Objective To investigate the correlation between vertebral artery dominance (VAD) and posterior circulation ischemic stroke (PCIS).Methods The consecutive patients with acute ischemic stroke hospitalized from November 2013 to October 2015 were collected.All patients underwent MRI and magnetic resonance angiography (MRA).The dominant vertebral artery was defined as having the larger diameter if left and right diameter difference ≥0.3 mm or the vertebral artery connected to the basilar artery in a more straight fashion if the diameter difference ＜ 0.3 mm.They were divided into either an anterior circulation ischemia stroke (ACIS) group or a PCIS group according to the classification criteria of Oxfordshire Community Stroke Project (OCSP).A multivariate logistic regression analysis was performed to investigate the correlation between VAD and PCIS.Results A total of 226 patients withacute ischemic stroke were enrolled,including 172 patients (76.1％) in the ACIS group and 54 (23.9％) in the PCIS group.Fifty-four patients (23.9％) had VAD,including 38 (70.3％) on the left and 16 (29.7％) on the right.The proportion of the patients with VAD in the PCIS group was significantly higher than that in the ACIS group (55.6％ vs.14.0％;x2 =39.115,P ＜ 0.001).Multivariate logistic regression analysis showed that VAD was an independent risk factor for patients occurring PCIS (odds ratio,13.60,95％ confidence interval 6.90-27.01;P＜0.001).Conclusions VAD is closely associated with the occurrence of PCIS,and it is an independent risk factor for PCIS.

Objective To obtain highly purified botulinum neurotoxin A light chain(BoNT-ALC) protein in E.coli by genetic engineering and multi-step purifications, and identify its metalloproteases activity.Methods The full-length of BoNT-ALC was cloned from BoNT A by PCR and inserted into plasmid pET-22b.Then pET-22b-ALC was transformed into E.coli BL21( DE3) strains and induced by IPTG.The protein was purified by Ni-NTA sepharose,anion exchange column and gel filtration.The enzymatic activity of the protein was identified by SNAP-25.Results and Conclusion A highly purified and homogeneous protein is obtained, which shows good enzymatic activity.

Objective To synthesize N-(4-fluorophenyl)-N-(4-phenoxyphenyl) cyclopropane-1,1-dicarboxamide (NFNPDB) as small molecular c-Met kinase inhibitor analogue.Methods N-( 4-fluorophenyl )-N-( 4-phenoxyphenyl ) cyclopropane-1, 1-dicarboxamide was synthesized by nucleophilicsubstitution, amidation, etherification, reduction and condensation from diethyl malonate.Results The total yield of target compound was 3.79%, its structure was confirmed by 1 H-NMR.Conclusion The synthesis method of NFNPDB in our research can be easily operated with lost cost and short direction, which lays the foundation for designing the synthetic process of newly small molecular c-Met kinase inhibitor.

Objective To design and synthesize compounds with protein tyrosine kinase(PTK)inhibitory activity with L029 as the lead compound. Methods L029 derivatives were designed and synthesized from L029 by reduction and/or substitution with the 3-dimethylamino-1-propyl,methyl acetate,methyl propionate in its active H and other sites. PTK activity was measured by enzyme-linked immunosorbent assay(ELISA). The inhibitory rate was calculated to screen out the compounds with PTK inhibitory activity. Re-sults Five target compounds were synthesized and their structures were confirmed by 1H NMR and MS. Three compounds T2,T3 and T5 were screened out with strong PTK inhibitory activity. Conclusion The synthetic routes of the target compounds are simple with mild reaction condition,and 3 compounds show strong inhibitory activity by ELISA. These results can provide reference for the further design and synthesis of this kind of molecules.

