Objective To investigate the effects of alantolactone on cell proliferation,cell-cycle and cell cycle-related proteins in human chronic myelogenous leukemia drug-resistant cell line K562/ADR.Methods K562/ADR cells were treated with 0,1.0,2.0,4.0,6.0,8.0,and 10.0 μmol/L of alantolactone for 12,24 and 48 h,with its cell viability analyzed by MTT assay.Flow cytometry was used to examine the effect of alantolactone on the cell-cycle of K562/ADR cells.The cell cycle-related proteins were analyzed by using Western blot after treatment with alantolactone.Results The results of MTT showed that alantolactone effectively inhibited the proliferation of K562/ADR cells in dose and time-dependent way,and the IC50 value of alantolactone in K562/ADR cells was about 5 μmol/L.Flow cytometric analysis displayed that alantolactone could arrest cell cycle at G2/M phase.The percentage of accumulated cells in the G2/M phase was increased from (15.8±1.7) ％ in the control group to (21.0±2.4) ％,(26.4±2.7) ％,and (30.1±3.9) ％ in cells treated with 2.5,5.0,and 7.5 μmol/L of alantolactone for 24 h,respectively (P ＜ 0.05).Alantolactone significantly decreased the expression of CDK1 and CyclinB1 and increased the expression of cyclin-dependent kinase inhibitor p21.Meanwhile,the treatment of K562/ADR with alantolactone led to a dose-dependent decrease in bcr-abl protein levels.Conclusion Alantolactone can significantly inhibit the proliferation and cell-cycle arrest in G2/M phase of K562/ADR cells,in which mechanism may be associated with the regulation of cell cycle-related proteins and downregulation of bcr-abl protein.

AIM　To study the structures of the epimerides of cycloclausenamide. METHODS　The structures of compound I, extracted from Clausena lansium (Lour.) Skeels, and synthesized compound III were determined by single crystal X-ray diffraction analysis. The stereo-structures of compound II and IV were also built up through Tripos force field based on crystal structures of compound I and III. RESULTS　The molecular formula and molecular weight were found to be C18H17O2N and 279.34 respectively. Compound I crystallized in monoclinic system, space group P21 with a=0.5928(1), b=1.5014(1), c=1.6190(1) nm, V=1.4410(3) nm3, Z=4, Dx=1.288 g*cm-3, Rf=0.075, Rw=0.073(w=1/σ2｜F｜), S=3.983; compound III crystallized in triclinic system, space group P1 with a=0.5667(1), b=1.2934(1), c=2.1119(1) nm, α=102.17(1), β=90.25(1), γ=102.65(2)°, V=1.4770(5) nm3, Z=4, Dx=1.224 g*cm-3, Rf=0.047, Rw=0.051(w=1/σ2｜F｜), S=0.467. CONCLUSION　These results showed that compound I and III both are cycloclausenamide except that the directions of the phenyl group on C6 are different. Cycloclausenamide can form 4 pairs of epimerides but the directions of the phenyl group does not affect their energy in free state.

Objective To investigate whether the presence of infection in a case series with coma would predict sepsis associated encephalopathy(SAE).Methods From Jan 2013 to Oct 2014,we used the criteria of systemic inflammatory response syndrome (SIRS)positive sepsis with encephalopathy and retrospective diagnosed a comatose case series with infection and from a tertiary teaching hospital intensive care unit (ICU).Results Among 6 comatose patients with evidence of infection,3 cases were secondary infection after hemorrhagic stroke,1 case was secondary infection after trauma,and the other 2 cases were primary infection.All patients met the diagnosis of SIRS -positive sepsis with encephalopathy.Among them,the presence of SIRS 3 criteria was in 2 cases,four criteria in 4 cases. All patients with severe brain failure (100%),in addition to 5 cases with acute respiratory failure caused by lung injury,one case with acute liver failure.Brain imaging confirmed that the delayed vasogenic edema was in two cases (33.3%),the cerebral ischemic lesions in four cases(66.7%).The ischemic lesion included 1 patient with minor infarcts and 1 case with mild white matter lesions,and with a good prognosis.The other two ischemic cases included multifocal leukoencephalopathy with central pontine myelinolysis in 1 case and extensive white matter lesions in 1 case,eventually with a poor prognosis.Conclusion SAE is a common critically illness,the use of the new classifi-cation criteria of sepsis is helpful in the diagnosis of sepsis associated encephalopathy.

