Aim To study the effect of novel AChE inhibitors, 2-phenoxy-indan-1-one derivatives (YKY-1~7), against glutamatic acid-induced neurotoxicity in PC12 cells and on learning & memory impairment in dementia model mice induced by A?25~35 icv Methods The PC12 cells were preincubated with different concentrations of YKY-1~7 for 24 h and subsequently treated by glutamatic acid, at the high concentration of 2 mmol?L-1 for 15 min to induce cytotoxicity. The cell viability was assessed with MTT method.. Dementia model mice were made by intracerebroventricular injection (icv) of aggregated A?25~35. From the next day, the model mice were administered YKY-7 (2.5, 5, 10 mg?kg-1, ig) for 10 consecutive days and sham control mice or A? model control mice received daily ig saline. After the final treatment, the passive avoidance learning was tested, regional cerebral blood flow at cerebral cortex was assessed, and the activity of AChE in the cerebral cortex, hippocampus and blood serum were determined. Results Six out of the seven YKY compounds appeared to be effective against glutamatic acid-induced neurotoxicity in PC12 cells, with YKY-7 demonstrating the most activity. YKY-7 significantly ameliorated the learning and memory ability in dementia model mice induced by A?25-35 icv, slightly and selectively inhibited the cortical and hippocampal AChE, and gently increased the blood flow at cerebral cortex. Conclusion Some of 2-phenoxy-indan-1-one derivatives reported here have protective effects against glutamatic acid induced neurotoxicity in PC12 cells, and improve the learning and memory impairment induced by A?25-35, which may be partly attributable to its selective inhibition of AChE activity in the cerebral cortex and hippocampus.

Objective To investigate the correlation between retraction phenomenon on the coronal planes obtained by an automated breast volume scanner ABVS and biological behaviors of breast cancer Methods Two hundred and eighty-eight female patients with 293 pathologically proven breast cancers were included in this study All of them underwent ABVS examinations before surgery Retraction phenomenon on the coronal planes was evaluated retrospectively Correlation between retraction phenomenon and hormone receptor HR human epidermal growth factor receptor 2 HER-2 Ki-67 molecular subtypes histologic type histologic grade lymph node status lesion size and patient age were evaluated by univariate logistic regression analysis Above significant variables were then enrolled in multivariate logistic regression analysis to select independent risk factors for retraction phenomenon Results By univariate logistic regression analysis Luminal A subtype odds radio OR =8 395 P <0 001 HR positive OR=4 876 P <0 001 HER-2 negative OR = 4 407 P < 0 001 lower expression of Ki-67 OR = 3 716 P <0 001 lower grade OR=3 574 P <0 001 lymph node invasion OR=2 053 P =0 004 and smaller lesion OR=1 762 P =0 033 were risk factors for retraction phenomenon while histologic type P =0 3 1 8 and patient age P = 0 612 were not By multivariate logistic regression analysis Luminal A subtype OR=9 877 P <0 001 lower grade OR=3 573 P <0 001 and lymph node invasion OR=2 730 P = 0 004 were independent risk factors for retraction phenomenon among which Luminal A subtype was the strongest one Conclusions Retraction phenomenon on the coronal planes obtained by ABVS is closely related with Luminal A subtype and may be an imaging feature of less aggressive behaviors of breast cancer.

