OBJECTIVE: To investigate the cytotoxic effect and its mechanism of the micromolecule compound on the leukemia cells. METHODS: The cytotoxic effects of 28 Nilotinib derivatives on K562, KA, KG, HA and 32D cell lines were detected by MTT assays, and the compound Nilo 22 was screen out. Cell apoptosis and cell cycle on leukemia cells were detected by flow cytometry. The effect of compound screened out on leukemogenesis potential of MLL-AF9 leukemia mice GFP RESULTS: Nilo 22 serves as the most outstanding candidate out of 28 Nilotinib derivatives, which impairs leukemia cell lines, but spares normal hematopoietic cell line. Comparing with Nilotinib, Nilo 22 could induce the apoptosis of GFP CONCLUSION Nilo 22 shows a significant cytotoxic effect on mice and human leukemia cells, especially for drug resistance cells. Nilo 22 is a promising anti-leukemia agent to solve the common clinical problems of drug resistance and relapse of leukemia.
Animals ; Apoptosis/drug effects* ; Cell Cycle/drug effects* ; Cell Line, Tumor ; Humans ; Leukemia ; Mice ; Myeloid-Lymphoid Leukemia Protein/genetics* ; Telomerase/metabolism* ; Telomere/metabolism*

Objective: To explore the diagnosis and clinical features of internal carotid artery aneurysm in the skull base. Methods: The data of 15 patients with internal carotid aneurysms in the skull base diagnosed and treated by digital subtraction angiography (DSA) or CT angiography (CTA) in the Provincial Hospital Affiliated to Shandong First Medical University from 1995 to 2017 were collected and analyzed. Among the 15 patients, 12 were males, and 3 were females, aging from 17 to 67 years old, with a median age of 44 years. Thirteen patients were diagnosed by DSA; the other two patients were diagnosed by CTA. Thirteen patients were diagnosed with pseudoaneurysm with the first symptom of epistaxis, in which eight patients underwent head trauma and 5 underwent radiotherapy of skull base tumor. The other two patients were diagnosed with true aneurysm presented headache and cranial nerve disorder. All patients were followed up for 2 to 12 years after treatment to see whether they were cured and survived. Results: Among the eight patients with a history of trauma, five patients were cured by embolization, two patients without embolization died of massive epistaxis, one patient died of progressive cerebral infarction after embolization. Among the five patients with radiotherapy of skull base tumor, one patient died of cerebral infarction after embolization, two patients died out of the hospital due to the recurrence of the primary tumor and intracranial invasion, one patient recovered well after embolization and surgical operation, one patient gave up treatment and died of massive hemorrhage out of hospital. In the other two patients with symptom of headache, one received embolization treatment outside the hospital after receiving mistake operation, and another one gave up treatment and died due to personal reasons. In total, four patients died in hospital, four died out of the hospital, and seven patients survived. Conclusions: Internal carotid artery aneurysm is a high-risk disease of anterior and middle skull base. For patients with epistaxis with a history of trauma and radiotherapy or patients with headaches and cranial nerve disorders, the possibility of the internal carotid artery aneurysm should be considered, in which DSA or CTA examination is essentially required for ensured diagnosis and disease evaluation.. The correct diagnosis and treatment by the otolaryngologist are crucial to the prognosis of the patient.
Adolescent ; Adult ; Aged ; Carotid Artery, Internal/diagnostic imaging* ; Female ; Humans ; Intracranial Aneurysm/therapy* ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Retrospective Studies ; Skull Base/diagnostic imaging* ; Young Adult