Objective To explore the value of superb microvacular imaging ( SMI) technology in differentiating thyroid microcarcinomas from benign micronodules comparing with contrast‐enhanced ultrasound (CEUS) . Methods A total of 195 thyroid micronodules ( ≤1 .0 cm) from 172 patients were examined using CEUS and SMI ,and the findings were reviewed and evaluated in comparison to the pathological results . Results Of all the 195 thyroid nodules ,pathologic findings revealed that 140 (71 .8% ) were malignant and 55 (28 .2% ) were benign ,CEUS diagnosed that 127 (65 .1% ) were malignant and 68 (34 .9% ) were benign ,and SMI diagnosed that 129 (66 .2% ) were malignant and 66 (33 .8% ) were benign . There were no differences between the SMI and CEUS in terms of sensitivity ( 90 .0% vs 87 .9% ) , specificity ( 94 .5% vs 92 .7% ) ,accuracy ( 91 .3% vs 89 .2% ) ,positive predictive value ( 97 .7% vs 96 .9% ) and negative predictive value ( 92 .9% vs 87 .9% ) ( P > 0 .05 for all) . Conclusions SMI can effectively observe the perforating blood vessels of thyroid micronodules , which plays an important role in differentiating of benign and malignant thyroid micronodules .

Objective:To apply the best evidence of hypoglycemia management for neonates delivered by mothers with gestational diabetes mellitus (GDM) in clinical practice and evaluate its curative effects.Methods:This study was a historical controlled study. The newborns delivered by GDM mothers who were admitted to the neonatal intensive care unit of a Class A hospital in Hefei from February to December 2019 were selected as the research objects by convenient sampling. Newborns delivered by GDM mothers admitted to the hospital during the application of evidence-based practice were the subjects of the pre-evidence study ( n=53) , and newborns delivered by GDM mothers admitted to the hospital after applying the evidence-based practice from September to December 2019 were used as evidence Post-application research subjects ( n=59) . Evidence-based nursing was used to obtain best evidence. Based on the evidence-based continuous quality improvement model as the theoretical framework, the evidence-based practice plan for neonatal hypoglycemia management of gestational diabetes mothers during delivery was constructed and applied. Before and after the application of evidence-based practice, 63 neonatal nurses and parents of neonates were surveyed with the self-made GDM Mothers' Newborn Hypoglycemia Management Questionnaire and the Chinese version of the Uncertainty of the Disease Parents Scale, respectively. And the changes in the incidence of hypoglycemia within 2 hours after birth was compared before and after the application of evidence-based practice. Results:A total of 7 pieces of evidence were used in the evidence-based practice. After the application of the evidence-based practice, the incidence of hypoglycemia in neonates delivered by mothers with gestational diabetes within 2 hours after birth decreased from 20.8% (11/53) to 3.4% (2/59) , and the difference was statistically significant (χ 2=8.206, P<0.05) . The score of the questionnaire on knowledge of hypoglycemia management of neonates delivered by mothers with gestational diabetes mellitus in 63 department nurses was increased from (7.00±1.43) to (7.84±1.18) , and the difference was statistically significant ( t=-12.253, P<0.05) . Before and after the application of evidence-based practice, scores of Mishel Uncertainty in Illness Scale for newborn parents were respectively 87.00 (65.00, 99.50) and 59.00 (43.00, 74.00) , and the difference was statistically significant ( U=728.500, P<0.01) . Conclusions:Evidence-based practice for blood glucose management of newborns delivered by gestational diabetic mothers can reduce the incidence of neonatal hypoglycemia and the uncertainty of their parents' diseases, improve nurses' neonatal hypoglycemia management level, and promote continuous improvement of nursing quality.

OBJECTIVETo explore the inhibitory effect of alantolactone on the proliferation of adriamycin-resistant human chronic myelogenous leukemia cell line K562/ADR cells and its mechanism.

METHODSK562/ADR cells were treated with various concentrations of alantolactone (0, 1, 2, 4, 6, 8, and 10 μmol/L) for different time points. Cell viability was analyzed with MTT assay. The effect of alantolactone on the apoptosis of K562/ADR cells was measured by flow cytometry. The expression of apoptosis-related proteins after treatment with alantolactone was analyzed using Western blot.

RESULTSAlantolactone could effectively inhibit the proliferation of K562/ADR cells in dose- and time- dependent manner, the IC50 value of alantolactone treatment of K562/ADR cells for 24 h was 4.7 μmol/L (P<0.05). Flow cytometric analysis displayed that the apoptotic rates were 1.35%, 16.91%, 29.61% and 46.26%, respectively, after treatment with alantolactone at 0, 2.5, 5 and 7.5 μmol/L. Meanwhile, the expression of Bcl-2 and BCR-ABL proteins were significantly decreased and that of Bax, cytochrome C, cleaved-caspase-9, cleaved-caspase-3 and cleaved-PARP increased by alantolactone treatment.

CONCLUSIONAlantolactone had obvious inhibitory effect on the proliferation of K562/ADR cells through the caspase dependent mitochondrial(or intrinsic)apoptotic pathway.

Apoptosis ; Caspase 3 ; metabolism ; Caspase 9 ; metabolism ; Cell Proliferation ; drug effects ; Fusion Proteins, bcr-abl ; metabolism ; Humans ; K562 Cells ; Lactones ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Sesquiterpenes, Eudesmane ; pharmacology ; bcl-2-Associated X Protein ; metabolism