Objective To design and synthesize novel 2-indolone derivatives as the c-Met kinase inhibitors. Methods With c-Met kinase inhibitor SU11274 as lead compound,a series of 2-indolone derivatives were designed according to the concept of bioiso-sterism. Then the target compounds(10a-10r)were synthesized from 2-indolone through 5-chlorosulfonation with chlorosulfonic acid, sulfonamidation with intermediate 3,condensation with 6a-6h,7a-7h and 4a-4b,respectively. Their inhibitory activity against c-Met and proliferation of MCF-7 cells were evaluated. Results and Conclusion The designed compounds were successfully prepared and their structures were confirmed by 1H NMR and ESI-MS. Some compounds had certain inhibitory activity against c-Met and prolif-eration of MCF-7 cells. An initial structure-activity relationship analysis of these compounds was performed to provide useful informa-tion for further optimization of their structures.

Objective To observe the clinical characteristics ofretinoblastoma (RB) in Southwest China.Methods A retrospective clinical study.From January 2010 to December 2017,66 RB patients diagnosed in Ophthalmology Department of West China Hospital of Sichuan University were included in the study.All the patients underwent ocular B-ultrasound,orbital CT or MRI examination.Ten patients underwent RetCam examination at the same time.Twenty-nine patients were diagnosed by histopathological examination,and 37 patients were diagnosed by clinical symptoms and imaging examination.According to whether the tumor invaded the orbit and optic nerve,it could be divided into extraocular stage and intraocular stage.Intraocular tumors were divided into A-E stages according to the international intraocular RB classification.Treatments were performed according to different stages.The general information,age at diagnosis,course of diseases (the time between onset symptoms and diagnosis),causes of visiting a doctor,classification,treatment methods and eyeball preservation rate were retrospectively analyzed.Results Patients all came from Southwest China (56 patients from Sichuan Province,2 patients from Yunnan Province,2 patients from Guizhou Province,and 6 patients from Tibet).The permanent residence were identified in 43 patients,including 27 patients (62.8％) from rural areas.There were 38 males (57.6％);50 unilateral tumors (75.8％) and 16 bilateral tumors (24.2％);51 firstvisiting patients (77.3％) and 15 re-visiting patients (22.7％).The average diagnostic age of first-visiting patients was 20.9 ± 14.4 months,with 23.2 ± 14.7 and 11.2 ± 7.6 months for unilateral and bilateral tumors,respectively.There were 41 patients had definite course and causes,of whom the average course was 90.6± 115.2 days.The most common cause was leucocoria in 32 patients (62.7％),followed by redness and swelling in 4 patients (9.8％),and other causes in 5 patients (12.2％).Among the 15 re-visiting patients,the average diagnostic age was 63.6± 46.8 months,the average course was 32.8 ± 45.5 months.Recurrence was occurred in 5 patients (33.3％),leucocoria in 4 patients (26.7％),postoperative complication in 3 patients (20.0％),protrusion in 2 patients (13.3％) and redness in 1 (6.7％) patient,respectively.Fifty out of 82 eyes were admitted to hospital,including 37 eyes of first-visiting patients and 13 eyes of re-visiting patients.Among 37 first-visiting eyes,there were 5 eyes (13.5％) in stage A-C,26 eyes (70.3％) in stage D-E,6 eyes (16.2％) in extraocular stage.Five eyes in stage A-C were treated with laser photocoagulation and (or) cryotherapy combined with systemic chemotherapy.Four eyes in stage D were treated with intraocular arterial chemotherapy.Nineteen eyes (51.3％) were performed with enucleation,2 eyes (5.4％) with evisceration and 7 eyes (18.9％) abandoned treatment.Among 13 re-visiting eyes,6 eyes (46.2％,with 5 eyes of recurrence) had been enucleated before,4 eyes (30.8％) were in extraocular stage and 3 eyes (23.1％) in stage D-E.Five eyes (38.5％) were treated with evisceration,4 eyes (30.8％) with enucleation,1 eye with oculoplastic surgery and 3 eyes (23.1％) abandoned treatment.The rate of eye preservation was 18.0％,29.0％ for intraocular stage and 0％ for extraocular stage,respectively.Conclusion RB patients in Southwest China have a longer course between onset symptoms and diagnosis,more advanced classification and lower rate of eye preservation.