OBJECTIVE: To investigate the expression level of miR-181b in CD19+ B lymphocytes of patients with chronic lymphocytic leukemia (CLL), to analyze the relationship between its expression and the prognosis of CLL patients, and to predict the potential target gene of miR-181b in CLL by using bioinformatics. METHODS: Eight-four patients with CLL treated in People's Hospital of Xinjiang Uygur Autonomous Region from June 2013 to June 2018 were selected. and 20 healthy people were selected as control group. RNA was extracted from CD19+B lymphocytes of peripheral blood by magnetic bead sorting, the expression level of miR-181b was detected, and it's expression differences in different IPI groups were analyzed. The correlation between the expression level of miR-181b and PFS of CLL patients also was analyzed. miR-181b target genes were predicted by online database and literatures, and gene annotation analysis and relevant signal pathway analysis were performed for candidate target genes. RESULTS: The expression level of miR-181b in CLL patients was significantly lower than that in control group (P＜0.01); The expression level of miR-181b in the low-risk group was higher than that in high-risk group and extremely high-risk group (P＜0.05), but there was no statistical difference between low-risk group and medium-risk group (P=1.00). The expression level of miR-181b in medium-risk group was higher than that in high-risk group and extremely high-risk group (P＜0.05), but there was no difference between high-risk group and extremely high-risk group (P=1.00). ROC curve results showed that the area under the curve (AUC) was 0.792 (P＜0.01).When the expression level of miR-181b was at the threshold value of 0.279, it showed a better sensitivity (62.9%) and specificity (91.8%). Survival analysis results suggested that compared with the high expression group, the miR-181b low expression group had poor PFS (log rank: P=0.047). Prediction of miR-181b by using the starBase, targetscan and picTar database and its combination with literature reports indicated that CARD11, ZFP36L1, RUNX1, NR4A3, ATP1B1, PUM1 and PLAG1 related with blood diseases, and up-regulated CARD11 and ZFP36L1 participated in lymphoid tumor formation by promoting cell proliferation and inhibiting cell aging. CONCLUSION The expression level of miR-181b in CLL group are significantly lower than that in the controls group, and the low expression of miR-181b relates with poor prognosis of CLL patients. Through bioinformatics prediction and combined with literature reports, it is speculated that CARD11 and ZFP36L1 as target genes of miR-181b may be participated in the occurrence and development of CLL. Further experiments are needed to verify this result.
Apoptosis Regulatory Proteins ; Cell Proliferation ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; genetics ; MicroRNAs ; Prognosis

Objective:To construct the recombinant DNA E.coli ghosts (EBGs) expressing Treponema pallidum adhesin Tp0751 (pcD/Tp0751-BG) and determine its immunocompetence in immunized mice,and provide a potential novel method for syphilis vaccine developing.Methods:The recombinant eukaryotic expression plasmid pcDNA3.1(+)/Tp0751 was constructed and loaded into empty EBGs to create pcD/Tp0751-BG.The loading rate was determined accordingly.Macrophages cell line RAW264.7 was transfected with pcD/Tp0751-BG,and the expression of recombinant Tp0751(rTp0751) protein was detected by Western blot(WB).For immuno-competence in mice,the female BALB/c mice were randomly divided into 6 groups,including three control groups,A (PBS),B (EBG),C (empty pcDNA),and experimental group D(naked pcD/Tp0751),E (pcD/Tp0751-BG) and F (pcD/Tp0751-BG+rTp0751).All the mice were immunized as indicated for three times by intramuscular injection at two weeks intervals.The levels of specific IgG in sera and SIgA in genital tract lavage fluid were measured by ELISA.Levels of lymphocyte proliferation and IFN-γ secretion in spleen cells were measured by CCK-8 Cell Counting Kit and ELISA as well,respectively.Results:The loading rate of pcD/Tp0751 to EBGs was 76.1%.WB showed that the target recombinant protein pcD/Tp0751 expressed in RAW264.7 cells was active with Tp-infected rabbit sera.The titers of specific IgG and SIgA in group D,E,F gradually increased to significantly higher level as compared to the control groups (P<0. 01),which reached its peak at wk 8 after last immunization(the titers of IgG and SIgA were 1 :102 400 and 1 :12 800 in group F,respectively). Higher levels of specific IgG and SIgA were observed in groups E and F as compared to group D after first boost (P<0. 01),with groups F higher than group E after last boost(P<0. 01). At wk 8 after the last boost,the stimulation index (SI) and levels of IFN-γ in group D,E,F were all significant higher than the control groups (P<0. 01), with group E and F higher than group D (P<0. 01),and group E higher than group F (P<0. 05). Conclusion: The recombinant DNA EBGs of T. pallidum adhesin Tp0751 (pcD/ Tp0751-BG) possesses the immunocompetence to induce not only strong mucosal and systemic humoral immune response but also systemic cellular immune response in BALB/ c mice. The heterologous boost can be more efficient than homologous boost during immunization process.

