OBJECTIVE Topreparealipidderivativeofgemcitabine(Gem)anditspolymericmi-celles to overcome the disadvantages of Gem.METHODS N-benzyl-3′-acetyl-gemcitabine(BAG)was synthesized.A BAG-loaded poloxamer polymeric micelle (BAG∶poloxamer 188 =10∶1 ,mol/mol)was prepared using an injection method.The micelles were characterized with a laser particle size and elec-tric charge instru ment and negatively-stained trans mission electron microscopy.Hu man breast cancer cells MCF-7 were cultured with Gem or BAG polymeric micelles of 5,10,20,30,50,70,90 μmol·L-1 for 24,48 and 72 h,respectively.The inhibitory rate of cells was measured with an MTT method.The MCF-7 cytotoxicity of BAG polymeric micelles was investigated.A pharmacodynamic study was per-formed on the mice bearing mouse hepatocellular cancer cells H22.Intravenous (iv)and oral (ig)ad-ministration was used at the dose of Ge m 40 mg·kg -1 or BAG polymeric micelles 62 mg·kg -1 .The mice were administered on the 1 st,4th and 7th day and sacrificed on the 8th day.Tumor inhibitory rates were measured.RESULTS TheBAGstructurewasidentifiedbythinlayerchromatograph,1Hand13C NMR,infrared ray chromatograph and mass spectrum.The appearance of BAG micelles was a slightly blue suspension.The micelles were spheres according to the electron microscopic observation.Their size was 62.82 nm and the zeta potential was -18.8 mV.The half inhibition concentration (IC50)of Gem and BAG polymeric micelles was 40.6 and 90.0 μmol·L-1 ,5.0 and 14.9 μmol·L-1 ,5.0 and 1 3.6 μmol·L-1 at 24,48 and 72 h,respectively according to the MTT results.According to the in vivo results,compared with the tumor model group,Gem (ig),Gem (iv)and BAG polymeric micelles (iv and ig)had significant effect on the tumor weight of H22 cell xenograft mice (P<0.01 ).As for anti-tumor efficiency,BAG polymeric micelles (ig)were better than Gem (ig)(P<0.05);BAG polymeric micelles (iv)were better than BAG polymeric micelles (ig)(P<0.05),and BAG polymeric micelles (iv)were almostequaltoGem(iv).CONCLUSION ThelipidderivativeofGemcanbeloadedinthepoloxamer 1 88 polymeric micelles.BAG polymeric micelles show in vitro MCF-7 cell inhibition and in vivo inhibition of mouse H22 xerografts;iv or ig.BAG polymeric micelles (ig)show better anti-tumor effect than Gem (ig),indicating that BAG polymeric micelles are a promising novel anti-tumor oral preparation.

Objective To explore the role of pregabalin on the expression of c-fos in spinal dorsal horn of the rat with neuropathic pain.Methods Thirty Wister rats (male) were divided into shamoperated group,model group and pregabalin group,with 10 cases in each group.The effect of the pregabalin on the heat pain threshold and expression of c-fos in spinal dorsal horn of the rat with neuropathic pain were observed.Results The heat pain threshold in model group at 3rd,4th,5th,6th,7th,10th and 14th day after operation was significantly lower than that in sham-operated group and pregabalin group at same time (P ＜ 0.05).The heat pain threshold in pregabalin group was lower than that in sham-operated group from 2nd day after operation,but there was no significant difference (P ＞0.05).At the 14th day after operation,the number of Fos-like-immunoreactivity (FLI) positive cells in sham-operated group,model group and pregabalin group was (16.4 ± 0.6),(66.7 ± 3.3) and (22.8 ± 1.5)cases,and the number of FLI positive cells in model group was significantly higher than that in shamoperated group and pregabalin group (P ＜ 0.05).Conclusions Pregabalin has analgesic activity on rat with neuropathic pain.Pregabalin activates spinal cord glial cells raisedby the injured peripheral nerve and infection,and also reduces the noxious stimulation of afferent pain to spinal dorsal horn neurons.

