Objective To optimize the synthesis process of iloperidone 1 for industrial production.Methods Piperi-dine-4-carboxylic acid, acetic acid and acetic anhydride were used as starting materials to generate 2 via amidation, Friedel-Crafts acylation, hydration, oximation, intramolecular cyclization and salification.Compound 2 was treated with 4-(3-chloropropoxy)-3-methoxyphenylethanone through condensation to afford iloperidone.The target compound 1 was prepared with an overall yield of 34.9%.Results and Conclusion Such factors as the ratio of the raw materials, the catalyst, reactive time were investigated and optimized to make the reaction conditions mild and easy to control with less side effects.The structure has been confirmed by IR, 1 H-NMR and MS.

BACKGROUND: Biomechanical mechanisms are complex, and previous studiers focus on the stress conduction in the carpus. However, the stress distribution and characteristics of trabecula in the carpus are rarely reported.OBJECTIVE: To investigate the stress distribution and deformation characteristics of the normal lunate through a two-dimensional sagittal finite element model.METHODS: A normal cadaveric lunate sample was scanned with Micro-CT and the central sagittal image was chosen for further finite element analysis (FEA). The chosen image was processed and imported into the finite element analysis software (Ansys 14.0). A two-dimensional sagittal finite element model of the lunate bone was established. Axial pressure was applied to the model with the wrist held in different positions, and nine regions of interests (ROIs) were identified, for which stress and displacement nephograms were created. These included the first principal stress (S1, the maximum stress in a principal plane), the third principal stress (S3, the minimal stress in a principal plane), shear stress (SXY, the component of stress coplanar with a material cross section), von Mises stress (SEQV, yielding begins when the elastic energy of distortion reaches a critical value)and displacement of each ROI (UY, displacement on the vertical plane of the lunate) which were calculated and compared.RESULTS AND CONCLUSION: (1) The stresses on ROIs located in the proximal and volar cortices of the lunate bone were much higher than those in the distal and dorsal cortices. At the proximal lunate, S1 was less than S3; however at the distal lunate, S1 was greater than S3. The ROIs of the distal and proximal ends of the lunate bone received much higher stress than the ROIs of the middle part. As for axial trabecular displacement,both distal and proximal ROIs were compressed by axial pressure. However, the dorsal and the volar parts of the proximal lunate moved in different directions at different wrist postures. Besides, the stress values and magnitudes of displacement were elevated in wrist flexion and extension compared to neutral position.Furthermore, the stress concentration zones (the proximal volar ROI, the proximal dorsal ROI, the distal volar ROI, and the distal dorsal ROI) had different directions of shear stress and displacement in different wrist postures. (2) These results suggest that when stress is loaded on a normal lunate model, four stress concentration zones, the proximal volar ROI, the proximal dorsal ROI, the distal volar ROI, and the distal dorsal ROI are found. The wrist postures can significantly affect the value and distribution of axial stress on the sagittal lunate.

Objectve To optimize the synthesis process of phacolysin 1 for industrial production.Methods Phacolysin as the target product was synthesized with a total yield of 40.7% by condensation reaction of O-phenylenediamine and sulfonation reaction.The yield reported in literature was 24.8%.Results Such factors as the ratio of the raw materials,the catalyst,and the reaction time were inveatigated and optimized to make the reaction conditions mild and easy to control with less side effect.Conclusion The structure is confirmed by 1HNMR and MS,and the optimized process is more suitable for industrial production.

Castleman Disease ; Humans ; Male ; Middle Aged ; Neck ; Young Adult

Objective To optimize the synthesis process of istradefylline 1 for industrial production.Methods Istrade-fylline was synthesized from dimethyl carbonate and ethylamine through a series reactions including condensation,cycliza-tion,nitrosation,and reduction to produce 1,3-diethyl-5,6-diaminouracil(6),which was subjected to amidation with (E)-3,4-dimethoxycinnamic acid (8),followed by cyclization and methylation reaction.Compound 8 was prepared from veratr-aldehyde and propanedioic acid by Knoevenagel condensation.The structures of intermediate and target compounds were confirmed by MS and 1 H-NMR.Results and Conclusion The quality control points of each key process were optimized so that the total yield was 26.2% and the purity of the product was 99.76%.This improved synthesis method has some advan-tages,such as mild reaction conditions,simple operation,and applicability to industrial production.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Non-Small-Cell Lung ; genetics ; Female ; Genes, erbB-1 ; genetics ; Humans ; Lung Neoplasms ; genetics ; Male ; Middle Aged ; Mutation ; Nucleic Acid Amplification Techniques ; methods ; Receptor, Epidermal Growth Factor ; genetics

