Application of micro-pen electrospray ionization tandem mass spectrometry in rapid detection of metabolic stability of testosterone and dextromethorphan / 药学学报

Probe electrospray ionization (PESI) is one of the typical types of ambient ionization technology, but its application in quantitative analysis is limited due to its poor sampling stability. Previously, we developed a new micro-pen electrospray ionization tandem mass spectrometry (μPen-ESI-MS/MS) method based on PESI. In this study, a μPen-ESI-MS/MS method to measure testosterone and dextromethorphan in liver microsome samples was developed and validated to further applicate in evaluating drug metabolism stability and CYP450 enzyme activity. A μPen-ESI-MS/MS method for detecting the CYP3A4 substrate testosterone and CYP2D6 substrate dextromethorphan in the liver microsome incubation system were developed, and the linearity, precision and accuracy of the method was validated. The validated method was further used to detect the metabolic stability of testosterone in the liver microsome incubation system. The results showed that the μPen-ESI-MS/MS had high efficiency with 0.3 min spraying time of each sample. The standard curve of the testosterone and dextromethorphan has good linearity (R2 > 0.99), the intra- and inter-batch accuracy of testosterone and dextromethorphan was 95.9%-109.3% and 90.5%-107.3%, respectively; the intra- and inter-batch precision was acceptable with RSD values of 2.4%-13.5% and 3.4%-12.1%. The half-lives of testosterone and dextromethorphan in the liver microsome incubation system were 12 min and 14 min, respectively. This study provided a rapid and sensitive μPen-ESI-MS/MS method for the assay of testosterone and dextromethorphan in liver microsome samples, and provided a new strategy for the evaluation of drug metabolism stability and CYP3A4/CYP2D6 activity.

Design, synthesis and antiplatelet activity evaluation of novel quinoxaline antagonists of protease activated receptor 4 (PAR4) / 药学学报

Twenty-five compounds of novel quinoxaline-based scaffold with antiplatelet activity were designed and synthesized on the basis of previous quinoxaline analogues, and the structures were confirmed by 1H NMR, 13C NMR, and MS. The antiplatelet activity was evaluated, structure-activity relationship (SAR) study was summarized and the selectivity of PAR4 was confirmed by calcium mobilization assays. It was indicated that compound 14a, 14g, 13i, 13p showed moderate activity against PAR4, especially, the activity of compound 14g (IC50 = 0.26 μmol·L-1) was 6.7 times than the lead compound A (IC50 = 1.73 μmol·L-1). Therefore, 2,3-dihydro-[1,4]dioxino[2,3-g]quinoxaline and [1,3]dioxolo[4,5-g]quinoxaline derivatives are promising compounds for the discovery of novel antiplatelet agents. It is worthy of further research to develop highly effective and selective PAR4 antagonists.

Role and mechanisms of MLKL-NLRP3-mediated necroinflammation in mice with sepsis-induced acute lung injury / 中华危重病急救医学