Due to ineffectiveness and side effects of existing analgesics, chronic pain has become one of the most complex and difficult problems in the clinic. Monoacylglycerol lipase (MAGL) is an essential hydrolase in the endocannabinoid system and has been identified as a potential target for the treatment of pain. In the present study, we designed and synthesized twelve tanshinone IIA analogs and screened their activity against MAGL. Selected compounds were tested for analgesic activity in vivo, with the acetic acid writhing test model. Among the test compounds, compound III-3 (IC 120 nmol·L) showed significant activity against MAGL and ameliorated the clinical progression in the mouse pain model. Additionally, compound III-3, substitution with N-methyl-2-morpholinoacetamide, demonstrated improved solubility relative to tanshinone IIA.
Abietanes ; administration & dosage ; chemical synthesis ; chemistry ; Analgesics ; administration & dosage ; chemical synthesis ; chemistry ; Animals ; Chronic Pain ; drug therapy ; enzymology ; Drug Evaluation, Preclinical ; Enzyme Inhibitors ; administration & dosage ; chemical synthesis ; chemistry ; Female ; Humans ; Male ; Mice ; Mice, Inbred ICR ; Monoacylglycerol Lipases ; antagonists & inhibitors ; metabolism ; Structure-Activity Relationship

Insulin resistance is the pathophysiological basis of many diseases. Overcoming early insulin resistance highly significant in prevention diabetes, non-alcoholic fatty liver, and atherosclerosis. The present study aimed at evaluating the therapeutic effects of baicalin on insulin resistance and skeletal muscle ectopic fat storage in high fat diet-induced mice, and exploring the potential molecular mechanisms. Insulin resistance in mice was induced with a high fat diet for 16 weeks. Animals were then treated with three different doses of baicalin (100, 200, and 400 mg·kg(-1)·d(-1)) for 14 weeks. Fasting blood glucose, fasting serum insulin, glucose tolerance test (GTT), insulin tolerance test (ITT), and skeletal muscle lipid deposition were measured. Additionally, the AMP-activated protein kinase/acetyl-CoA carboxylase and protein kinase B/Glycogen synthase kinase 3 beta pathways in skeletal muscle were further evaluated. Baicalin significantly reduced the levels of fasting blood glucose and fasting serum insulin and attenuated high fat diet induced glucose tolerance and insulin tolerance. Moreover, insulin resistance was significantly reversed. Pathological analysis revealed baicalin dose-dependently decreased the degree of the ectopic fat storage in skeletal muscle. The properties of baicalin were mediated, at least in part, by inhibition of the AMPK/ACC pathway, a key regulator of de novo lipogenesis and activation of the Akt/GSK-3β pathway, a key regulator of Glycogen synthesis. These data suggest that baicalin, at dose up to 400 mg·kg(-1)·d(-1), is safe and able to attenuate insulin resistance and skeletal muscle ectopic fat storage, through modulating the skeletal muscle AMPK/ACC pathway and Akt/GSK-3β pathway.
AMP-Activated Protein Kinases ; metabolism ; Acetyl-CoA Carboxylase ; metabolism ; Adipose Tissue ; metabolism ; Animals ; Diet, High-Fat ; Flavonoids ; pharmacology ; Glycogen Synthase Kinase 3 beta ; physiology ; Insulin Resistance ; Male ; Mice ; Mice, Inbred C57BL ; Muscle, Skeletal ; metabolism ; Proto-Oncogene Proteins c-akt ; physiology ; Signal Transduction ; physiology

Objective To investigate the awareness of influenza knowledge,personal protection consciousness and behavior among young nurses in respiratory related departments.Methods One hundred and eight young nurses in respiratory related departments were investigated and analyzed by using the self-designed“questionnaire of influenza related knowledge and protective behavior”.Results The score of influenza related knowledge and behavior of young nurses was relatively low.The compliance rate of wearing masks was 95.37%. The accuracy of wearing masks was 79.63%.The compliance rate of hand hygiene was 47.54%.The percentage of young nurses accepting influenza vaccine was 32.40%.Conclusions The awareness rate of influenza related knowledge and behavior of young nurses is relatively low.Personal prote ctive consciousness and behavior need to be further improved.Hospitals need to strengthen the training of influenza related knowledge for young nurses and provide timely and effective protection.

OBJECTIVETo discuss the application and clinical effect of damage control concept in the treatment of severe limbs fractures combining with multiple trauma.

