The aim of this study is to evaluate anti-tumor activities and mechanism of a novel kinase inhibitor ZLJ213 which targeted Aurora A and vascular endothelial growth factor receptor (VEGFR) in vitro and in vivo against human colon cancer. Results showed that ZLJ213 inhibited cell proliferation and induced cell cycle arrest and apoptosis of HCT1 16 and SW48 cell lines. In HCT116-derived xenograft, ZLJ213 dosed at 100 mg · kg(-1) inhibited tumor growth by 73.24%. The IC50 of ZLJ213 on the expression of p-Aurora A was 0.258 µmol · L(-1) analyzed by ELISA. Under the concentration of 0.08 µmol · L(-1), ZLJ213 could inhibit the activities of Aurora A, Histone H3 and VEGFR of HCT116 and SW48 cell lines. Simultaneously, ZLJ213 induced activation of Caspase 3 and PARP cleavage. Above data suggested that ZLJ213 had the ability to inhibit cell proliferation and induce cell apoptosis both in vitro and in vivo in colon cancer, and down-regulate the expression of p-Aurora A and p-VEGFR. ZLJ213 might be a potential therapeutic agent against colon cancer.
Animals ; Apoptosis ; Aurora Kinase A ; antagonists & inhibitors ; Cell Cycle Checkpoints ; Cell Line, Tumor ; drug effects ; Cell Proliferation ; Colonic Neoplasms ; pathology ; Humans ; Protein Kinase Inhibitors ; pharmacology ; Receptors, Vascular Endothelial Growth Factor ; metabolism ; Xenograft Model Antitumor Assays

ObjectiveTo study the expression changes of peripheral blood monocyte human leukocyte antigen DR (HLA-DR) in patients with severe craniocerebral injury,and investigate the correlation between HLA-DR expression and infection and prognosis.MethodsNinety patients with craniocerebral injury were selected as experimental group and were divided according to the Glasgow coma scale (GCS) score after hospitalization into experimental group 1 (GCS score 13-15 scores ),experimental group 2 (GCS score 9-12 scores) and experimental group 3 (GCS score 3-8 scores) with 30 patients each,which were moderate,medium,severe craniocerebral injury,respectively.Thirty healthy people were chosen at the same period as control group.The HLA-DR expression of experimental group was detected after 1,3,7 and 14 d of admission by flow cytometry,and the HLA-DR expression of control group was detected on the day they got physical examination.The rates of infection,cure,disability,vegetative state and mortality were counted after 30 d of admission.ResultsThe HLA-DR expressions in experimental group 1 and experimental group 2 after 1,3,7,14 d of admission were (28.11 ± 2.37),(26.45 ± 1.63),(27.75 ± 1.83),(27.15 ± 2.17) MCF and (29.34 ±2.07),(27.55 ± 1.63),(28.42 ± 1.94),(29.46 ±2.12) MCF,which had no statistical difference compared with that in control group [(29.18 ± 1.91 ) MCF](P＞ 0.05).The HLA-DR expressions in experimental group 1 and experimental group 2 after 1,3,7 d of admission and control group had statistical differences compared with those in experimental group 3 after 1,3,7 d of admission [(18.02 ± 1.78),(16.05 ± 1.97 ),(20.76 ± 1.65) MCF ] (P ＜ 0.05).The HLA-DR expressions in experimental group 1 and experimental group 2 after 14 d of admission and control group had no statistical significance compared with that in experimental group 3 after 14 d of admission [ (26.13 ± 2.15) MCF](P＞ 0.05).The infection rates of experimental group 1,experimental group 2 and experimental group 3 were 0,3.6％(1/28),82.8％(24/29),respectively,while the cure rates were 100.0％ (30/30),100.0％ (28/28),10.3％ (3/29),the disability rates were 0,0,41.4％ (12/29),the vegetative state rates were 0,0,20.7％ (6/29),and the mortality were 0,0,27.6％ (8/29).There was no statistical significance in the rates of infection,cure,disability,vegetative state and mortality between experimental group 1 and experimental group 2 (P＞ 0.05 ).While there was statistical differences in the rates of infection,cure,disability,vegetative state and mortality among experimental group 1,experimental group 2 and experimental group 3 (P ＜ 0.05).ConclusionsThe HLA-DR expression changes of patients with moderate and medium craniocerebral injury after 1,3,7,14 d of admission are not significant.The HLA-DR expression of patients with severe craniocerebral injury begins to decline from 1 d after injury,declines obviously at 3 d,increases from 7 d,returns to normal level at 14 d.The decline of HLA-DR expression in patients with severe craniocerebral injury is correlated with the infection,and predicts poor prognosis.