Objective:To investigate the roles and underlying mechanisms of mixed lineage kinase domain like (MLKL)-mediated inflammatory response induced by NOD-like receptor protein 3 (NLRP3) inflammatory corpuscles in the acute lung injury (ALI) after sepsis.Methods:Eighteen BALB/c mice were randomly divided into sham operation group (Sham group), cecal ligation and perforation (CLP)-induced sepsis model group (CLP group) and specific inhibitor Necrostatin-1 intervention group [CLP+Nec-1 group, Necrostatin-1 solution (20 mg/kg) was injected intravenously 10 minutes before modeling], with 6 mice in each group. The mice were sacrificed by neck amputation at the 2nd day after operation, and the serum and lung tissue samples were collected. The morphological changes of lung tissue were observed by hematoxylin-eosin (HE) staining. The water content of lung tissue was detected by dry-wet weight method. The pulmonary vascular permeability was measured by Evans blue (EB) staining. The protein expressions of MLKL and NLRP3 in the lung tissue were detected by Western blotting, and the level of serum interleukin-1β (IL-1β) was detected by enzyme linked immunosorbent assay (ELISA).Results:HE staining showed that the lung morphological structure in Sham group was normal. In CLP group, congestion and edema in the alveolar cavity and interstitium, infiltration of neutrophils and thickening of alveolar wall were observed. The histopathological changes of lung tissue in CLP+Nec-1 group were better than those in CLP group. Compared with Sham group, the water content of lung tissue [(88.00±0.00)% vs. (78.00±0.01)%], pulmonary vascular permeability [EB content (mg/L): 11.82±1.15 vs. 4.00±0.71], the protein expressions of phosphorylated MLKL (p-MLKL) and NLRP3 in lung tissue (p-MLKL/GAPDH: 0.34±0.04 vs. 0.12±0.01, NLRP3/GAPDH: 0.47±0.07 vs. 0.16±0.04), and the level of serum IL-1β (ng/L: 183.56±9.61 vs. 44.14±6.95) in CLP group were all significantly increased (all P < 0.01). Compared with CLP group, the water content of lung tissue [(81.00±0.01)% vs. (88.00±0.00)%], pulmonary vascular permeability [EB content (mg/L): 7.90±0.00 vs. 11.82±1.15], protein expressions of p-MLKL and NLRP3 in lung tissue (p-MLKL/GAPDH: 0.13±0.03 vs. 0.34±0.04, NLRP3/GAPDH: 0.18±0.04 vs. 0.47±0.07), and the level of serum IL-1β (ng/L: 113.81±6.62 vs. 183.56±9.61) were all significantly decreased (all P < 0.01). Conclusion:MLKL-NLRP3-mediated necroinflammation was significantly up-regulatedin the lung tissue of septic mice, which could be attenuated by specific inhibitor Necrostatin-1.

blaIMP-45 and armA co-carrying multidrug resistance Pseudomonas isolates and characterization of their genetic environment / 中华检验医学杂志

Objective The primary goal of this work is to discuss the molecular mechanism of multi-drug resistant Pseudomonas spp. resistance to carbapenam and aminoglycoside antibiotics. Methods From June 2012 to March 2013, six strains of P. aeruginosa and P. putida producing carbapenemasefrom 4 different district were collected. Species identification was performed using VITEK-2 compact system and by sequencing of 16S rDNA amplicons. Minimum inhibitory concentrations were determined by E-test method. Production of carbapenemase were detected by Carba NP method. Carbapenemase genes and aminoglycoside 16s rRNAmethylase genes were screened by PCR, and their subtypes combined with their immediate genetic context were worked out by assemble the sequence of overlapped PCR amplicons. SpeI-PFGE (Pulse field gel electrophoresis after SpeI enzyme digestion) were conducted to evaluate their clonal relatedness. S1-PFGE (Pulse field gel electrophoresis after S1 enzyme digestion) were conducted to conform the relatedness of plasmids they carried. Results Three multidrug resistant P. aeruginosa and three P. putida, were all positive for Carba NP test and conformed producing class B carbapenemase. PCR screening followed by sequencing confirmed carriage of blaIMP-45 and armA, which confer resistance to β-lactams (except aztreonam) and aminoglycosides. These two genes co-located in a Tn1548-associatedregion. SpeI-PFGE disclosed that these isolates were not clonal closely related to each other, except two P. aeruginosa isolates were clonal related. S1-PFGE results showed that these isolates all carried plasmids of large size (300-600 kb). Conclusions This study showed that Pseudomonas spp. isolates co-carried blaIMP-45 and armA were disseminated in clinical settings. Spread of these genes may attribute to horizontal gene transfer of related entities.

