Taking human umbilical vein endothelial cells (HUVEC)as experimental model which can simulate tumor-derived vascular endothelial cells;the effects of CPU-XT-008;an amino sugar derivative of combretastatin A-4 (CA-4);on HUVEC proliferation;cell cycle distribution;tubulin polymerization and the key regulatory pro-tein of cell cycle were studied.The effect of CPU-XT-008 on the proliferation of HUVEC was determined by MTT assay.The cell cycle distribution caused by CPU-XT-008 was detected by flow cytometry.Immunofluorescence was used to detect apoptosis and tubulin polymerization.The expressions of Cyclin B1;Cdc2 and β-tubulin were detected by Western blotting.Results demonstrated that CPU-XT-008 could target tubulin and inhibit the poly-merization ofβ-tubulin;and it could lead to G2/M cell cycle arrest in HUVEC by up-regulating Cyclin B1 expres-sion and down-regulating Cdc2 and p-Cdc2 expression;which resulted in inhibiting the proliferation of HUVEC and inducing its apoptosis.

Objective To compare clinical efficacy of inverse less invasive stabilization system (LISS) and Gamma nail in treating unstable femoral intertrochanteric fractures combined with lateral wall fractures.Methods Fifty-two patients with intertrochanteric fractures associated with lateral wall fractures followed up for at least 12 months after surgical treatment between June 2010 and June 2013 were included in this retrospective cohort study.According to the different internal fixation,the patients were assigned to inverse LISS group [16 males and 8 females;(62.5 ± 12.4)years] and Gamma nail group [17 males and 11 females;(60.4 ± 18.6)years].According to the AO classification,there were 6 patients with A2.2 type,5 A2.3 type,5 A3.1 type,6 A3.2 type and 2 A3.3 type in inverse LISS group,and there were 4 patients with A2.2 type,7 A2.3 type,9 A3.1 type,5 A3.2 type and 3 A3.3 type in Gamma nail group.Opcration time,total blood loss (intraoperaive plus occult blood loss),hospital length of stay,bone healing,time of commencing full weight-beating and complication incidence were compared between the two groups.Harris hip score was recorded postoperatively.Results All patients were followed up for 24-36 months (mean,30.2 months).Operation time in Gamma nail group was shorter than that in inverse LISS group (P ＜ 0.05),while relatively more blood loss was found in Gamma nail group(P ＜0.05).There were no significant differences in hospital length of stay and bone healing timebetween the two groups (P ＞ 0.05).Patients in Gamma nail groups started earlier full weight-bearing than inverse LISS group (P ＜0.05).Harris score was (86.1-± 12.4)points in inverse LISS group one year after operation,not significantly different from (83.3 ± 11.2) points in Gamma nail group (P ＞ 0.05).Complication of one patient with coxa vara and one bone nonunion in inverse LISS,showing no significant from one patient with screw breakage and one femoral head osteonecrosis in Gamma nail group (P ＞ 0.05).Conclusions Both techniques are effective in treatment of intertrochanteric fractures combined with lateral wall fractures and achieve similar results in function recovery.But inverse LISS is eccentric fixation,so too early weight-bearing should not be over-emphasized.

10.3969/j.issn.2095-4344.2013.26.007

In order to search for novel inhibitors of Na+/H+ exchanger isoform-1 (NHE-1), nine feruloylagmatine analogues were designed and synthesized from ferulic acid and agmatine. The structures of the synthesized compounds were confirmed by 1H NMR, 13C NMR and mass spectra, among which compounds 5f-5i were novel compounds. The results of preliminary pharmacological test showed that some of the compounds possessed strong NHE-1 inhibitory activity, among which compounds 5a, 5b and 6c were more potent than cariporide in NHE-1 inhibition.