OBJECTIVE:To establish the method for simultaneous determination of the content of berberine hydrochloride, baicalin and osthole in Jinchan zhiyang capsules. METHODS:HPLC method was adopted. The determination was performed in Hypersil BDS C18 column with mobile phase consisted of methanol-acetonitrile-0.1%phosphoric acid-three triethylamine(50∶30∶19∶1, V/V/V/V) at the flow rate of 1.0 mL/min. The detection wavelengths were set at 265 nm (berberine hydrochloride),280 nm (baicalin)and 322 nm(osthole). The column temperature was set at 30 ℃,and sample size was 10 μL. RESULTS:The linear range of berberine hydrochloride,baicalin and osthole were 80-800 ng(r＝0.999 8),60-600 ng(r＝0.999 9),60-600 ng(r＝0.999 6),respectively. RSDs of precision,stability and reproducibility tests were all lower than 2.0%. The limits of quantitation were 80,60,60 ng,respectively,and the limits of detection were 24,20,20 ng,respectively. The recovery rates were 97.4%-98.3%(RSD＝0.33%,n＝6),98.4%-99.6%(RSD＝0.42%,n＝6)and 96.9%-99.0%(RSD＝0.92%,n＝6),respectively. RSDs of durability tests were all lower than 1.2%. CONCLUSIONS:The method is simple, accurate, precise, stable, reproducible and durable. It can be used for simultaneous determination of berberine hydrochloride,baicalin and osthole in Jinchan zhiyang capsules.

The analysis on regularity of comparability among famous physician's prescriptions for treating chest pain since the Han Dynasty will be helpful to treat chest pain and develop new herbs.The Chinese Medicine Auxiliary System (V2.5) was used to analysis the regularity of comparability by inputting the most famous 101 prescriptions for the treatment of chest pain from the Han Dynasty to Qing Dynasty.The results showed that the most common single drugs were cassia twig,40 times (39.6％).The most common couplet medicines were licorice and poria cocos,21 times (20.8％).The most common triangle medicines were ginger,pinellia,and cassia twig,13 times (12.9％).The most common drug combination based on association rules was the combination of cassia twig,peucedani radix→ginger (confidence level of 0.909 1).The core drugs based on complex network was cassia twig,licorice,and etc.New prescription combinations based on the entropy method were 11 new prescriptions including allium,cassia twig,poria,and almonds.It was concluded that there were regularity of comparability in ancient prescriptions for treating chest pain.Approaching and developing medicine for the treatment of chest pain should be from the following 6 points.The priority choice of single drug was cassia twig,and etc.The priority choice of couplet medicines was licorice and poria cocos,etc.The priority choice of triangle medicines was ginger,pinellia,cassia twig,and etc.The combination of high correlation should be chosen in treating chest pain,such as cassia twig,peucedani radix→ginger,and etc.The core drugs are necessary.In the warming yang method,cassia twig is the core drug and ginger is the auxiliary drug,and etc.New prescription combination,such as allium,cassia twig,poria,almonds,and etc.should be applied.

