP-1 cells were stimulated with different concentrations of morin(0, 50, 100, 125, 200, and 250 μmol·L~(-1)). The effect of morin on the viability of SK-HEP-1 cells was detected by Cell Counting Kit-8(CCK-8). The effect of morin on the proliferation and apoptosis of SK-HEP-1 cells was investigated using colony formation assay, flow cytometry, and BeyoClick~(TM) EdU-488 with different concentrations of morin(0, 125, and 250 μmol·L~(-1)). The changes in the autophagy level of cells treated with morin were examined by transmission electron microscopy and autophagy inhibitors. The impact of morin on the expression levels of proteins related to the Akt/mTOR/STAT3 pathway was verified by Western blot. Compared with the control group, the morin groups showed decreased viability of SK-HEP-1 cells in a time-and concentration-dependent manner, increased number of apoptotic cells, up-regulated expression level of apoptosis marker PARP, up-regulated phosphorylation level of apoptosis-regulating protein H2AX, decreased number of positive cells and the colony formation rate, an upward trend of expression levels of autophagy-related proteins LC3-Ⅱ, Atg5, and Atg7, and decreased phosphorylation levels of Akt, mTOR, and STAT3. These results suggest that morin can promote apoptosis, inhibit proliferation, and induce autophagy in hepatocellular carcinoma cells, and its mechanism of action may be related to the Akt/mTOR/STAT3 pathway.
Humans ; Proto-Oncogene Proteins c-akt/metabolism* ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; TOR Serine-Threonine Kinases/metabolism* ; Apoptosis ; Autophagy ; Cell Proliferation ; Cell Line, Tumor ; STAT3 Transcription Factor/metabolism*

This study aimed to investigate the effect and molecular mechanism of sinomenine on proliferation, apoptosis, metastasis, and combination with inhibitors in human hepatocellular carcinoma HepG2 cells and SK-HEP-1 cells. The effect of sinomenine on the growth ability of HepG2 and SK-HEP-1 cells were investigated by CCK-8 assay, colony formation assay, and BeyoClick~(TM) EdU-488 staining. The effect of sinomenine on DNA damage was detected by immunofluorescence assay, and the effect of sinomenine on apoptosis of human hepatocellular carcinoma cells was clarified by Hoechst 33258 staining and CellEvent~(TM) Cystein-3/7Green ReadyProbes~(TM) reagent assay. Cell invasion assay and 3D tumor cell spheroid invasion assay were performed to investigate the effect of sinomenine on the invasion ability of human hepatocellular carcinoma cells in vitro. The effect of sinomenine on the regulation of protein expression related to the protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/signal transducer and activator of transcription 3(STAT3) signaling pathway in HepG2 and SK-HEP-1 cells was examined by Western blot. Molecular docking was used to evaluate the strength of affinity of sinomenine to the target cysteinyl aspartate specific proteinase-3(caspase-3) and STAT3, and combined with CCK-8 assay to detect the changes in cell viability after combination with STAT3 inhibitor JSI-124 in combination with CCK-8 assay. The results showed that sinomenine could significantly reduce the cell viability of human hepatocellular carcinoma cells in a concentration-and time-dependent manner, significantly inhibit the clonogenic ability of human hepatocellular carcinoma cells, and weaken the invasive ability of human hepatocellular carcinoma cells in vitro. In addition, sinomenine could up-regulate the cleaved level of poly ADP-ribose polymerase(PARP), a marker of apoptosis, and down-regulate the protein levels of p-Akt, p-mTOR, and p-STAT3 in human hepatocellular carcinoma cells. Molecular docking results showed that sinomenine had good affinity with the targets caspase-3 and STAT3, and the sensitivity of sinomenine to hepatocellular carcinoma cells was diminished after STAT3 was inhibited. Therefore, sinomenine can inhibit the proliferation and invasion of human hepatocellular carcinoma cells and induce apoptosis, and the mechanism may be attributed to the activation of caspase-3 signaling and inhibition of the Akt/mTOR/STAT3 pathway. This study can provide a new reference for the in-depth research and clinical application of sinomenine and is of great significance to further promote the scientific development and utilization of sinomenine.
Humans ; Carcinoma, Hepatocellular/genetics* ; Proto-Oncogene Proteins c-akt/metabolism* ; Caspase 3/metabolism* ; Liver Neoplasms/genetics* ; Molecular Docking Simulation ; Sincalide/pharmacology* ; Cell Line, Tumor ; Cell Proliferation ; Hep G2 Cells ; TOR Serine-Threonine Kinases/metabolism* ; Apoptosis