ObjectiveTo explore the regulation of hypothalamic-pituitary-gonadal （HPG） axis by modified Erxian decoction in rats with perimenopausal syndrome （PMS） and to further analyze the expression of proteins related to the silent information regulator 1 （SIRT1）/hypothalamic kisspeptin （Kisspeptin）/gonadotropin-releasing hormone （GnRH） signaling pathway in the arcuate nucleus region （ARC） of the hypothalamus， so as to reveal the potential target of action and molecular biological mechanism of modified Erxian decoction for the treatment of perimenopausal syndrome. MethodsAn animal model was established via the incomplete castration method， with successful modeling confirmed by the exfoliated cervical cell smear method. The 48 rats were divided into six groups based on the randomization principle after successful modeling， including a sham operation group， a model group， an estradiol valerate group （0.09 mg∙kg^-1∙d^-1）， high-， medium-， and low-dose modified Erxian decoction groups （7.614， 3.807，1.903 5 g∙kg^-1∙d^-1）， with 8 rats in each group. The estradiol valerate group and the high-， medium- and low-dose modified Erxian decoction groups were continuously administered by gavage for 28 days， and the indicators were detected 24 hours after the last administration. Body weights and uterine indices were measured. The pathological changes of the uterus were observed by hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was performed to measure the levels of estradiol （E₂）， follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and gonadotropin-releasing hormone （GnRH）. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to determine the expression levels of SIRT1， Kisspeptin， kisspeptin receptor （GPR54）， and GnRH in the ARC region of the hypothalamus and gonadotropin-releasing hormone receptor （GnRH-R） in pituitary. ResultsCompared with the sham operation group， rats in the model group had a significantly increased body weight （P0.01）， reduced wet weight and index of uterus （P0.01）， endometrial thinning or atrophy， glandular atrophy， and a decreasing number of glands. Additionally， serum levels of E₂ and the expression of SIRT1 in the ARC region of the hypothalamus significantly decreased （P0.01）. Serum levels of FSH， LH， and GnRH， the expression of Kisspeptin， GPR54， and GnRH in the ARC region of the hypothalamus， and GnRH-R in pituitary significantly increased （P0.01）. Compared with the model group， the estradiol valerate group and the high-， medium-dose modified Erxian decoction groups had significantly reduced body weight， serum levels of FSH， LH， and GnRH， and expression of Kisspeptin， GPR54， and GnRH in the ARC region of the hypothalamus and GnRH-R in pituitary （P0.05， P0.01） and significantly increased wet weight and index of uterus， serum level of E₂， and expression of SIRT1 in the ARC region of the hypothalamus （P0.05， P0.01）. In addition， they showed thickened endometrium， increased number of endometrial glands， and improved glandular atrophy. ConclusionModified Erxian decoction regulates the function of the HPG axis through multi-targets， and its mechanism of action may be related to the up-regulation of the expression of SIRT1 in the ARC region of the hypothalamus， the inhibition of the over-activation of the Kisspeptin/GnRH signaling pathway， the regulation of the expression of GnRH-R in the pituitary， the restoration of secretion balance of gonadotropins， and the elevation of the estrogen level. This study provides an experimental basis for the interpretation of the scientific connotation of modified Erxian decoction in the treatment of perimenopausal syndrome and a theoretical reference for the development of a novel therapeutic strategy based on the SIRT1/Kisspeptin/GnRH pathway.

OBJECTIVE:To provide reference for drug consultation of Chinese patent medicine(CPM)in pregnancy. METH-ODS:Package inserts of CPM in our hospital during Jan.-Jun. 2016 were collected. Referring to the prohibited,contraindicated and caution materials and decoction pieces in Chinese Pharmacopoeia(part 1,2015 edition),based onnoteitem in Chinese Pharma-copoeia and Clinical Application Guidelines(2010 edition),problems existing in pregnancy contraindication labeling of package in-serts were compared and analyzed. RESULTS:There were 99 kinds of prohibited,contraindicated and caution materials and decoc-tion pieces in Chinese Pharmacopoeia. There were 210 package inserts of CPM except for the special medicine for children,in which 32 contained prohibited materials,61 contained caution materials,only 21 were in line with the contained materials. Among the package inserts of 93 CPM containing prohibited or caution materials,27 were included in Chinese Pharmacopoeia,13 in Clini-cal Application Guidelines only,17 in both,but only 6 had the same contraindication labeling. Among the package inserts of 32 CPM containing prohibited materials,6 were explicitly labeled prohibited,17 labeled contraindicated or caution,and 9 labeled none. Among the package inserts of 61 CPM containing caution materials,29 were labeled prohibited or contraindicated,15 la-beled caution,and 17 labeled none. Among the package inserts of 117 CPM containing no prohibited,contraindicated or caution materials,8 were labeled contraindicated in pregnancy,and 18 labeled prohibited in pregnancy. CONCLUSIONS:The pregnancy contraindications of most CPM are not normative,showing poor consistency with Chinese Pharmacopoeia or Clinical Application Guidelines. Except for providing drug consultation by complying with Chinese Pharmacopoeia,Clinical Application Guidelines and package insert,pharmacists can judge the CPM without labeled pregnancy contraindication by analyzing its classification of con-tained materials. Using TCM does not indicate safety drug use,in addition,some CPM contain western medicine ingredients. There-fore,pharmacists should conduct medication education for patients who used CPM in pregnancy. Considering the new and severe adverse reactions of TCM injections are more,its adverse reactions exist unpredictability,so that pregnant patients should be sug-gested to avoid using TCM injections by pharmacists.