OBJECTIVETo discuss the feasibility of vascular bundle implantation combined with allogeneic bone marrow stromal cells (BMSCs) transplantation in treating rabbit femoral head osteonecrosis and bone defect, in order to explore a new method for the treatment of femoral head necrosis.

METHODSThirty-six New Zealand rabbits were randomly divided into three groups,with 12 rabbits in each group. Bilateral femoral heads of the rabbits were studied in the experiment. The models were made by liquid nitrogen frozen, and the femoral heads were drilled to cause bone defect. Group A was the control group,group B was stem cells transplantaion group of allograft marrow stromal,and group C was stem cells transplantation group of allograft marrow stromal combined with vascular bundle implantation. Three rabbits of each group were sacrificed respectively at 2, 4, 8, 12 weeks after operation. All specimens of the femoral heads were sliced for HE staining. Furthermore ,vascular density and the percentage of new bone trabecula of femoral head coronary section in defect area were measured and analyzed statistically.

RESULTSIn group C,new bone trabecula and original micrangium formed at the 2nd week after operation; new bone trabecula was lamellar and interlaced with abundant micrangium at the 8th week;at the 12th week,the broadened,coarsened bone trabecula lined up regularly,and the mature bone trabecula and new marrow were visible. At the 2nd week after operation,there was no statistical significance in the percentage of new bone trabecula of femoral head coronary section in defect area between group B and C. While at 4, 8, 12 week after operation, vascular density and the percentage of new bone trabecula of femoral head coronary section in defect area of group C was higher than that of group B.

CONCLUSIONAllogeneic bone marrow stromal cells cultured in vivo can form new bone trabecula, and can be applied to allotransplant. Vascular bundle implanted into the bone defect area of femoral head necrosis could improve blood supply, and promote the formation of bone trabecula.

Animals ; Blood Vessels ; transplantation ; Combined Modality Therapy ; Female ; Femur Head Necrosis ; pathology ; surgery ; Male ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells ; Rabbits ; Transplantation, Homologous

Activation of the innate immune system requires recognition of pathogen-associated molecular patterns, such as NOD-like receptors. The NOD-like receptor protein 3 (NLRP3) inflammasome is involved in induction of the pro-inflammatory cytokine, IL-1beta, and subsequent inflammatory responses. NLRP3 inflammasome plays important roles in the inflammatory and innate immune responses associated with autoimmune/inflammatory syndrome. However, analysis of the tissue distribution and expression profiles in BALB/c mice is still incomplete. In this study, we investigated the tissue distribution and expression pattern of NLRP3 in BALB/c mice to further elucidate its function in innate immunity in this commonly used laboratory animal model. NLRP3 mRNA expression levels and tissue distribution of the protein were investigated by real-time quantitative PCR and immunohistochemical analyses, respectively. NLRP3 mRNA expression was higher in the kidney and inguinal lymph nodes than in other tissues. Cytoplasmic expression of NLRP3 was detected in the epithelial reticular cells of the spleen and thymus, lymphocytes in the inguinal lymph nodes, cardiac muscle cells, cerebral cortex neurons, alveolar macrophages, renal tubule cells and liver sinusoidal endothelial cells. The results of this study will assist investigators in interpreting site-specific functions and roles of NLRP3 in inflammatory responses.
Animals ; Carrier Proteins/*genetics/metabolism ; *Gene Expression Regulation ; *Immunity, Innate ; Mice ; Mice, Inbred BALB C ; Molecular Sequence Data ; Organ Specificity ; RNA, Messenger/genetics/metabolism ; Real-Time Polymerase Chain Reaction ; Sequence Analysis, DNA

OBJECTIVETo develop a tight tetracycline-controlled HCV-C double transgenic mouse model.

