Combining the structural features of picotamide and linotroban, a series of N,N'-bis-(halogenophenyl)-4-methoxybenzene-1, 3-disulfonamides were designed and synthesized on the basic principles of drug design. The structures of target compounds were confirmed by IR, 1H NMR and HR-MS, and the in vitro antiplatelet aggregation activity was evaluated by Born turbidimetric method with adenosine diphosphate (ADP) as the platelet aggregation inducers. The assay results showed that twelve compounds (4b, 4f, 4l, 5b, 5d-5g, 5j, 5k, 5m and 5n) were found to have superior anti-platelet aggregation activities than the positive drug picotamide. The preliminary structure-activity relationship (SAR) has been explored.
Adenosine Diphosphate ; Drug Design ; Phthalic Acids ; Platelet Aggregation ; Platelet Aggregation Inhibitors ; chemical synthesis ; chemistry ; Structure-Activity Relationship ; Sulfonamides ; chemical synthesis ; chemistry

Traditional Chinese medicine(TCM)is a medical science about the physiological state and disease process of human body.It contains the universality of general thinking methods and the particularity of oriental cultural thinking.Starting from the necessity of the construction of clinical thinking mode of TCM and based on the philosophical features of TCM,this paper re-examines and analyzes the importance of the thinking mode for the nature of disease,and puts forward the six-dimensional differentiation system for TCM clinical practice,which covers disease differentiation,syndrome differentiation,symptom differentiation,pathogenesis differentiation,constitution differentiation and qi differentiation.Guided by the thinking mode of six-dimensional differentiation system,the TCM clinical practice exerts holistic view:disease differentiation is advocated to combine syndrome differentiation;symptom differentiation is mainly for the primary symptoms,which can clarify the transformation of pathogenesis,the progression of the disease,and the evolution of the syndromes;pathogenesis differentiation focuses on the evolution of pathogenesis,and treatment based on syndrome differentiation and modification of drugs based on symptoms are required;constitution differentiation should be made on the basis of the patient's constitution,and detailed identification of the etiology,disease location,disease nature,and progression of the disease should also be conducted;qi differentiation should be made on the basis of the comprehensive consideration of the exuberance and decline of healthy qi and pathogenic qi,thus to ensure the treatment adapting to the individuality,climate,and environment.The establishment of six-dimensional differentiation system aims to expound the internal mechanism of key points for disease differentiation,therapeutics based on syndrome differentiation,drug modification according to symptom differentiation,and differentiation of pathogenesis and illness state,which is helpful to the overall grasp of the disease,pathogenesis,syndrome and treatment in clinical practice,and will provide theoretical basis for the precise treatment of disease.

OBJECTIVETo study the combination of Mandibular distraction and orthognathic techniques for the reconstruction of adult hemifacial microsomia.

METHODSThe three-dimensional CT reconstruction data was used with Mimics for preoperation design. The osteotomy location, distraction vector, distraction distance were decided before operation with a surgical guider. At the first stage, internal distractor was implanted after ostetomy through an extra-oral approach. The distraction begun 5-7 days after operation with a frequency of 1 mm/day. After distraction, the distractor was maintained for 3-6 months. At the second stage, the distractor was removed. Le Fort I osteotomy was performed in order to correct the cross-bite and improve the facial contour. Usually, bone graft was inserted into the gap after Le Fort I osteotomy. The genioplasty was also performed if necessary.

RESULTS9 cases of adult hemifacial microsomia with severe mandibular deviation were treated. The facial asymmetry were improved greatly. 1 patient suffered an wound infection in the maxillary region after Le Fort I osteotomy and healed uneventfully with wound irrigation.

CONCLUSIONSMandibular distraction combined with orthognathic surgery is an effective procedure for adult hemifacial microsomia with complicated mandibular hypoplasia.

Adult ; Aged ; Bone Transplantation ; Facial Asymmetry ; surgery ; Goldenhar Syndrome ; surgery ; Humans ; Mandible ; surgery ; Osteogenesis, Distraction ; methods ; Osteotomy, Le Fort ; methods

Depression is a serious mental illness with a high incidence. At present, we do not fully understand the specific pathological mechanisms of depression, and the efficacy of drug treatments is very limited. Recent studies have shown that epigenetic changes that occur in specific brain regions may be a key mechanism by which environmental factors to interact with individuals to influence the risk of depression. Therefore, drugs that target epigenetic regulation may become a new direction for the development of antidepressants. Histone deacetylase inhibitors (HDACi) are a class of compounds that inhibit histone deacetylase activity, which has been reported to be associated with depression; this article addresses the use of HDACi in preclinical studies, and their potential therapeutic role and limitations of use in depression.