ObjectiveTo investigate the effects of fluid percussion injury(FPI) on survival and differentiation of transplanted human embryonic neural stem cells (HNSCs) in rats. MethodsThe HNSCs were separated from the cerebral cortex of the 8-week-old fetal and were cultured in DMEM/F12 combinated with EGF, bFGF and LIF. The rat models of FPI were made with fluid percussion system. The HNSCs labeled with BrdU were transplanted into the injured zone 24 hours after brain injury, then the rats were killed at the 1st and 4th week post-transplanted stages, and the brain slices were stained with immunocytochemistry. The GFAP, MAP-2, and BrdU positive cells were investigated.ResultsThe transplanted HNSCs migrated to the whole brain, and differentiated into GFAP and MAP-2 positive cells. MAP-2 positive cells were observed at 1 week post-transplanted stage, on the contrary, more GFAP positive cells were discovered 4 weeks after transplantation. Part of the HNSCs migrated to the choroids plexus of the lateral ventricle and microvessels. ConclusionThe transplanted HNSCs survive in the injured zone, and differentiate into astrocytes gradually during the recovery. The host devours part of the HNSCs.

Seizure-sensitive Fisher 344 rats were prepared 7 d after seizure episodes induced by a single subcutaneous administration of convulsive dose (7.5 mg/kg)of kainic acid. The activator protein-1 (AP-1) DNA binding activity and its components in the hippocampus of such rats were examined by Gel shift,Super-shift and Western blot assay. Gel shift assay showed that the basal level of AP-1 DNA binding activity was significantly higher than that of control rat hippocampus. Super-shift showed that only Fra and Jun D antibodies could super-shift AP-1 complex to a higher position. It suggested that the AP-1 complex was composed of Fra and Jun D in hippocampus of the seizure-sensitive rats. Western blot analysis further confirmed that Jun D proteins contained components of 43,39 and 28 kDa. When secondary seizure stimulations were given to seizure-sensitive rats, the AP-1 DNA binding activity was attenuated and the components of AP-1proteins changed transiently. In light of our results and those of literature, it appears that all the mentioned changes may play an important role in induction of long-lasting enhancement in seizure susceptibility.

Objective To observe the clinical efficacy and safety of tinidazole tablets combined with minocycline hydrochloride ointment in the treatment of chronic periodontitis.Methods Ninety-four patients with chronic periodontitis were randomly divided into control and treatment groups with 47 cases per group.Control group was filled with minocycline hydrochloride ointment in the periodontal pocket,once a week.Treatment group was treated with tnidazole 250 mg per time,qd,orally,on the basis of control group.Two groups were treated for 4 weeks.The clinical efficacy,levels of soluble intercellular adhesion molecule 1 (slCAM-1),interleukin-1 β (IL-11) in gingivil,monocyte chemoattractant protein -1 (MCP-1) and adverse drug reactions were compared between two groups.Results After treatment,total effective rates of treatment and control groups were 95.74％ (45 cases / 47 cases) and 80.85％ (38 cases / 47 cases) with significant difference (P ＜ 0.05).After treatment,the main indexes in treatment and control groups were compared:sICAM-1 were (87.64 ± 11.20) and (99.87 ± 14.52) μg · L-1,IL-1β were (25.66 ±4.21) and (34.81 ±4.16) μg · L-1,MCP-1 were (28.11 ±4.65) and (39.36 ±3.66) ng · L-1,the differences were statistically significant(all P ＜0.05).The adverse drug reactions of two groups were low blood pressure and headache.The total incidences of adverse drug reactions in treatment and control groups were 12.77％ and 14.89％ without significant difference (P ＞ 0.05).Conclusion Tinidazole tablets combined with minocycline hydrochloride ointment have a definitive clinical efficacy in the treatment of chronic periodontitis,which can significantly reduce the levels sICAM-1,IL-1β and MCP-1,without increasing the incidence of adverse drug reactions.