Clinical results of HCR compared with OPCABG on two-vessel coronary artery disease with proximal left anterior descending stenosis: a propensity-score-matched follow-up study / 上海交通大学学报（医学版）

Objective: To explore the difference between hybrid coronary revascularization (HCR) and off-pump coronary artery bypass grafting (OPCABG) on two-vessel coronary artery disease with proximal left anterior descending stenosis with propensity score matching. Methods: The patients with two-vessel coronary artery disease with proximal left anterior descending stenosis who underwent isolated HCR or OPCABG were selected in Ruijin Hospital from January 2009 to December 2016. The propensity score methodology was used to obtain risk-adjusted outcome. Kaplan-Meier analysis was applied to estimation of major adverse cardiac and cerebrovascular events (MACCE)-free survival rate and target vessel revascularization (TVR)-free survival rate. Results: The average follow-up time was 59 months (13-104 months). The length of hospital stay of HCR group was significantly shorter than that of OPCABG group [(15.3±4.5) d vs (17.6±5.4) d, P=0.027]. There was no statistical difference in other short-term clinical endpoints in hospital. In midterm, there was no statistical difference in the rate of MACCE (11.4% vs 13.3%, P=0.968), death (2.3% vs 4.4%, P=0.984), myocardial infarction (2.3% vs 2.2%, P=0.485), stroke (4.5% vs 6.7%, P=0.979) and TVR (4.5% vs 2.2%, P=0.984) between two groups. And there was no statistical difference in MACCE-free survival rate (P=0.906) and TVR-free survival rate (P=0.541) between two groups. Conclusion: HCR provides favorable midterm outcomes for selected patients with two-vessel coronary artery disease with proximal left anterior descending stenosis. It might provide a promising alternative to OPCABG.

Clinical results of HCR compared with OPCABG on two-vessel coronary artery disease with proximal left anterior descending stenosis: a propensity-score-matched follow-up study / 上海交通大学学报（医学版）

Objective·To explore the difference between hybrid coronary revascularization (HCR) and off-pump coronary artery bypass grafting (OPCABG) on two-vessel coronary artery disease with proximal left anterior descending stenosis with propensity score matching.Methods·The patients with two-vessel coronary artery disease with proximal left anterior descending stenosis who underwent isolated HCR or OPCABG were selected in Ruijin Hospital from January 2009 to December 2016.The propensity score methodology was used to obtain risk-adjusted outcome.Kaplan-Meier analysis was applied to estimation of major adverse cardiac and cerebrovascular events (MACCE)-free survival rate and target vessel revascularization (TVR)-free survival rate.Results·The average follow-up time was 59 months (13-104 months).The length of hospital stay of HCR group was significantly shorter than that of OPCABG group [(15.3±4.5) d vs (17.6±5.4) d,P=0.027].There was no statistical difference in other short-term clinical endpoints in hospital.In midterm,there was no statistical difference in the rate of MACCE (11.4％ vs 13.3％,P=0.968),death (2.3％ vs 4.4％,P=0.984),myocardial infarction (2.3％ vs 2.2％,P=0.485),stroke (4.5％ vs 6.7％,P=0.979) and TVR (4.5％ vs 2.2％,P=0.984) between two groups.And there was no statistical difference in MACCE-free survival rate (P=0.906) and TVR-free survival rate (P=0.541) between two groups.Conclusion·HCR provides favorable midterm outcomes for selected patients with two-vessel coronary artery disease with proximal left anterior descending stenosis.It might provide a promising alternative to OPCABG.

Analysis on level of serum vitamin D in patients with lower respiratory tract infection / 国际检验医学杂志

Objective To investigate the change of serum vitamin D level in the patients with lower respira-tory tract infection and its correlation with lower respiratory tract infection so as to provide reference for clini-cal treatment.Methods 156 cases of lower respiratory tract infection and 60 persons undergoing healthy phys-ical examination in this hospital were collected as the infection group and healthy control group.The sputum specimens from the infection group conducted the bacterial culture and identification.Then the serum vitamin D levels were analyzed in the two groups.Results The serum vitamin D levels in the infection group and healthy control group were 25.76 ng/mL and 49.81 ng/mL,and the difference was statistically significant (P<0.01).In the infection group,serum vitamin D levels in the patients with klebsiella pneumoniae,Acine-tobacter baumannii,Pseudomonas aeruginosa,staphylococcus aureus,Escherichia coli and fungal infection w ere(25.79 ± 7.17),(24.11 ± 10.27),(27.76 ± 9.27),(24.79 ± 6.95),(22.93 ± 3.71)and(30.59 ± 21.31) ng/mL respectively,the difference had statistical significance compared with the control group(P<0.05). Conclusion The level of serum vitamin D in the patients with lower respiratory tract infection is lower than that in healthy population.Its level is associated with lower respiratory tract infection,but the specific mech-anism remains to be further studied.

