Chemokines play pleiotropic roles in the pathology of Alzheimer′s disease(AD),a chronic inflammatory disease of central nervous system.The neuropathological features of AD include neurofibrillary tangles,amyloid plaques,neuroinflammation,and neuronal synaptic loss.Chemokines are involved in the pathogenesis of AD by activating or regulating inflammatory cells or glial cells,playing dual key roles of the pro-and anti-inflammatory properties in AD.The levels of chemokines in serum,cerebrospinal fluid and brain tissue of AD patients are changed accordingly.This review summarizes the role of chemokines and their receptors in AD in the biological activities and unveils the changing rules,aiming to provide new strategies for clinical treatment of AD.

Objective To investigate the relationship between cytochrome P 450 (CYP)2C19*2 / *3 gene polymorphism and antiplatelet effect of clopidogre in patients with ischemic stroke. Methods A total of 102 consecutive patients with acute ischemic stroke admitted to the Suzhou Integrated Traditional and Western Medicine Hospital from November 2012 to February 2014 were enrolled. The patients allergic to clopidogre,intolerant to clopidogrel,and recently using clopidogre were excluded. The patients were divided into a strong metabolic type group (n = 39),a moderate metabolic type group (n = 54),and a week metabolic type group (n = 9)according to the conditions of CYP2C19*2 and *3 locus mutation. The genotypes of the CYP2C19*2 and *3 were detected by the direct gene sequencing method in all patients. The maximum aggregation ratio (MAR)of platelet and platelet reactivity index (PRI)were detected beforeand 7 d after taking clopidogre 75 mg. Results (1)According to the CYP2C19*2 and CYP2C19*3, the genotyping was performed. The strong metabolic type group included *1 / *1 type 39 cases (38. 2%);the moderate metabolic type group included *l / *2 type 44 cases (43. 1%);*l / *3 54 cases, 10 (9. 8%);and the week metabolic type group included *2 / * type 27 cases (6. 9%);*2 / *3 type 2 cases (2. 0%). No *3 / *3 type was detected. (2)There were no significant differences in MAR before taking clopidogrel among the 3 groups (all P > 0. 05). After taking clopidogrel for 7 days,MAR and PRI were detected from strong to weak,followed by the week metabolic type group (49 ± 12% vs. 64 ± 15%), the moderate metabolic type group (42 ± 13% vs. 56 ± 14%),and the strong metabolic type group (33 ± 10% vs. 43 ± 12%);MAR was detected from high to low,followed by the strong metabolic type group (20 ± 12%),the moderate metabolic type group (10 ± 8%),and the week metabolic type group (7 ± 3%). Comparing the moderate metabolic type group and the week metabolic type group with the strong metabolic type group,there were significant differences between MAR,the decreased MAR and PRI (all P < 0. 01). Comparing the week metabolic type group with the moderate metabolic type group,there were no significant differences between MAR,the decreased MAR and PRI (all P > 0. 05). Conclusion The CYP2C19*2 and *3 gene polymorphisms may affect MAR and PRI after taking clopidogrel in patients with ischemic stroke.

Objective:To investigate the promotive effect of 4,5,6,7-tetrabromobenzotriazole (TBB) on the apoptosis of the human cervical cancer HeLa cells,and to clarify its effect mechanism in related signaling pathways.Methods:The human cervical cancer HeLa cells at logarithmic growth phase were divided into control group(without TBB) and experiment group(with TBB).MTT assay was used to detect the survival rate of the HeLa cells;the morphology of HeLa cells was observed under inverted microscope;Annexin Ⅴ-FITC/PI double staining and flow cytometry(FCM) were used to determine the apoptotic rates of the HeLa cells;the expression levels of apoptosis-related proteins p-Akt,Akt,Bcl-2,Bax,cleaved-caspase-3,and Pro-caspase-3 were detected by Western blotting method.Results:The MTT results showed that the survival rates of the HeLa cells in experiment group were significantly decreased(P<0.01) in a dose-dependent manner compared with control group.The apoptotic morphology of the HeLa cells in experiment group were found as cell shrinkage and karyopyknosis under inverted microscope.The Annexin Ⅴ-FITC/PI double staining and FCM results showed that the apoptotic rates of the HeLa cells in experiment group (3,6,12 and 24 h) were higher than that in control group (P<0.05 or P<0.01).The Western blotting results showed that compared with control group,the expression levels of the anti-apoptotic proteins p-Akt and Bcl-2 in HeLa cells in experiment group were decreased obviously,whereas the expression levels of the pro-apoptotic proteins Bax and cleaved-caspase-3 were increased and the expression levels of Pro-caspase-3 were decreased.Conclusion:TBB may promote the apoptosis of human cervical cancer HeLa cells by inhibiting the Akt signaling pathway.