Objective To explore the influence of rs1360780 T risk allele of FK506-binding protein 5 (FKBP5) gene on the brain function under resting-state and its association with clinical symptoms as well as immune function in patients with major depressive disorder (MDD).Methods Totally 147 MDD patients and 61 gender-,age-,and education-matched healthy controls were scanned with 3.0T MRI Scanner and genotyped.The peripheral serum immunoglobulin and complement were measured.The main effect of the disease,the genotype and their interaction effects were analyzed using regional homogeneity (ReHo) by two-way ANOVA.Abnormal brain activity was identified in T risk allele carriers of rs1360780 and non-risk CC individuals in MDD using post hoc analyses.Correlation analyses were performed between ReHo values of significant brain regions and the total score,five-factor scores of Hamilton rating scale for depression (HAMD-17),serum levels of immunoglobulin and plasma complement component in MDD patients.Results (1) The results of 2x 2 ANOVA showed the interaction effects located in the left opercular part of inferior frontal gyrus (MNI:x,y,z =-42,6,9;F=10.83),right opercular part of inferior frontal gyrus (MNI:x,y,z =30,6,33;F=15.05),left medial superior frontal gyrus (MNI:x,y,z=-9,54,0;F=9.17) and left pallidum (MNI:x,y,z =-12,6,-6;F=11.37) (Alphasim corrected,P＜ 0.05).(2) In post-hoc analyses for the main effect of genotype,T+ carriers with MDD showed increased ReHo values in the right opercular part of inferior frontal gyrus (MNI:x,y,z=60,12,6;t=2.88) compared with CC carriers;for the effect of diseaseby-genotype interaction,T+ carriers with MDD showed increased ReHo values in the right opercular part of inferior frontal gyrus (MNI:x,y,z=30,6,33;t=2.96) and decreased ReHo values in the left orbital part of inferior frontal gyrus (MNI:x,y,z =-21,9,-18;t =-3.21) (Alphasim corrected,P＜ 0.05) in contrast to CC carriers.(3)Pearson's correlation showed that the average ReHo values of the right opercular part of inferior frontal gyrus negatively correlated with the content of immunoglobulin G (r=-0.528,P=O.0016,Bonferroni corrected) and positively correlated with anxiety/somatization factor score (r=0.421,P＜0.001,Bonferroni corrected) in T + carrìers with MDD.Conclusion The results of this study suggest that rs1360780 T-risk allele of FKBP5 gene is involved in the changes of local neural activity in the right opercular part of inferior frontal gyrus of depressed patients and could potentially indicate a neuropathological mechanism of anxiety somatic symptoms and immune dysfunction in depression.

This study investigates the metabolic regulatory effects of exogenous lactate on obesity mice induced by high-fat diet.We established obesity and metabolic disorder C57 mice model using a synthetic high-fat forage containing 60% fat.Some mice were fed with high-fat diet for 4 weeks to establish the model, being given 500 mg/(kg?d) lactate with ip for 4 weeks at the same time; the others were fed with high-fat diet for 8 weeks to establish the model, being given 500 mg/(kg?d) lactate 4 weeks after 4 weeks of modeling.During the trial period, the change of body weight and food intake, as well as serum glucose, lactate, triglycerides, insulin, and liver glycogen levels of both groups of mice were measured.Oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were used to assess glucose metabolism and insulin resistance in the body.At the end of the experiment, adipose tissue was dissected for weighing and histopathological examination.The expression of lipid synthesis and lipolysis genes in adipose tissue was detected by real-time PCR.The results showed that: (1) in the 4-week preventive medication trial, lactate had no significant effect on the body weight of normal and high-fat diet (HFD) mice, yet it increased the subcutaneous fat/visceral fat weight ratio; lactate could significantly reduce fasting blood glucose and liver glycogen levels in HFD mice while increasing blood lactate levels, significantly improving impaired glucose tolerance in HFD mice; lactate could improve the size and arrangement of adipocytes in the HFD group while significantly down-regulating the expression of fatty acid synthesis and lipolysis genes in adipose tissue; (2) in the 8-week treatment, both routes of lactate administration could partially reduce body weight in HFD group mice and reduce food intake, with the improvement trend for fat weight; both routes of lactate administration could significantly reduce fasting blood glucose levels in HFD mice, while significantly improving glucose and insulin tolerance, with some improvement of fasting insulin levels and insulin resistance index; both routes of lactate administration showed different degrees of improvement effect on adipocyte morphology in obese mice while significantly down-regulating lipolysis gene expression in adipose tissue.Therefore, for high-fat diet-induced obese mice with metabolic imbalance, exogenous lactate can stimulate glucose metabolism, inhibit adipose tissue lipolysis, and prevent adipocyte hypertrophy, thereby improving glucose tolerance and insulin sensitivity and reducing sugar-lipid metabolic disorder.