Effects of Yiqi Huoxue Xiaozheng Formula on Apoptosis of Rats with Benign Prostatic Hyperplasia / 中国中医药信息杂志

Objective To investigate the effects of Yiqi Huoxue Xiaozheng Formula on cell apoptosis in rats with benign prostatic hyperplasia (BPH); To preliminarily explore its mechanism of action. Methods Totally sixty 8-week-old male SD rats were randomly devided into normal group, positive control group, Yiqi Huoxue XiaozhengFormula low-, medium-, and high-dose groups, with 10 rats in each group. Except for the rats in normal group, rats in other groups were treated with castrate and testosterone propionate injection to replicate BPH model. The normal group and the model group were given normal saline for gavage; Yiqi Huoxue Xiaozheng Formula low-, middle-, and high-dose groups were given Yiqi Huoxue Xiaozheng Formula 10, 20, 40 mg/100 g for gavage, respectively; rats in positive control group were given Longkai Granule suspension 11 mg/100 g for gavage, once a day, for 30 d. Twenty-four hours after the last administration, the rats were sacrificed by cervical dislocation. The prostate tissue was taken. The protein expressions of Bcl-2 and Bax in the prostate tissue were detected by immunohistochemistry. Results Compared with the normol group, the expression of Bax in the prostate tissue of the model group decreased significantly, while the expression of Bcl-2 increased significantly; Compared with the model group, the expression of Bax in the prostate tissue of rats in administration groups increased significantly, while the expression of Bcl-2 was significantly reduced, and Yiqi Huoxue Xiaozheng Formula high-dose group was superior to other groups. Conclusion Yiqi Huoxue Xiaozheng Formula can improve benign prostatic hyperplasia by promoting the apoptosis of rat prostate tissue, and its mechanism is related to the increase of the expression of Bax protein and the decrease of Bcl-2 protein expression in prostate tissue.

Clinical distribution and drug resistance of 213 strains of ESBLs-producing Klebsiella pneumoniae in general hospitals / 国际检验医学杂志

Objective To investigate the specimen source and gene phenotype of ESBLs in ESBLs-producing Klebsiella pneumonia of people′s hospital of Sanya city,so as to provide basis for clinical use of drugs and nosocomial infection.Methods Klebsiella pneumoniae was isolated from specimens during January 2013 to December 2014,bacteria identification and susceptibility tests were detected by Phoenix-100 system biochemical,supplementary susceptibility test was confined by K-B method according to 2014 CLSI standards.WHONET 5.6was used in the statistical analysis of all data.Results Totally 213 strains Klebsiella pneumoniae were isolated.The detection rates were 78.4％ of the respiratory secretions,8.92％ and 5.2％ respectively of the secretion and the midstream urine.The strains had a certain resistance to commonly used antimicrobial.The highest resistance rate was 98.1％ to cefotaxime,and the lowest resistance rate was 2.86％ to imipenem.There were 195 in 213 ESBLs producing Klebsiella pneumoniae strain were detect one or more drug resistance gene.The detecting rates of 6 p-lactamase gene of CMY,CTX,TEM,SHV,DHA1 and KPC were 6.10％,76.53％,59.62％,76.06％,12.21％ and 2.82％.Conclusion Klebsiella pneumoniae is mainly isolated from respiratory secretions in the hospital,has a certain resistance to commonly used antimicrobial.We should learn more about the distribution of resistance genes of ESBLs strains,improve the efficiency of the treatment of the infection and to control nosocomial infection and the incidence of multi-drug resistance.