Objective To compare the application value of three different planes obtained by automated breast volume scanner for the observation of margin characteristics of breast masses.Methods Two hundred and eight women patients with 237 masses (120 benign and 1 1 7 malignant,confirmed by pathology)were included in this study.The detection rates of mass margin characteristics in three different planes were compared.The diagnostic performance of mass margin characteristics in differentiating benign and malignant breast masses in three different planes was compared by area under the ROC curve (AUC). Results The detection rate of angular margins for malignant masses in sagittal planes(41 .9%)was higher than that in coronal planes(22.2%)and axial planes(26.5%)with statistical difference (P =0.001 ,0.013);the detection rate of spiculated margins for malignant masses in coronal planes(42.7%)was higher than that in sagittal planes (1 1 .1 %)and axial planes (1 7.1 %)with statistical difference (both P < 0.001 ).No significant difference was found between any two of the three planes in the detection rates of margin characteristics for benign masses.The AUC of angular margins in sagittal planes (0.693)was higher than that in coronal planes (0.607)and axial planes (0.624);the AUC of spiculated margins in coronal planes (0.697)was higher than that in sagittal planes (0.55 1 )and axial planes (0.573 );the AUC of indistinct margins in axial planes(0.606)was higher than that in coronal planes (0.552)and sagittal planes (0.552);the AUC of microlobulated margins in axial planes (0.825)was higher than that in coronal planes (0.778) and sagittal planes (0.81 7).Conclusions Three different planes of ABVS have their own advantages for the observation of margin characteristics of breast masses.

The present study was designed to target fish for potential bioactive components contained in a Huang Lian Jie Du decoction (HLJDD) and identify the underlying mechanisms of action for the treatment of sepsis at the molecular level. he bioactive components database of HLJDD was constructed and the sepsis-associated targets were comprehensively investigated. The 3D structures of the PAFR and TXA2R proteins were established using the homology modelling (HM) method, and the molecular effects for sepsis treatment were analysed by comparing the bioactive components database and the sepsis targets using computational biology methods. The results of the screening were validated with biological testing against the human oral epidermal carcinoma cell line KB in vitro. We found that multiple bioactive compounds contained in the HLJDD interacted with multiple targets. We also predicted the promising compound leads for sepsis treatment, and the first 28 compounds were characterized. Several compounds, such as berberine, berberrubine and epiberberine, dose-dependently inhibited PGE2 production in human KB cells, and the effects were similar in the presence or absence of TPA. This study demonstrates a novel approach to identifying natural chemical compounds as new leads for the treatment of sepsis.
Anti-Inflammatory Agents, Non-Steroidal ; pharmacokinetics ; Berberine ; analogs & derivatives ; pharmacokinetics ; Dinoprostone ; biosynthesis ; Drugs, Chinese Herbal ; chemistry ; pharmacokinetics ; Humans ; KB Cells ; Platelet Membrane Glycoproteins ; drug effects ; Protein Transport ; Receptors, G-Protein-Coupled ; drug effects ; Receptors, Thromboxane A2, Prostaglandin H2 ; drug effects ; Sepsis ; drug therapy ; metabolism ; Tetradecanoylphorbol Acetate ; pharmacokinetics

OBJECTIVETo investigate the effect of clopidogrel on the binding rate of ginsenosides with rat serum proteins (RSA).

METHODSEquilibrium dialysis and liquid chromatography-mass spectrometry were employed to quantify the concentration of ginsenoside Rg1 and Rb1. The protein-binding rates of Rg1 and Rb1 in the presence or absence of clopidogrel (1.0 mg/L) were determined. A molecular simulation model (consisting of homology modeling and molecular docking interaction) was used to reveal the target protein-compound interactions.

RESULTSThe binding rates of ginsenosides Rg1 (0.4, 1.0, and 2.0 mg/L) with RSA were (30.16∓2.82)%, (33.42∓4.21)%, and (34.61∓3.42)%, and those of and Rb1 were (50.13∓2.34)%, (51.23∓3.23)%, and (53.11∓3.26)%, respectively. In the presence of clopidogrel, the binding rates of Rg1 decreased to (22.13∓2.72)%, (21.42∓3.22)%, and (25.45∓3.52)%, and those of Rb1 to (40.13∓3.24)%, (41.25∓4.15)%, and (43.11∓3.31)%, receptively. The molecular docking suggested that these compounds competed to bind with RSA.

CONCLUSIONClopidogrel can competitively bind to RSA with ginsenosides to lower the plasma protein binding rates of ginsenosides.