Objective To investigate whether sex,age-of-onset,education and asymmetry affect non-motor symptoms (NMS)in Parkinson disease,and to analyze the relationship between motor symptoms and NMS in Parkinson's disease.Methods The detailed clinical information of 157 patients with idiopathic Parkinson's disease(PD)was recorded and followed up.The data was calculated with SPSS statistic software.Sex had an impact on sleeping disorder (P＜ 0.05).Sleep disorder in female was more prominent.Cognitive disorder was affected by age-of-onset and education duration.The pain and sensory disorder were affected by age-of-onset (P ＜ 0.05).Differences in the effects of asymmetry on NMS were not statistically significant (P＞ 0.05).The higher the scores of postural instability and gait difficulty (PIGD)were,the lower the Mini-Mental State Examination (MMSE)score was(β=-1.837,P =0.004).The higher the tremor score was,the higher the Hamilton Depression Scale(HAMD) score was(β=3.460,P =0.001).The higher the rigidity akinesia score was,the higher the autonomic dysfunction score was(β=0.104,P=0.006).Conclusions The non-motor symptoms of Parkinson's disease are affected by the age,sex and cultural level.Symmetryor-not does not affect Parkinson's disease.Non-motor symptoms and motor symptoms are closely linked.The encountered posture and gait abnormalities of patients should trigger physician alerts to focus on patients' cognitive function.The encountered tremor of patients should trigger physician alerts to focus on their emotional changes.Facing to the patient with rigidity and less moving,physician should alert to the occurrence of autonomic symptoms.

Group A β-hemolytic streptococcus (GAS),namely Streptococcus pyogenes,is one of the most im-portant human pathogen.GAS can cause skin and mucous membrane superficial infectious diseases,life -threatening invasive disease,toxin -mediated diseases and immune -related diseases.Antibiotic is an effective mean to control GAS infection.The β-lactam antibiotics remain the first -choice treatment for GAS infection and the macrolides are often recommended as a replacement therapy for β-lactam antibiotics allergic patients or a means to blocking GAS exotoxin product.But with the widespread use of macrolides autibiotics,macrolide -resistant GAS spread in the world. This paper will elaborate the situation of macrolide -resistant clones.

Objective To investigate the correlation between Framingham stroke risk profile(FSRP) and vascular cognitive impairment in stroke-free patients with cerebrovascular risk factors.Methods One hundred and eighty-four stroke-free subjects,selected from Zhejiang hospital,were divided into low risk group (56 subjects),moderate risk group (70 subjects) and high risk group (58 subjects) according to their FSRP score,and their cognitive function including memory ability,attention,executive function and language ability were assessed by Montreal cognitive assessment (MoCA),auditory verbal learning test (AVLT),digit symbol test,trail making test(TMT),digit span and verbal fluency test.Results The total MoCA scores which were (7.2±4.6),(13.8±3.9),(29.6± 12.7) respectively,AVLT-delay recall scores which were(8.2± 1.6),(6.7± 1.4),(5.9± 1.5) respectively,and digit symbol test score which were(34.7±9.3),(32.6± 16.4),(29.7± 13.6) respectively in low,intermediate and high risk groups,decreased with the increasing risk of stroke(P＜0.05).The elapsed time in TMT-B which were (115.2 ±36.9) s,(147.6±44.8) s,(173.9±58.5) s respectively in low,intermediate and high risk groups,prolonged with the increasing risk of stroke (P＜0.05).FSRP was associated with cognitive function,but inversely related to MoCA,AVLT-delay recall,digit symbol test,TMT-B and digit span fall back (P＜0.05),but positively related to consuming time in TMT-B (P＜ 0.05).Multivariate regression analysis showed that advanced age,hypertension,diabetes and smoking were the risk factors for vascular cognitive impairment(P＜0.05).Conclusion Advanced age,smoking,hypertension and diabetes are the most important in vascular risk factors for cognitive impairment.Vascular risk factors can damage cognitive function with the increased risk of stroke,among which delayed recall and executive function are the main affected cognitive area.

This study aims to analyze and compare the effect of cell wall-broken decoction pieces, conventional decoction pieces and conventional powder of Rhodiolae Crenulatae Radix et Rhizoma on the intestinal flora of normal mice. The conventional bacterial culture and PCR-DGGE (polymerase chain reaction-denaturing gradient gel electrophoresis) were adopted for the mice after the oral administration for 14 days. According to the bacterial culture results, the 1/8 dose cell wall-broken decoction pieces group showed fewer Enterococcus and Escherichia coli bacillus but more Lactobacillus and Bifidobacterium than the conventional decoction pieces group and the traditional powder group (P <0.05). Meanwhile, on the basis of the PCR-DGGE results, the 1/8 dose cell wall-broken decoction pieces group revealed the highest Shannon-Wiener index (H) and species richness (S) among the seven groups, with extremely significant differences compared with the normal group (P <0.01), significant differences compared with the conventional decoction pieces group and the conventional powder group (P <0.05) and a high intra-group similarity. In conclusion, the long-term intake of 1/8 dose Rhodiolae Crenulatae Radix et Rhizoma cell wall-broken decoction pieces showed a certain effect in regulating intestinal tract by promoting the growth of Lactobacillus and Bifidobacterium. Furthermore, the intestinal flora community will become more stable.
Animals ; Bifidobacterium ; drug effects ; genetics ; growth & development ; Cell Wall ; Denaturing Gradient Gel Electrophoresis ; Intestines ; microbiology ; Lactobacillus ; drug effects ; genetics ; growth & development ; Mice ; Mice, Inbred C57BL ; Polymerase Chain Reaction ; Rhizome ; Rhodiola