Objective To observe the changes of invasion and migration patterns and integrin expression of malignant glioma cells when Rac and Rho pathways are suppressed,respectively,in 3D hydrogel.Methods Liposome mediated pCMVLifeAct-TagGFP2 plasmids were transfected into glioma U87 cells,and then,these cells were divided into NSC23766 treatment group,Y-27632 treatment group,NSC23766 and Y-27632 combined treatment group,and control group.The three treatment groups were added NSC23766 (100 nmol/mL),Y-27632 (10 nmol/mL),100 nmol/mL NSC23766 and 10 nmol/mL Y-27632,respectively;the cells in the control group were added the same amount of medium.Cells were cultured in hydrogel;the composition of round cells,spindle cells and the mesenchymal and amoeboid cell movement transition were observed under confocal microscopy.The hydrogels of each group were infused into the microslide,and the cell chemotaxis effect were recorded and the cell movement velocities and distances were calculated in the living cell workstation.Immunofluorescence was used to observe the alternation ofintegrin expression.Results U87 cells cultured in 3D hydrogel exhibited spindle-like and round-like shapes,corresponding to mesenchymal and amoeboid cell movement.As compared with that in the control group,the proportion of round cells in the NSC23766 treatment group was significantly higher,and that of spindle cells in the Y-27632 treatment group was significantly higher (P＜0.05).The conversion rate ofmesenchymal-amoeboid transition was 50.0％ in NSC23766 treatment group and amoeboid mesenchymal transition was 42.8％ in Y-27632 treatment group as compared with that in the control group,with significant differences (P＜0.05).The velocity and distance of cells cultured in 3D hydrogel decreased orderly in NSC23766 treatment group,control group,Y-27632 treatment group and combined treatment group in chemotaxis test.The immunofluorescence test showed that integrin expression in the Y-27632 treatment group was significantly higher than that in the other three groups,and that in the control group was statistically higher than that in the NSC23766 treatment group and combined treatment group (P＜0.05).Conclusions 3D hydrogel can be used as a favorable substrate for cell culture.The combination targeted inhabitation of Rac 1 and RohA pathways provides theoretical basis for anti-invasion treatment against glioma.

Objective To investigate the inhibitory effect of a disintegrin and metalloprotease 12 silenced by shR?NA on self-renewal capacity of CD133 positive giloma cells. Methods The shRNA recombinant lentivirus aimed at si?lencing ADAM12 was prepared. Human glioma cells U87 were employed in this study and assigned into three groups:shRNA-ADAM12, shRNA-NCandshRNA-C. ADAM12 expression was detected at mRNA and protein level using Re?al-time quantitative-PCR and western bloting, respectively. U87 cells were cultured with stem cell culture medium, to obtain cell sphere formation in which CD133 positive glioma cells were enriched. Immunofluorescence was employed to detect the expression of ADAM12 and CD133 in cell spheres and U87 cells; Self-renewal was tested by using tumor sphere formation assay. Molecular markers for differentiated or undifferentiated cells (CD133,GFAP and Tuj1) were de?tected at protein using western blotting. Western blotting was employed to test protein expression of HES1. Results AD?AM12 shRNA significantly down-regulated the mRNA and protein expression levels of ADAM12. Compared with shRNA–C group, the relative expression levels of mRNA in shRNA-ADAM12 group and shRNA-NC group were 0.22 ± 0.03 and 0.98 ± 0.06 (F=425.37,P<0.01). The relative expression levels of protein in shRNA-ADAM12 group, shRNA-NC group and shRNA-C group were 28.72%±2.36%, 69.21%±3.92%and 69.04%±3.57%, respectively (F=145.42,P<0.01). Immunofluorescence staining showed that expression levels of ADAM12 and CD133 in cell spheres were significantly higher than those in normal cells. The number of spheres in three groups were 45.5±2.3、104.2±5.8 and 109.6±6.2, tumor sphere formation ability of shRNA-ADAM12 group was lower than that of shRNA-NC group and shRNA-C group (F=147.03,P<0.01). Compared with the shRNA-NC group and shRNA-C group, the protain expression of GFAP and Tuj1 were increased up to 166% and 146% (P<0.01) whereas the protein expression levels of CD133 and HES1 were down-regulated by 54% and 50% (P<0.01). Conclusion Knockdown of ADAM12 may suppress self-renewal ability of CD133 positive glioma cells by inhibiting the Notch pathway activity.