Objective To evaluate the effectiveness of automated breast volume scanner(ABVS) and magnetic resonance imaging(MRI) in the detection and diagnosis of breast cancer and to assess the value of these modalities as well as the joint use of the two.Methods In this study,a total of 50 breast lesions in 37 patients proved by surgery and pathology were included.Before operation,all patients were underwent both ABVS and dynamic contrast-enhanced (DCE-MRI) examinations,and classified into groups according to BI-RADS classification.Then the effectiveness of the two examinations were contrasted,the image features on the two techniques were analyzed,and their differential diagnosis in benign and malignant breast lesions were compared.Results The sensitivity,specificity,accuracy,positive predictive value (PPV) and negative predictive value(NPV) of ABVS and MRI for the diagnosis of breast cancer were 91.67％ and 95.83％,88.46％ and 80.77％,90.00％ and 88.00％,88.00％ and 82.14％,92.00％ and 95.45％,respectively,and there was no statistical difference between ABVS and MRI(P ＞0.05);The sensitivity and specificity of the combination of the two were 99.65％ and 97.78％,respectively.The difference of the ABVS coronal features and MRI dynamic enhancement curve types between malignant breast lesions and the benign were statistically significant (P ＜ 0.05).Conclusions Both ABVS and MRI are effective to diagnose breast cancer well,while the combination of the two can improve the diagnosis more accurately.

Objective To explore the image performance of mucinous breast carcinoma( MBC) on automated breast volume scanner ( ABVS ) and its pathologic features ,for the purpose of improving the recognition of this disease on ABVS ,as well as diagnostic ability . Methods Retrospectively analyzed the sonogram and pathological data of 17 patients with 18 MBC lesions that included 9 PMBC ( pure mucinous breast carcinoma) and 9 MMBC( mixed mucinous breast carcinoma) ,all patients were examined by ABVS before operation and confirmed by pathology . Results Luminal A was the main molecular subtype of MBC ,as well as rarely lymph node metastases;The image of the MBC on ABVS mainly showed a round like or irregular mass ,isoechoic or slightly lower with posterior acoustic enhancement ,and clearly edge with microlobulated or angular ;While on the coronal plane ,it might presented unsmoothed contour ,retraction phenomenon and expansive growth pattern like a spherical nodular;The image characteristics of the PMBC and MMBC lesions on ABVS had no statistical difference( P > 0 .05) ,but the PMBC often performed isoechoic mass with clearly marge ,in contrast , the MMBC usually performed hypoechoic mass with indistinct and angular edge ,and the malignant image features on the coronal plane . Conclusions The three vertical sections of ABVS are beneficial to observe the morphological features of MBC completely ,which can help to identify it from the benign lesions ,reduce misdiagnosis ,and provide some guidance for MBC surgical treatment in the early stage .

Objective To compare the efficiencies of handheld ultrasound ,automated breast volume scanner ( ABVS) and breast specific gamma imaging (BSGI) in the diagnosis of breast cancer . Methods A retrospective review was performed in 200 women ( 210 breast lesions) underwent handheld ultrasound , ABVS and BSGI before surgery . The results were verified with histological examination . Results There was no obvious difference among the three methods in the sensitivity for the diagnosis of breast cancer( P >0 .05) . There was no difference of specificity between handheld ultrasound and ABVS ,BSGI( P = 0 .393 , 0 .139) . Compared with BSGI ,ABVS was an imaging modality with highest specificity for the diagnosis of breast cancer( P = 0 .021) ,and there was no difference between handheld ultrasound and ABVS ,BSGI ( P =0 .07 ,0 .29) . The areas under the ROC curve of handheld ultrasound ,ABVS and BSGI were 0 .855 ,0 .894 and 0 .818 ,respectively . The difference was obvious between ABVS and BSGI ( P = 0 .02) . Conclusions The diagnostic efficacy of ABVS in diagnosis of breast malignant lesions is similar to that of handheld ultrasound . BSGI has certain clinical value in the diagnosis of breast cancer ,and it is an effective supplement for breast cancer ultrasound examination .