Homology analysis and historical tracing for inter-continental Burkholderia pseudomallei strains of sequence type 562 / 中华流行病学杂志

Objective To understand the homology of sequence type 562 (ST562) strains of Burkholderia pseudomallei which circulated in two separate continents (Asia and Australia) at different times.Methods Spe Ⅰ restriction fragments and 4-locus multiple locus variable number tandem repeat analysis (MLVA-4) profiles were extracted from MSHR5858 (ST562 Australia strain) and 350105 (ST562 historical strain of Hainan) genomes respectively by in silico analysis and then compared with the PFGE and MLVA-4 results of five ST562 clinical isolates from Hainan to test their homology.Synteny and homology between MSHR5858 and 350105 genomes were evaluated with bioinformatics methods.Results Five ST562 clinical strains from Hainan shared same PFGE pattern (similarity ＞97％) and this pattern coincided to the map of Spe Ⅰ restriction fragments of Australian strain MSHR5858.The amounts of genomic restriction fragments (Spe Ⅰ) for MSHR5858 and 350105 were 31 and 34 respectively,with 31 of them matched by each other.Five ST562 clinical strains of Hainan were distinct by MLVA-4 profiles,among which HPPH43 (MLVA-4 profile:10,8,10,8) was close to Australia strain MSHR5858 (10,8,8,6),containing identical repeat numbers at VNTR loci 2341k and 1788k;while HK003 (11,8,15,7) and HK061 (11,8,17,7) similar to Hainan historical strain 350105 (11,8,11,8),with same repeat numbers at loci 2341k and 1788k also.High-degree synteny and consistency on genomic contents were observed between 350105 and MSHR5858,indicating a similar origin for the 2 strains.Conclusion All inter-continental and historical ST562 strains ofB.pseudomallei had similar genomic characteristics,supporting the assumption that they had a common origin.Also,it is possible that Hainan historical strain 350105 is the ancestor of all circulating ST562 strains.

Homology analysis and historical tracing for inter-continental Burkholderia pseudomallei strains of sequence type 562 / 中华流行病学杂志

Objective To understand the homology of sequence type 562 (ST562) strains of Burkholderia pseudomallei which circulated in two separate continents (Asia and Australia) at different times.Methods Spe Ⅰ restriction fragments and 4-locus multiple locus variable number tandem repeat analysis (MLVA-4) profiles were extracted from MSHR5858 (ST562 Australia strain) and 350105 (ST562 historical strain of Hainan) genomes respectively by in silico analysis and then compared with the PFGE and MLVA-4 results of five ST562 clinical isolates from Hainan to test their homology.Synteny and homology between MSHR5858 and 350105 genomes were evaluated with bioinformatics methods.Results Five ST562 clinical strains from Hainan shared same PFGE pattern (similarity ＞97％) and this pattern coincided to the map of Spe Ⅰ restriction fragments of Australian strain MSHR5858.The amounts of genomic restriction fragments (Spe Ⅰ) for MSHR5858 and 350105 were 31 and 34 respectively,with 31 of them matched by each other.Five ST562 clinical strains of Hainan were distinct by MLVA-4 profiles,among which HPPH43 (MLVA-4 profile:10,8,10,8) was close to Australia strain MSHR5858 (10,8,8,6),containing identical repeat numbers at VNTR loci 2341k and 1788k;while HK003 (11,8,15,7) and HK061 (11,8,17,7) similar to Hainan historical strain 350105 (11,8,11,8),with same repeat numbers at loci 2341k and 1788k also.High-degree synteny and consistency on genomic contents were observed between 350105 and MSHR5858,indicating a similar origin for the 2 strains.Conclusion All inter-continental and historical ST562 strains ofB.pseudomallei had similar genomic characteristics,supporting the assumption that they had a common origin.Also,it is possible that Hainan historical strain 350105 is the ancestor of all circulating ST562 strains.