Background and purpose: With characteristic but non-specific features, subsolid pulmonary nodules (SSPN) is closely associated with early lung cancer. This study aimed to estimate the imaging value of SSPN in stageⅠA lung cancer, and summarized the radiological features of various SSPNs, retrospectively. Methods:The clinical data and imaging data of 405 patients with solitary pulmonary nodules (SPNs) from Apr. 2008 to Apr. 2014 at Fudan University Shanghai Cancer Center were collected. According to ground-glass opacity (GGO) proportion, SPNs were divided into 3 groups:pure ground-glass opacity (pGGO), mixed ground-glass opacity (mGGO) and solid nodule (SN). The malignant ratios were calculated based on the postoperatively pathological results. Besides, SSPNs were classiifed into stageⅠA lung cancer group and benign lesions group aiming at identifying the differentiating computed tomography (CT) features. Results:Of the enrolled 405 SPN patients, there were 367 SSPNs (including 124 pGGOs and 243 mGGOs) whose incidence in stageⅠA lung cancer group was signiifcantly higher than those in benign group [95.9%(257/268) vs 80.3%(110/137), P<0.001]. The total malignant ratio of SSPN was 70.0%(257/367), mGGO had a higher malignant ratio (72.0%) than those of pGGO (66.1%) and SN (28.9%). The malignant SSPNs were frequently detected in upper lobe of middle-aged women with a higher incidence of irregular edge, spiculation, lobulation and pleural retraction than benign group (P<0.05). Conclusion:SSPN is one of the signiifcantly malignant indicators, and mGGO has the highest malignant tendency. Senility, female, irregular edge, spiculation, lobulation, pleural retraction and pulmonary upper lobe distribution are demonstrated the signiifcant discriminators from benign lesions.

Objective To analyze the etiology and clinical characteristics of infectious mononucleosis-like syndrome (IMLS).Methods Eighty-seven children with IMLS in a hospital from January 2006 to September 2013 were per-formed pathogenic detection,then clinical features were summarized and analyzed.Results The top 5 pathogens in IMLS were Mycoplasma pneumoniae (MP,n=20 ),cytomegalovirus (CMV,n=13),simplex herpes virus(HSV, n=11),Chlamydia (CP,n=11),and parvovirus B19 (Hpv B19,n=9 ),clinical manifestations of all kinds of dis-eases were similar,but the occurrence rates were slightly different.MP infection were mainly fever,hepatospleno-megaly,and lymphadenopathy,and most were associated with respiratory complications(including laryngitis,bron-chitis,and pneumonia),CMV infection were also showed fever and hepatosplenomegaly,but the latter was more ob-vious;rubella patients didn’t appear skin rash,but the other symptoms were obvious.Conclusion Etiologies of in-fectious mononucleosis-like syndrome are varied,MP infection is most common,the next is CMV.Pathogens should be ascertained to provide theoretical basis of treatment.

Objective To investigate the clinical manifestations, angiographic features and clinical significance of kinking of extracranial internal carotid artery (ICA). Methods The clinical and radiological data of 21 patients with kinking of extracranial ICA were retrospectively reviewed in our hospital from April 2003 to July 2007. Fisher exact test was performed. Results Of the 21 patients, 7 hod no clinical symptoms, the other 14 showed manifestations of cerebral iachemia with varying degree. One of the characteristic clinical manifestations that neck rotation or specific positions of head and neck might induce the occurrence of clinical symptoms was found in 5 cases. The whole-brain coverage DSA accurately showed the location of kinking of extracranial ICA and the degree of vascular stenosis. In patients with α < 66%, 80% > α≥ 66% and α≥ 80%, clinical symptoms were found in 3 out of 5,7 out of 10 and 4 out of 6 patients, respectively. Fisher exact test revealed that the positive rates of clinical symptoms in three groups had no significant difference (P > 0. 05). Conclusion Kinking of extracranial ICA is a frequent vascular morphologic variation, and it is also a kind of potential disease. The whole-brain coverage DSA is a relatively reliable method to detect this variation.

Objective To evaluate the short-term outcome of local intraarterial thrombolysis in patients with acute ischemic stroke of the anterior circulation. Methods 24 patients with acute ischemic stroke of the anterior cir-culation within 8 hours were treated by local intraarterial thrombolysis. Arterial recanalization was divided into total, partial and occlusive respectively according to angiography. Evaluation of clinical outcome was performed on the 30th day after thrombolysis,and was classified as good for Modified Rankin Scale (MRS) scores of 0 to Ⅲ and poor for MRS scores of Ⅳ to Ⅵ. Results Total recanalization was obtained in 54.2 % of patients, partial recanalization in 25.0%. Clinical outcome was good in 15 patients (62.5%). Cerebral hemorrhage occurred in 4 patients (16.7%). Four patients died (16.7%). Conclusion Local intraarterial thrombolysis is an effective method for treatment of a-cute iachemic stroke of the anterior circulation. It needs further practice and long-term follow-up study on safety and long-term efficacy.