Objective To investigate the impact of age on patients with metabolic syndrome (MS) and normal persons. Methods Data was gathered from 8280 persons including 4873 males and 3407 females who were randomly selected. All subjects were devided into normal group and MS group. According to the interval of ten years, the subjects were devided into seven age groups, to calculate the difference of impaired fasting glycaemia (IFG) between patients with diabetes mellitus (DM) and normal people, as well as the related portions. Results (1) The risk of IFG and DM appeared to be different among age groups among the target subjects as well as in the normal and the MS groups (P<0.05). (2) Among the whole subjects, the overall prevalence of IFG was increasing with age. The prevalence of DM had an increasing trend with age augment in 20-79 years group, whereas a decreasing trend appeared in people over 80 years of age. (3) For normal persons, the prevalence of IFG and DM were all increasing with age augment in 20-79 years group, and then decreasing with age augment in the over-80-years group. (4)For MS patients, the prevalence of IFG had an increasing trend with age augment in 20-69 years group, whereas a decreasing trend appeared in people over 70 years of age. There was no tendency of variation with age augment in DM.Conclusions (1) For normal persons, high prevalence rates of IFG and DM were correlated to age augment, especially in senior persons. (2) For MS patients, high prevalence of IFG was also correlated to age augment, but no association between prevalence of DM and age augment was seen. (3)Age from 70 to 79 years appeared to be in high risk with MS.

OBJECTIVETo investigate the effect of rat Schwann cell secretion on the proliferation and differentiation of human embryonic neural stem cells (NSCs).

METHODSThe samples were divided into three groups. In Group One, NSCs were cultured in DMED/F12 in which Schwann cells had grown for one day. In Group Two, NSCs and Schwann cells were co-cultured. In Group Three, NSCs were cultured in DMEM/F12. The morphology of NSCs was checked and beta-tubulin, GalC, hoechst 33342 and GFAP labellings were detected.

RESULTSIn Group One, all neural spheres were attached to the bottom and differentiated. The majority of them were beta-tubulin positive while a few of cells were GFAP or GalC positive. In Group Two, neural spheres remained undifferentiated and their proliferation was inhibited in places where Schwann cells were robust. In places where there were few Schwann cells, NSCs performed in a similar manner as in Group One. In Group Three, the cell growth state deteriorated day after day. On the 7th day, most NSCs died.

CONCLUSIONThe secretion of rat Schwann cells has a growth supportive and differentiation-inducing effect on human NSCs.

Animals ; Brain ; cytology ; embryology ; Cell Differentiation ; drug effects ; Cell Division ; drug effects ; Coculture Techniques ; Humans ; Rats ; Rats, Sprague-Dawley ; Schwann Cells ; secretion ; Sciatic Nerve ; cytology ; Stem Cells ; cytology

OBJECTIVETo study the protective effect of Shenxiong injection on the cerebral ischemia-reperfusion injury of senile rats.

METHODTotally 108 Sprague-Dawley (SD) rats were randomly divided into the sham operation group, the model group, the Ni-modipine group and Shenxiong injection groups (low, middle, and high doses). The rat brain ischemia-reperfusion model was established by the middle cerebral artery occlusion (MCAO) method in rats, in order to observe the effect of Shenxiong injection on neurological score and brain infarct volume of rats with cerebral ischemia-reperfusion injury, and determine the contents of NOS, NO, SOD, MDA and LDH in brain tissues. The contents of TNF-alpha and IL-1beta levels in brain tissues were measured by enzyme-linked immunosorbent assay (ELISA) method.

RESULTShenxiong injection could significantly decrease neurological score, injury degree of brain tissues and brain infarct volume of rats with cerebral ischemia-reperfusion injury, increase the vigor of SOD, decrease the levels of MDA, NO, NOS and LDH, and inhibit IL-1beta and TNF-alpha expressions.