AIM:To observe the role of calcium-sensing receptor (CaSR) in the regulation of pulmonary artery tension.METHODS:The intracellular calcium concentration ([Ca2+]i) was detected by laser-scanning confocal micros-copy, and the pulmonary artery tension was determined by the pulmonary arterial ring technique .RESULTS: Increased levels of [Ca2+]o or Gd3+(an agonist of CaSR) induced the increase in [Ca2+]i and pulmonary artery constriction in a concentration-dependent manner.Additionally, the effects of Ca2+and Gd3+were inhibited by U73122 and D609 (specific inhibitor of PLC), and 2-APB and heparin (specific antagonist of IP3 receptor).However, U73343 (U73122 inactive ana-logue) did not take effect.CONCLUSION: CaSR may be involved in the regulation of pulmonary artery tension by in-creasing [Ca2+]i through G-protein-PLC-IP3 pathway.

Case-Control Studies ; Diabetes Mellitus, Type 2 ; epidemiology ; Glucose Tolerance Test ; Humans ; Risk Factors

OBJECTIVE:To compare in vivo and in vitro permeation behaviors of the ethosome gels of testosterone,testoster-one propionate and testosterone undecanoate. METHODS:The ethosome gels of testosterone,testosterone propionate and testoster-one undecanoate were prepared. With cumulative permeating amount and permeation rate as the indexes,Franz diffusion cell and HPLC were employed to compare in vitro permeation behaviors of 3 kinds of ethosome gels in mouse skin. With testosterone patch as the positive control drug, electrochemistry method was adopted to detect the concentration of testosterone in plasma 0,3,6, 9,12,24,36 and 48 h after applying such 3 kinds of ethosome gels on the back of rats,and then pharmacokinetic parameters were calculated with DAS 2.0 software. RESULTS:24 h cumulative permeating amounts of the ethosome gels of testosterone,tes-tosterone propionate and testosterone undecanoate were(234.31±13.8),(175.63±41.1)and(72.60±15.3)μg/cm2,and the per-meation rates were(10.25±1.9),(7.64±1.4)and(2.96±0.8)μg/(cm2·h),respectively. The pharmacokinetic parameters of the above-mentioned three kinds of ethosome gels and the positive control drug were respectively as follows as cmax of(20.19±2.57), (17.50±2.91),(0.23±0.04),(14.97±2.12)ng/ml,t1/2Ka of(2.80±0.45),(3.36±0.59),(4.02±0.62),(4.20±0.71)h,AUC0-48 h of(13.85±1.96),(13.93±2.13),(0.35±0.07),(11.76±2.31)ng·h/ml. CONCLUSIONS:in vivo and in vitro permeation behav-iors of the ethosome gels of testosterone and testosterone propionate are fairly good.

Interactions between noroviruses (NoVs) and the receptors of histo-blood group antigens (HB-GAs) affect the infectivity and host susceptibility of NoVs. We elucidated the binding profile of a GII. 12 NoV to HBGAs. First, we synthesized the P domain sequence of the GII. 12 NoV strain Pune (GenBank accession number EU921353). Protein of the P domain was expressed in a prokaryotic system. Formation of the P particle was monitored by gel-filtration chromatography. Antiserum was prepared by immunization of mice with GII. 12 P particles. The binding profile of the GII. 12 NoV Pune strain was determined by binding of the P particle with a panel of saliva samples with various known HBGAs phenotypes. The GII. 12 NoV was bound strongly to saliva samples of subjects with B and AB types and weakly to A, O secretor, and non-secretor saliva samples, suggesting higher affinity with B antigen by GII. 12 NoV. These results were consistent with those determined by a previous crystallography study of GII. 12 NoV. These data suggested that individuals with B and AB blood types may be more susceptible to infection by GII. 12 NoV compared with those with other blood types. Our findings may provide a basis for the prevention and control of an epidemic of GII. 12 NoV.
Animals ; Blood Group Antigens ; metabolism ; Caliciviridae Infections ; metabolism ; virology ; Female ; Gastroenteritis ; metabolism ; virology ; Genotype ; Humans ; Mice ; Mice, Inbred BALB C ; Norovirus ; genetics ; metabolism ; Protein Binding ; Receptors, Virus ; metabolism ; Viral Proteins ; genetics ; metabolism