Effect of integrated Chinese and Western medicine therapy on severe hand, foot and mouth disease: A prospective, randomized, controlled trial / 中国结合医学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of Chinese medicine (CM) plus Western medicine (WM) in the treatment of pediatric patients with severe hand, foot and mouth disease (HFMD) by conducting a prospective, controlled, and randomized trial.</p><p><b>METHODS</b>A total of 451 pediatric patients with severe HFMD were randomly assigned to receive WM therapy alone (224 cases, WM therapy group) or CM [Reduning Injection ( ) or Xiyanping Injection ()] plus WM therapy (227 cases, CM plus WM therapy group) for 7-10 days, according to a web-based randomization system. The primary outcome was fever clearance time, which was presented as temperature decreased half-life time. The secondary outcomes included the rate of rash/herpes disappearance within 120 h, as well as the rate for cough, runny nose, lethargy and weakness, agitation or irritability, and vomiting clearance within 120 h. The drug-related adverse events were also recorded.</p><p><b>RESULTS</b>The temperature decreased half-life time was 40.4 h in the WM therapy group, significantly longer than 27.2 h in the CM plus WM therapy group (P<0.01). Moreover, the rate for rash/herpes disappearance within 120 h was 43.6% (99/227) in the CM plus WM therapy group, significantly higher than 29.5% (66/224) in the WM therapy group (P<0.01). In addition, the rate for cough, lethargy and weakness, agitation or irritability disappearance within 120 h was 32.6% (74/227) in the CM plus WM therapy group, significantly higher than 19.2% (43/224) in the WM therapy group (P<0.01). No drug-related adverse events were observed during the course of the study.</p><p><b>CONCLUSION</b>The combined CM and WM therapy achieved a better therapeutic efficacy in treating severe HFMD than the WM therapy alone. Reduning or Xiyanping Injections may become an important complementary therapy to WM for relieving the symptoms of severe HFMD. (Registration No. NCT01145664).</p>

Microdecompression for intraforaminal lumbar disc herniations / 中国骨伤

<p><b>OBJECTIVE</b>To summarize clinical results of the microdecompression for the treatment of intraforaminal lumbar disc herniations.</p><p><b>METHODS</b>From September 2005 to May 2013,16 patients( 12 males, 4 females)with intraforaminal lumbar disc herniations underwent microdecompression, ranging in age from 32 to 56 years old with a mean of 38.6 years old. The lumbar disc herniations were located at L(3,4). in one patient, L(4,5) in 10 cases and L5S1 in 5 cases.</p><p><b>RESULTS</b>All the patients were followed up, and the duration ranged from 20 to 48 months, with a mean period of 36 months. According to Macnab evaluation, 12 cases got an excellent result, 4 good. No apparent complications related to the technique occurred. Satisfactory clinical results were obtained in this series.</p><p><b>CONCLUSION</b>Microdecompression may be particularly useful in the treatment of intraforaminal lumbar disc herniations. The microdecompression procedures are more likely to be well tolerated by older patients.</p>

Analysis and synthesis of the related substances of palbociclib / 中国药科大学学报

@#To strengthen the quality control of palbociclib, three related substances were separated from the bulk drug. These substances were identified as 8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido ［2, 3-d］ pyrimidin-7(8H)-one(A), 8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridine-2-yl)amino)-6-vinylpyrido ［2, 3-d］ pyrimidin-7(8H)-one(B), tert-butyl4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7, 8-dihydropyrido ［2, 3-d］ pyrimidin-2-yl)amino)pyridin-3-yl)piperazi-ne-1-carboxylate(C). Based on the structures of the impurities, the possible routes to them were discussed, and their structures were elucidated by 1H NMR and MS.