This paper presents the preliminary investigation on chondromalacia patella at our department in recent years. A random cluster sampling survey covering 2743 normal persons was carried out. The prevalence rate is 36.2%. It was found that, applying transmission electron microscope and immunohistochemical methods on to cartilage tissues of the abnormal region, articular cartilage necrosis was in direct proportion with the abnormal pressure, while the restoration capability of local chondrocytes was in inverse proportion with pathological changes and the pressure. The chondromalacia patella was produced by repeated abnormal stress acting on the carilage. The stress derived from the uncongruency and the decreasing in the contact area of patellofemoral joint when the subluxation or tilt of patellae was caused by the abnormal anatomical and biomechanical relationship. The initial lesion was at the matrix of cartilage,the collagen network was disrupted, then proteoglycan was lost. The microenvironment of chondrocytes was changed with degradation of matrix. So the chon drocytes became degenerative and necrosis from superficial to deep layer, then feed back the matrix again. Finally, the total cartilage layer might disappear, and the bone under cartilage might proliferate. At late stage, the cartilage was completely destroyed and had no self-restorative ability. Therefore, early diagnosis and treatment are necessary. It is highly suggested axis radiograph of the knee with the tibiae tuberositas localization are helpful to early diagnosis. Furthermore, JKY-Muscle Rehabilitation Instrument is invented for non-operative therapy. It enhances muscle power by selective training of the vastus medialis muscle using electrical stimulator to relieve pain and correct subluxation of patella with 90% efficiency (63% of excellent-effective rate) . In late stage, patellofemoral replacement is recommended. The excellent-effective rate is 86.3%.

Aim To study the permeability of salidro-side(Sal)to the blood brain barrier(BBB)by high-performance liquid chromatography electrospray ioniza-tion tandem mass spectrometry(UPLC-ESI-MS-MS),and to explore the target and mechanism of Sal in the treatment of ischemic stroke(IS)by network pharma-cology,molecular docking technique and animal exper-iment.Methods UPLC-ESI-MS/MS was used to study the BBB penetration of Sal.Multiple databases were used to predict the target of Sal and the disease target of IS,GO and KEGG enrichment analysis were performed and verified by molecular docking technique and animal experiments.Results After Sal adminis-tration to normal rats and MCAO rats,Sal prototype and the metabolite tyrosol were detected in plasma and brain tissue of rats.A total of 191 targets were identi-fied by network pharmacology,the enrichment analysis of GO mainly involved in the biological processes of proteolysis and positive regulation of cell migration,and the analysis of KEGG pathway suggested that PI3K-Akt,MAPK,FOXO and other signaling path-ways played a key role in the treatment of IS by Sal The results of molecular docking showed that Sal had good binding ability with the core target of docking,and the results of animal experiments showed that Sal could significantly improve the neurologic impairment of MCAO rats,the number of Nissl-positive cells in is-chemic side significantly increased,and the expression of VEGF,EGFR and IGF1 increased,while the ex-pression of IL-6 and MMP9 was inhibited.Conclu-sions Sal is able to penetrate the BBB and enter the central nervous system for its pharmacological effects.Network pharmacology predicts the core targets of Sal in the treatment of IS,including VEGFA,EGFR,IL-6,MMP9,IGF1,CASP3,ALB,SRC.The effects of Sal on some core targets can be verified by animal ex-periments,to provide a reference for further study of the mechanism of Sal in the treatment of IS.

Hot-melt extrusion was applied to prepare mesoporous silica/ethylcellulose mini-matrix for sustained release, and fenofibrate was used as a model drug, ethylcellulose and xanthan gum were chosen as sustained-release agent and releasing moderator, respectively. This novel matrix obtained the controlled release ability by combining mesoporous silica drug delivery system and hot-melt extrusion technology. And mesoporous silica particle (SBA-15) was chosen as drug carrier to increase the dissolution rate of fenofibrate in this martix. Scanning electron microscope, transmission electron microscope, small angle X-ray powder diffraction and N2 adsorption-desorption were introduced to determine the particle morphology, particle size and pore structure of the synthesized SBA-15. The results showed that SBA-15 had a very high Brunauer-Emmett-Teller specific surface area, a narrow pore size distribution, large pore volume and a ordered two-dimensional hexagonal structure of p6mm symmetry. Differential scanning calorimetry and X-ray powder diffraction results demonstrated that fenofibrate dispersed in an amorphous state inside the pores of the mesoporous silica which contributed to the improvement in the dissolution rate. The drug release of mini-matrices was influenced by ethylcellulose viscosity grades and xanthan gum concentration, which increased with the increasing of xanthan gum concentration and decreasing of ethylcellulose viscosity. Mini-matrix containing 22% xanthan gum exhibited a good sustained release performance, and the drug release behavior followed the first-order kinetics.
Adsorption ; Calorimetry, Differential Scanning ; Cellulose ; analogs & derivatives ; Delayed-Action Preparations ; Drug Carriers ; chemistry ; Particle Size ; Porosity ; Powder Diffraction ; Powders ; Silicon Dioxide ; Solubility ; X-Ray Diffraction

OBJECTIVETo investigate the chemical constituents and establish a quantitative method of Mallotus apelta.