Objective Mitochondrial DNA depletion syndrome is a rare autosomal recessive disorder characterized by complex genetic and clinical manifestations.This study aimed to investigate the clinical and laboratory features of a boy with mitochondrial encephalomyopathy caused by SUCLG1 mutation.Methods The clinical data and genetic test of a patient with mitochondrial DNA depletion syndrome were retrospectively analyzed.Result The proband presented with limb weakness at the 4th month after birth,and presented dystrophic appearance,muscular hypotonia,psychomotor retardation,failure to thrive,hearing impairment,scoliosis,thoracocyllosis and facial features at 9 months old.Laboratory tests showed blood lactic acid and pymvate increased,liver damage and abnormal myocardial enzymes.Plasma camitine ester profiling showed that amino acids decreased and C4-dicarboxylic-carnitine increased.Urinary organic acid analysis showed increased concentration of methylmalonic acid and its metabolites indicating methyl malonic aciduria.MRI showed bilateral T2 hyperintensities in bilateral caudate nuelei and lenticular and brain atrophy-like changes.Brainstem auditory evoked potential showed severe hearing loss.His development quotient was 35.Genetic sequencing of MUT,,MMAA,MMAB and other classic mitochondrial disease related genes of the proband revealed no mutation.Two heterozygous mutations,c.961C＞G and c.713T＞C,inherited from the phenotype of normal parents were detected in his SUCLG1 gene.The copy number of mitochondrial DNA was 244/cell in peripheral blood leukocytes,equivalent to 68.4％ of that in normal control.Conclusion In this study,an infant with muscular hypotonia,psychomotor retardation,deafness and slightly increased urine methyl malonic acid was diagnosed by genetic test.For patients with unexplained hypotonia,mental retardation,abnormal movements,hearing disorder together with increased blood pyruvic acid and lactic acid,mild methylmalonic acidemia and abnormal acylcarnitine,mitochondrial DNA depletion syndrome should be considered.Gene analysis is important for diagnosis and prenatal diagnosis of the next pregnancy.

Objective: To investigate the value of contrast-enhanced ultrasound(CEUS) in differential diagnosis of complex renal cysts and clear renal cell carcinoma with cystic change(CRCCC). Methods: The ultrasonographic datas of 82 lesions in 82 patients with complicated renal cysts or CRCCC confirmed by pathology were analyzed. The characteristics of conventional ultrasound and CEUS were observed and evaluated. The lesions were graded according to Bosniak classification criteria. Results: Pathological examination showed that 36 cases were complicated renal cysts and 46 cases were CRCCC. Routine ultrasound showed there were 9 cases (25.0%) with cystic masses and 27 cases (75.0%) with solid and cystic masses in complex renal cysts, of which 14 cases (38.9%) could detect color flow signals. In CRCCC, 2 cases (4.3%) were with cystic masses and 44 cases (95.7%) were with solid and cystic masses, of which 33 cases (75.0%) could detect color flow signals. CEUS showed that only 18 cases (50.0%) of the complex renal cysts showed enhancement of cystic wall or septum, with equal or low enhancement at the peak, 9 cases (50.0%) accompanied by decrease of renal cortex, 35 cases (97.2%) had thin and regular cystic wall, no enhancement of cystic wall in all lesions, and 33 cases (91.7%) had septal thickness less than 1 mm. Forty-five cases (97.8%) of CRCCC showed enhancement of cystic wall or septum, 40 cases (88.9%) showed equal or high enhancement at peak, 30 cases (66.7%) were faster than the decrease of renal cortex, 37 cases (80.4%) showed uneven thickness of cystic wall, 24 cases (52.2%) showed enhancement of cystic wall nodules, and 28 cases (60.9%) showed uneven thickness of septum. After CEUS, 33 cases (91.7%) of complex renal cysts were classified as grade Ⅰ and Ⅱ, while 42 cases (91.3%) of CRCCC were classified as grade Ⅲ and Ⅳ. Conclusions The CEUS manifestations of complex renal cysts are different from those of CRCCC. The application of Bosniak criteria in CEUS is helpful for the differential diagnosis of complex renal cysts and CRCCC.