METHODSFrom July 2009 to July 2012, 30 patients with severe limbs fractures combining with multiple trauma were treated with the damage control concept, included 20 males and 10 females with an average age of (34.03 ± 12.81) years old ranging from 20 to 60 years old; the ISS averaged (35.00 ± 12.81) points (ranged from 26 to 54 points). And the control group also contained 30 patients with severe limbs fractures combining with multiple trauma treated by the traditional operation from June 2006 to June 2009, there were 23 males and 7 females with an average age of (34.23 ± 11.04) years old ranging from 18 to 65 years old. The ISS averaged (35.56 ± 11.04) points (ranged from 26 to 51 points). The age, gender, ISS, Gustilo classification, operation time, intraoperative blood loss, blood transfusion,postoperative complications and mortality rate were observed and compared.

RESULTSIn the damage control concept group,there were 28 cases surviving and 2 cases (6.7%) death; 6 cases of postoperative complication included 2 cases of adult respiratory distress syndrome, 1 case of multiple organ failure, 1 case of disseminated intravascular coagulation and 2 cases of wound infection. In the control group, there were 22 cases surviving and 8 cases death(26.7%); 13 cases of postoperative complication included 4 cases of adult respiratory distress syndrome,2 cases of multiple organ failure, 2 cases of disseminated intravascular coagulation and 3 cases of wound infection. There were no statistically significant differences between two groups in age, gender, ISS, Gustilo classfication and complication (P > 0.05), however there were statistically significant differences in mortality rate, operation time, blodd loss, blodd transfusion between two groups (P < 0.05).

CONCLUSIONDamage control concept is used to treat severe limbs fractures combining with multiple trauma which has the rapid and effective therapy, can improve survival rate and reduce complication.

Adolescent ; Adult ; Aged ; Embolism, Fat ; prevention & control ; Extremities ; injuries ; Female ; Humans ; Male ; Middle Aged ; Multiple Trauma ; surgery ; Postoperative Complications ; prevention & control

Objective To summarize the clinical features of non-classic infantile glycogen storage disease type Ⅱ for early diagnosis.Methods The clinical data including the clinical manifestations and investigation of the 3 nonclassic infantile glycogen storage disease type Ⅱ were retrospectively reviewed from Jun.to Jul.2011.All the 3 cases were diagnosed by measuring acid α-glucosidase (GAA) activity in blood sample.Results All the 3 patients presented development delay,limb muscle weakness without hepatomegaly.Two cases of them presented weakness of respiratory muscle.The serum creatine kinase,aspartate aminotransferase and alanine aminotransferase were high in all the 3 patients.Electromyography studies indicated that one of the patients with susceptible myopathy,one patient with neurogenic damage and one patient with mixed damage of the neuromascular.Echographic evidence of hypertrophic cardiomyopathy was detected in 2 patients.GAA activity of the 3 patients in blood sample had diagnostic value.Conclusions Nonclassic infantile glycogen storage disease type Ⅱ is easy to be missed due to its non-significant clinical manifestations.The results suggested that GAA activity in blood sample should be screened for the patients with motor development delay,decreased muscle weakness/exercise tolerance and increased of serum creatine kinase.

OBJECTIVETo study the effect of juglone on the ultrastructure of human liver cancer BEL-7402 cells.

METHODSBEL-7402 cells were incubated in the presence of 12.5 micromol/L juglone for 24 h, and fixed in 2.5% glutaraldehyde for HE staining and Coomassie brilliant blue staining and scanning electron microscopy.

RESULTSIncubation with juglone resulted in obvious changes in the cell morphology and cytoskeletal alterations of the cells. Scanning electron microscopy revealed reduced volume of the cell bodies, dissociation of the cells, curling and malformation of the microvilli on the cell surface with rupture of the intercellular junction and enlargement of the intercellular space. The formation of apoptotic bodies was observed. Transmission electron microscopy showed expansion of the endoplasmic reticula, mitochondrial cristea disintegration, nucleolar fragmentation and formation of the apoptotic bodies after the exposure to juglone for 24 h.

CONCLUSIONJuglone can cause ultrastructural changes of human liver cancer BEL-7402 cells and induce their apoptosis.

Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Humans ; Liver Neoplasms ; ultrastructure ; Naphthoquinones ; pharmacology