METHODSBy crossbreeding of ApoE-rtTA-tTS transgenic mice with TRE-HCV-C transgenic mice, the double transgenic mice were produced in the F1 generation. The presence of HCV-C and tTS gene in the F1 generation was confirmed by PCR, followed by further identification and quantification of the transgene using Southern blot hybridization. The expression of HCV-C in the liver of the mouse model was detected immunohistochemically.

RESULTS AND CONCLUSIONTwo transgenic mice were obtained, which contained ApoE-rtTA-tTS and TRE-HCV-C genes in the genome. Five founders contained HCV-C gene as confirmed by PCR and Southern blot hybridization. The tight tetracycline-controlled system may facilitate further study of HCV-C gene expression and gene therapy of hepatic cellular carcinoma.

Animals ; Apolipoproteins E ; genetics ; Blotting, Southern ; Breeding ; Crosses, Genetic ; Female ; Gene Expression Regulation, Viral ; drug effects ; Hepacivirus ; genetics ; immunology ; Hepatitis C Antigens ; genetics ; immunology ; Male ; Mice ; Mice, Transgenic ; Polymerase Chain Reaction ; Tetracycline ; pharmacology ; Trans-Activators ; genetics ; Viral Core Proteins ; genetics

In the present study, extracellular recording was used to examine the neuronal activity of the basolateral nucleus (BL) of the amygdala and the effects of systemic administration of the selective 5-HT(1A) receptor antagonist WAY-100635 on the neuronal activity in the normal rats and rats with 6-hydroxydopamine (6-OHDA)-produced lesions in the substantia nigra pars compacta (SNc). The results showed that the firing rates of BL projection neurons and interneurons were (0.39±0.04) Hz and (0.83±0.16) Hz in the normal rats, and (0.32±0.04) Hz and (0.53±0.12) Hz in 6-OHDA-lesioned rats. There was no significant difference in the firing rates of BL projection neurons and interneurons between the normal and 6-OHDA-lesioned rats. In the normal rats, all BL projection neurons fired in burst; 94% of BL interneurons fired in burst and 6% fired irregularly. In 6-OHDA-lesioned rats, 85% of BL projection neurons displayed a burst firing pattern and 15% fired irregularly; 86% of BL interneurons had a burst firing pattern and 14% fired irregularly. The distribution of firing patterns of projection neurons and interneurons in the BL in 6-OHDA-lesioned rats did not differ from that in the normal rats. Systemic administration of WAY-100635 at 0.1 mg/kg body weight did not change the mean firing rates of projection neurons and interneurons in the BL in both normal and 6-OHDA-lesioned rats. However, a higher dose of WAY-100635 at 0.5 mg/kg body weight significantly decreased the mean firing rate of BL projection neurons from (0.43±0.07) to (0.15±0.02) Hz in the normal rats (P<0.01), but significantly increased the activity of BL projection neurons in 6-OHDA-lesioned rats from (0.37±0.08) to (0.69±0.18) Hz (P<0.004). The mean firing rates of BL interneurons in the normal and 6-OHDA-lesioned rats did not change after administration of a higher dose of WAY-100635 at 0.5 mg/kg body weight. These results demonstrate that the activity of BL neurons after substantia nigra dopaminergic lesion in the SNc is regulated by activation of intrinsic and extrinsic inputs, and that 5-HT(1A) receptors significantly contribute to the regulation of the activity of BL projection neurons in both normal and 6-OHDA-lesioned rats. Furthermore, WAY-100635 induced an increase in the mean firing rate of projection neurons in the BL in 6-OHDA-lesioned rats, suggesting that 5-HT(1A) receptor is likely to play a role in generating affective symptoms in Parkinson's disease.
Action Potentials ; Amygdala ; drug effects ; Animals ; Neurons ; drug effects ; Oxidopamine ; adverse effects ; Piperazines ; pharmacology ; Pyridines ; pharmacology ; Rats ; Receptor, Serotonin, 5-HT1A ; Serotonin 5-HT1 Receptor Antagonists ; pharmacology ; Substantia Nigra ; pathology