Objective To study effects of the bacterial biofilm at different growth stages on dynamic behavior of the titanium partial ossicular replacement prosthesis (PORP), so as to provide theoretical references for clinical treatment of diseases such as secretory otitis media. Methods Based on the CT scan images of normal human right ear and combined with the self compiling program, a 3D finite element model of the ear was reconstructed for dynamic analysis on sound conduction, and compared with the experimental data. The model was computed by harmonic response analysis method, and the sound conduction effect of bacterial biofilm grown on PORP at different growth stages was analyzed. Results The simulated amplitude of umbo and stapes footplate was in accordance with experimental measurements, which confirmed the validity of this numerical model. The existence of biofilm would cause 0-1.6 dB hearing loss at low frequencies. The growth of biofilm in the radial direction of PORP would cause 0-12 dB hearing loss at intermediate and high frequencies, especially at 8 kHz, and the hearing loss could be as high as 11.2 dB. Conclusions The bacterial biofilm has an impact on hearing by reducing the hearing at low frequencies while raising a little at high frequencies. The biofilm grown in the radial direction of PORP will reduce hearing, and affect the working efficiency of PORP on hearing restoration.

BACKGROUND/AIMS: Evidence suggests that Shen-Kang (SK), a traditional Chinese herbal medicine, protects against various types of renal injury. In this study, we evaluated whether SK treatment confers renoprotection in a rat model of chronic tacrolimus (TAC) nephropathy. METHODS: Rats were treated daily with TAC (1.5mg/kg, subcutaneously) and SK (450 mg/kg, intravenously) for 4 weeks. The effects of SK on TAC-induced renal injury were assessed by measuring renal function, urine albumin excretion, histopathology, inflammatory cell infiltration, expression of profibrotic (transforming growth factor β1 [TGF-β1] and TGF-β inducible gene-h3 [βig-h3]) and proinflammatory cytokines, oxidative stress, and apoptotic cell death. RESULTS: Administration of SK preserved glomerular integrity (fractional mesangial area and Wilms tumor 1-positive glomeruli), attenuated tubulointerstitial fibrosis, and reduced the number of ectodermal dysplasia 1-positive cells, and this was paralleled by improved urine albumin excretion and renal dysfunction. At the molecular level, SK treatment suppressed expression of TGF-β1/Smad2/3, βig-h3, and proinflammatory cytokines. Oxidative stress and apoptotic cell death were significantly decreased with SK treatment, and apoptosis-related genes were regulated toward cell survival (active caspase-3 and the B-cell lymphoma-2/Bcl2-associated X [Bcl-2/Bax] ratio). CONCLUSIONS SK protects against TAC-induced renal injury.

Objectives: The purpose of this study was to compare differences in facial soft tissue thickness in three-dimensional (3D) images before and after orthognathic surgery in patients with skeletal Class III malocclusion and to obtain a better understanding of the relationship between hard and soft tissue changes after surgery.Materials and method: The present retrospective study included 31 patients with skeletal Class III malocclusion with mandibular chin deviation greater than 4 mm who had undergone cone-beam computed tomography before and 6 months after surgery. Seven bilateral points were established. Measurements were taken from software-generated multiplanar reconstructions. The predictor variables were timing (pre- and postoperatively) and side (deviated vs.nondedicated). A regression model and correlation analysis were conducted for statistical analysis. Results: The difference of bilateral facial soft tissue thickness was statistically significantly different between deviated and nondeviated sides (P < 0.05), with lower values observed on the deviated side. The soft tissue thickness has become nearly symmetric at local regions of the lower thirds of the face after orthognathic surgery. However, most measurements showed a negative correlation between changes in soft tissue thickness and changes in bone tissues. Conclusions Skeletal Class III malocclusion with facial asymmetry is accompanied by differences in soft tissue thickness when comparing Dev and N-Dev sides of the posterior region of the mandible, where soft tissues are thinner on the Dev side. Soft tissue thickness can compensate for or camouflage the underlying asymmetric mandible. In addition, the asymmetric soft tissue thickness on the lower third of the face can be partially improved by orthognathic surgery, but the amount of soft tissue thickness change is not consistent with that of hard tissue positional change.