Abstract: In the present study, the compound XL-12 from our previous work was utilized as a lead compound. Through the optimization of the terminal phenyl ring, 12 target compounds were designed and synthesized. The structures of all target compounds were confirmed by 1H NMR, 13C NMR, and H RMS. In vitro enzyme activity assay showed that most compounds demonstrated significant inhibitory activity toward Bruton’s tyrosine kinase (BTK) and Janus kinase 3 (JAK3). Among them, compound I-3 exhibited moderate cell proliferation inhibitory activity toward Daudi cells and BaF3-JAK3 cells. In the evaluation of anti-inflammatory activity in vitro, compound I-3 could effectively inhibit the production of inflammatory factors IL-6; besides, it exhibited superior anti-inflammatory activity compared to ibrutinib in xylene-induced ear swelling model in mice.

Alzheimer′s disease(AD)is a chronic neurodegenerative diseasecommonly seen in the elderlys. Several therapeutic drugs have failed in phase III clinical trials in recent years and there have been no efficient treatment for AD currently. Thus, there has been an urgent need for the effective methods of AD diagnosis at early stage. Developingnear-infrared fluorescentprobes for AD hallmarks detection has been a promising research field. In this review, we summarized a variety of near-infrared fluorescence(NIRF)probes reported in the past decade, which capable of detecting β-amyloid, Tau protein and reactive oxygen species, including their chemical strucutres、optical properties, in vitro and in vivo studies. Furthermore, we alsoraised some new directions for AD diagnosing. We believe that these new directions raised herein will benefit the future development of NIRF probes in the field of AD research.

Phosphoinositide 3-kindase,an important signal transduction molecule in cells,plays a key role in the process of cell survival,proliferation and differentiation.Significant progress has been made in the treatment of cancer with PI3K inhibitors,yet the drug resistance of PI3K inhibitors affects their long-term efficacy in clinical treatment.In order to overcome the drug resistance,a variety of rational combined therapies have been developed.In this paper,the research progress of phosphoinositide-3 kinase inhibitors in combination with other drugs to overcome the drug resistance were reviewed.

From January 2012 to January 2017,98 patients with clavicular fractures were treated with titanium elastic intramedullary nail(TEN),including 58 males and 40 females with an average age of 14.5 years (11-18 years).The mean time from injury to surgery was 4.2 d (2-7 d).Sixty nine cases were treated by closed reduction and 29 cases by 2-3 cm incision.Constant function scores and disability of the arm shoulder and hand (DASH) scores were compared before surgery and 4 wks after surgery;Neer function scores at 3 months after surgery were compared between the injured side and unaffected side.All patients were reexamined at a mean follow-up of 6.5 months (3-8 months),and fracture union was determined by X-ray.The results showed that the bony union was ranged from 8-16 weeks with an average of 12.4 weeks.There were 4 cases with soft tissue irritation;no cases of infection,TEN broken,delayed healing were observed.The Constant score rose from 41.7±4.8 before operation to 92.6±3.2 at 4 weeks after operation (t=16.67,P＜0.01);the DASH score rose from 3.8±2.1 before operation to 15.8±1.8 at 4 weeks after operation (t=8.59,P＜0.01).There was no significant difference in Neer score at 3 months after treatment between unaffected side and injured side (98.56±2.41 vs.97.45±3.32,t=1.64,P＞0.05).The TEN was removed after showing bone healing on X-ray film.The study indicates that using TEN has advantages of less invasiveness,reliable fixation and rapid functional improvement of shoulder for treatment of clavicular fracture in young and adolescent patients.

Extracellular signal-regulated kinase (ERK) is a kind of serine/threonine protein kinase. As a key downstream protein in RAS-RAF-MEK-ERK signaling pathway, its abnormal activation plays an important role in the development of tumors. Selective ERK1/2 inhibitors can block ERK signaling pathway while overcoming drug resistance caused by upstream target mutation. In this paper, the components of MAPK signaling pathway, the structure and functions of ERK and the role of ERK signaling pathway in tumor development are summarized, and some representative ERK inhibitors in clinical or preclinical studies are emphasized.