METHODCompound was isolated by silica gel, Sephadex LH-20 column chromatography and Pre-HPLC chromatography. Its structure was identified by physicochemical properties and spectral evidences. The content of M. apelta was determined by HPLC. Chromatographic conditions included Inertsil ODS-3 C18 column (4.6 mm x 150 mm, 5 microm) and the mobile phase consisting of a mixture of methanol-water (24:76). The detection wavelength was set at 335 nm.

RESULTOne compound was isolated from n-butanol extract of the M. apelta and its structure was identified as vicenin II. The calibration cure was linear in the range of 0.053-10.60 microg (r = 0.9999), the average recovery was 99. 32%, RSD 1.82% (n = 6).

CONCLUSIONThe compound was isolated from this plant for the first time. The method to determine the content of vicenin II by HPLC was established for the first time. This method is simple, accurate and reliable.

Apigenin ; analysis ; chemistry ; isolation & purification ; Chromatography, Gel ; Chromatography, High Pressure Liquid ; methods ; Glucosides ; analysis ; chemistry ; isolation & purification ; Mallotus Plant ; chemistry ; Plant Leaves ; chemistry ; Plants, Medicinal ; chemistry ; Reproducibility of Results

The clinical and hematologic features in 22 patients with metastatic carcinoma of bone marrow were observed and analyzed. Morphology of bone marrow cells, bone marrow biopsy and other accessory examinations were performed. The primary or cardinal symptoms of metastatic carcinoma of bone marrow included anemia (17 cases, 77.3%), ostealgia (10 cases, 45.5%), fever (8 cases, 36.4%), hemorrhage (4 cases, 18.2%) and complicated hemolytic anemia (4 cases, 18.2%). The primary carcinomas, diagnosed by pathologic and accessory examinations, include gastric carcinoma (6 cases, 27%), lung cancer (3 cases, 13.6%), ovarian cancer (2 cases, 9%), mammary cancer, prostatic carcinoma, osteocarcinoma and metastatic malignant melanoma (1 case, respectively), and unknown primary lesion (7 cases, 31.8%). The hematologic features were decrease of hemoglobin (17 cases, 77.3%) and blood plate count (16 cases, 72.7%), leukocytosis (11 cases, 50%), immature leukocytes (14 cases, 63.6%) and erythrocytes (9 cases, 40.9%) seen on the peripheral blood smear, and reticulocytosis (4 cases, 18.2%). Masses of metastatic carcinoma cells can be frequently seen at two sides and tail of bone marrow smear. Bone marrow biopsy of 8 cases demonstrated the infiltration of carcinoma cells with nest-like distribution in the bone marrow cavity. Examination of MRI in 6 case showed destruction of bone and corpus vertebra and abnormal signal focus. Bone marrow biopsy could contribute to improve the accuracy of diagnosis and determine the origin of primary carcinoma. MRI plays an important role in diagnosis of metastatic carcinoma in bone marrow.

Objective To explore surgical treatment of gliomas involving the motor eloquent area. Methods Twelve cases of gliomas involving precentral gyrus were underwent awake surgery procedures assis- ted with neuronavigation and brain functional mapping by cortical electrical stimulation.Results Eleven ca- ses acquired accurate location of both lesions and eloquent areas by neuronavigation and direct cortical stimula- tion.7 cases of motor cortices and 2 cases of motor speech centers were confirmed during the operation.Re- section,verified by postoperative MRI,was total in 8 cases (66.7%) and subtotal in 4 patients.Histological examination revealed an infiltrative glioma in all cases (8 low grade astrocytomas,2 high grade astrocytomas and 2 glioblastoma).Four patients had no postoperative deficit,while the other 8 patients were impaired, with,in all cases except one,complete recovery in 7 days to one month.Conclusion Direct cortical elec- trical stimulations and awake surgery offer a reliable,precise and safe method,allowing functional mapping es- pecially useful in case of infiltrative cerebral tumors in eloquent areas.This technique allows improvement in the quality of tumoral resection and concurrently a minimization of the risk of definitive postoperative neurologi- cal deficit.