CONCLUSIONShenxiong injection has the obvious protective effect on the brain ischemia-reperfusion injury in rats. Its mechanism may be related to the improvement of neurological function, the reduction of free radical injury, and the inhibition of inflammation factor expression.

Animals ; Brain ; blood supply ; drug effects ; metabolism ; Brain Ischemia ; complications ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; therapeutic use ; Injections ; L-Lactate Dehydrogenase ; metabolism ; Male ; Malondialdehyde ; metabolism ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; complications ; drug therapy ; enzymology ; metabolism ; Superoxide Dismutase ; metabolism

Objective To explore the clinic application value of ultrasonography examination of optic nerve sheath diameter(ONSD) in brain injury.Methods From July 2008-June 2011,90 cases of brain injured patients were chosen as experimental group including light (A group),medium (B group),and heavy (C group) brain injured patients according to the admission GCS score ;50 cases of conventional physical examination and 90 cases of volunteers 50 in neurosurgical outpatient were chosen as control group.The ONSD of both groups were measured 3 mm behind the globe through orbital using color sonographic with different time after admission.3 times measurements were carried out for every optic nerve sheath.All client's ONSD mean and standard deviation were calculated.In 0.5 h after color dopplar ultrasound examination,lumbar vertebra puncturing measured intracranial pressure in different groups.Results After admission (1d,3 d,7 d,14 d),the ONSD of A group was (4.54 ±0.32)mm,(4.42 ±0.30)mm,(4.44 ±0.32) m,and (4.43 ± 0.25) mm,respectively; The ONSD of B groups was (4.48 ± 0.28) mm,(4.52 ± 0.24) mm,(4.46 ±0.28)mm,and (4.38 ±0.22)mm,respectively; The ONSD of C group was (5.67 ±0.35)mm,(6.36 ± 0.42) mm,(5.65 ± 0.23) mm,and (4.76 ± 0.35) mm,respectively.After admission (1 d,3 d,7 d,14 d),the intracranial pressure (IP) of A group was (82 ± 11) mmH2O,(79 ± 12) mmH2O,(90 ±15) mmH2O,and (86 ± 14) mmH2O,respectively; The IP of B group was (78 ± 15) mmH2O,(85 ± 10)mmH2O,(78 ± 16) mmH2O,(80 ± 11) mmH2O,The IP of C group was (225 ± 26) mmH2 O,(288 ± 23)mmH2O,(256 ± 23) mmH2O,(122 ± 18) mmH2O,respectively.Group D had the ONSD average of (4.58± 0.41)mm and IP of (88 ± 10)mmH2O after eyeball 3-mm place.No difference was found between A and B,A and D,or B and D (P＞0.05) ; A difference was found between A and C,B and C,or D and C (t =12.24～24.67,P＜0.01).Conclusions The ONSD and IP in light medium brain injured patients had no change.In patients with severe brain injury,IP changed with the time after injury,the ONSD increased with the IP,the ultrasonography examination of ONSD with the important value in the diagnosis and treatment can respond the IP increase,which is a non-invasion,convenient,fast,and feasible method for evaluation of cranial high pressure.

Objective To summarize the clinical experience in the replacement of the damaged sec- ond metacarpophalangeal joint with the second metatarsophalangeal joint with a pedicle of dorsal pedis artery and great saphcnous vein.Methods The damaged second metacarpophalangeal joint,distal part of the sec- ond metacarpal and proximal part of the proximal phalanx were dissected.The metatarsophalangeal joint was transferred to the region of metacarpophalangeal joint of hand.The dorsal pedis artery was anastomosed to the radial artery,and the great saphenous vein was anastomosed to the cephalic vein at anatomical snuff-box.The dissected bones of the hand removed of the cartilage of joint and soft tissue were grafted back to the donor site of the foot.Results A 5～30 month follow-up study in 8 out of 11 cases showed that satisfactory functional recovery was achieved in clinical practice.The movement of second metacarpophalangeal joint was excellent. Conclusion The function of the second metacarpophalangeal joint can be effectively recovered by the trans- fer of the vascularized second metatarsophalangeal joint.