Association of single nucleotide polymorphisms of CSPG2 and HSPG2 genes with intracranial aneurysm in ethnic Han Chinese population / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association between CSPG2 and HSPG2 gene polymorphisms and intracranial aneurysm (IA) in ethnic Han Chinese population.</p><p><b>METHODS</b>A case-control study was carried out. A total of 537 IA patients and 1071 normal controls with matched age and gender were recruited. Peripheral blood samples were obtained from all subjects. Following extraction, target DNA was amplified with PCR and genotyped with a SNaPshot method. The association between 2 tag SNPs (rs251124 and rs3767137) of CSPG2 and HSPG2 genes and IA was assessed.</p><p><b>RESULTS</b>The genotype frequencies of rs251124 and rs3767137 were both in Hardy-Weinberg equilibrium. No significant difference has been found in the frequencies of rs251124 of CSPG2 between the two groups. Similarly, the frequency of rs3767137 (HSPG2) did not differ between the IA and control groups (P=0.22), albeit with an OR value of greater than 1 (OR=1.12, 95%CI=0.92-1.37). There were no significant difference in genotypic frequencies of the two SNPs between the two groups (P=0.46, 0.53).</p><p><b>CONCLUSION</b>No association has been found between polymorphisms of rs251124 and rs3767137 loci of CSPG2 and HSPG2 genes and IA in the selected population.</p>

Synthesis and biological evaluation of novel diphenyl methane sulfinyl and diphenylthio-acetamide derivatives / 药学学报

According to the structure-activity relationships (SARs) of modafinil, a therapeutic drug of hypnolepsy, we designed and synthesized two series of compounds 2-[(diphenylmethane)sulfinyl] acetamides and 2-[(diphenylmethyl)thio] acetamides, and measured their biological activities. The target compounds (6a-6o) were synthesized beginning with diphenyl carbinol by substitution, oxidation, acylation and so on. Their structures were confirmed by ESI-MS, 1H NMR and elemental analysis. The central stimulatory effects of the target compounds were determined by the independent activity assay on mice. Compounds 6c, 6f and 6n have considerable activities, while the central stimulative effect of 6h is slightly better than the positive control modafinil.

Synthesis and biological evaluation of novel diphenyl methane sulfinyl and diphenylthio-acetamide derivatives / 药学学报

According to the structure-activity relationships (SARs) of modafinil, a therapeutic drug of hypnolepsy, we designed and synthesized two series of compounds 2-[(diphenylmethane)sulfinyl] acetamides and 2-[(diphenylmethyl)thio] acetamides, and measured their biological activities. The target compounds (6a-6o) were synthesized beginning with diphenyl carbinol by substitution, oxidation, acylation and so on. Their structures were confirmed by ESI-MS, 1H NMR and elemental analysis. The central stimulatory effects of the target compounds were determined by the independent activity assay on mice. Compounds 6c, 6f and 6n have considerable activities, while the central stimulative effect of 6h is slightly better than the positive control modafinil.

Experimental study on co-culture of salivary adenoid cystic carcinoma cells and ganglia / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To construct the co-culture models of salivarya denoid cystic carcinoma (SACC) cells and dorsal root ganglia (DRG) of chickens and investigate the promotive effects of SACC on neural tissue.</p><p><b>METHODS</b>Glass-base culture dish was adopted to construct co-culture model of SACC-83 cells and DRG. SACC-83 cells were seeded in the medium pore with DRG around them. Outgrowth of neuronal processes was observed. Then DRG was cultured in the conditioned medium of SACC-83, with the groups of conditioned medium of MC3T3-E1 and HGF, the group of cell lysis buffer, the groups of serum-free medium and serum-plus medium as the controls. Outgrowth of neuronal processes was also recorded and compared with control groups.</p><p><b>RESULTS</b>In the co-culture model of tumor and neuronal tissue, SACC-83 cells produced a suitable microenvironment in which neuronal processes remarkably grow. Neuronal processes of most DRG displayed growth tendency toward SACC. The group of conditioned medium from SACC-83 manifested obvious promotive effects on DRG.</p><p><b>CONCLUSIONS</b>Co-culture model of tumor and neuronal tissue was successfully constructed, with which the promotive effects of tumor on outgrowth of neuronal processes could be observed. So hypothesized that SACC could secrete some neurotrophic factors to guide peripheral nerves gemmating and to trigger the cascade of the neural invasion in succession.</p>