The purpose of this study was to explore the clinical efficacy and safety of Gynostemma pentaphyllum (G. pentaphyllum) in the treatment of hyperlipidemia, and to provide systematic evaluation basis for clinical application. CNKI, Wanfang Data, VIP, Web of science, PubMed, Embase and Cochrane Library were searched for randomized controlled trials (RCTs) about G. pentaphyllum in the treatment of hyperlipidemia. Review Manager 5.4 were used for statistical analysis. Through reading topics, abstracts, and full texts, 27 papers with 2311 cases involved that met the inclusion and exclusion criteria were finally included for the analysis. In terms of curative effect, the effect of G. pentaphyllum alone in increasing high density lipoprotein (HDL) index was better than that of conventional treatment, and the effect of reducing total cholesterol (TC), triglyceride (TG) and low density lipoprotein (LDL) was similar to that of conventional treatment. There was a synergistic effect between G. pentaphyllum and conventional drugs, and the combination of G. pentaphyllum and conventional drugs was superior to conventional treatment in reducing TG and increasing HDL. G. pentaphyllum can also decrease the levels of serum glutamic pyruvic transaminase and glutamic oxaloacetic transaminase in the treatment of hyperlipidemia, indicating a certain protective function of the liver. In terms of safety, there were fewer cases of adverse reactions in the G. pentaphyllum treatment group, and the adverse reaction events reported in the literature was mild. According to the results of meta-analysis, G. pentaphyllum was effective in the treatment of hyperlipidemia, and it has the potential to be combined with traditional drugs, has a certain liver protection function, and was superior to traditional drugs in the treatment of hyperlipidemia.

Neural stem cells (NSCs) posse the specialty of tumor tropism and be able to migrate specifically to tumor cells. NSCs are also cross the blood brain barrier. NSCs keep in touch with tumor cells preferentially under the tumor microenvironment, and surround the target cells. Based on these characteristics, NSCs can be used as a carrier for therapeutic virus, enzymes/prodrugs, genes or suicide genes, etc. which are selectively delivered to the glioma cells. NSCs may be modified by a variety of different genes to establish a reliable, safe and effective therapy for glioma.

Objective:To investigate the promotion effect of 4,5,6,7-tetrabromobenzotriazole (TBB)on the apoptosis of human colon cancer SW480 cells,and to explore its possible mechanism.Methods:The human colon cancer SW480 cells at logarithmic growth phase were divided into control group (0 μmol·L-1 TBB)and experiment group (1,3,10,30,and 100 μmol·L-1 TBB).The viability of cells was measured by MTT assay;the apoptotic rate of the SW480 cells and the level of intracellular reactive oxygen species (ROS)were analyzed by Annexin Ⅴ-FITC/PI double staining and flow cytometry.The expression levels of anti-apoptotic proteins p-Akt and Bcl-2,and pro-apoptotic proteins Bad, pro-caspase-9 and cleaved-caspase-3 were detected by Western blotting method. Results:The MTT results showed that the viabilities of SW480 cells in experiment group were decreased in a dose-dependent manner,which were lower than that in control group (P < 0.05).The Annexin Ⅴ-FITC/PI double staining and flow cytometry results showed that the apoptotic rates of SW480 cells in experiment group (3,6,12, and 24 h)were significantly higher than that in control group (0 h)(P <0.05).The flow cytometry results showed the levels of ROS in SW480 cells after treated with TBB for 3,6,12 and 24 h were higher than that in 0 h group (P <0.05).The Western blotting results showed that the expression levels of anti-apoptotic proteins p-Akt and Bcl-2 in SW480 cells in experiment group (3,6,12,and 24 h)were decreased obviously,whereas the expression levels of the pro-apoptotic proteins Bad and cleaved-caspase-3 were increased and the expression level of pro-caspase-9 was decreased compared with those in control group (0 h) (P < 0.05 ).Conclusion: TBB could inhibit the cell proliferation and induce the apoptosis of human colon cancer SW480 cells,and its mechanism may be related to the inhibition of the activity of Akt and the promotion of the level of intracellular ROS.

OBJECTIVETo investigate quinalizarin-induced apoptosis in gastric cancer cells in vitro and explore the molecular mechanisms.

METHODSMTT assay was used to determine the cytotoxic effects of quinalizarin on human gastric cancer AGS, MKN-28 and MKN-45 cells. Annexin V-FITC/PI staining and flow cytometry were used to assess quinalizarin-induced apoptosis in AGS cells and its effect on intracellular ROS levels; the expression levels of apoptotic proteins in the cells were determined with Western blotting.

RESULTSQuinalizarin dose-dependently reduced the cell viabilities of the 3 gastric cancer cells (P<0.05). The ICvalues of quinalizarin in AGS, MKN-28 and MKN-45 cells were 7.07 µmol/L, 22.55 µmol/L and 14.18 µmol/L, respectively. Quinalizarin time-dependently induced apoptosis of AGS cells and potentiated the generation of intracellular reactive oxygen species (ROS) levels. Pretreatment with NAC, a scavenger of ROS, inhibited quinalizarin-induced apoptosis (P<0.001). Western blotting results showed that quinalizarin also up-regulated the expression levels of the apoptotic proteins including p-p38, p-JNK, Bad, cleaved caspase-3, and cleaved PARP-1 (P<0.05), and down-regulated the expression of the anti-apoptotic proteins p-Akt, p-ERK, and Bcl-2 (P<0.05).

CONCLUSIONQuinalizarin inhibits the proliferation and induces apoptosis in gastric cancer cells in vitro through regulating intracellular ROS levels via the MAPK and Akt signaling pathways.