A 54-year-old man was admitted to the Department of Rheumatology in Peking Union Medic.al College Hospital due to polyarthritis.back pain and multiple subcutaneous masses.He had symmetrical polyarthritis at onset.which was diagnosed as theumatoid arthritis.His follow-up and treatment were irregular.Back pain and multiple subcutaneous masses developed 2 year ago.Erythrocyte sedimentation rate and C-reac.tive protein were elevated.Rheumatoid fac.tor and Anti-cylic citrullinated peptide antibody were positive.No evidence of infection or malignancy was detected.Chest CT suggested pulmonary fibrosis and osteolytic lesions of stemum.Spinal MRI showed paravertebral soft tissue.Biopsy of the soft tissue suggested the pathologic.al finding of a theumatoid nodule.The patient was diagnosed as theumatoid arthritis complic.ated with multiple theumatoid bursal cysts.Combination therapy of methylprednisolone (40mg/d) and cyclophosphamide (0.4g/w) lead to a rapid improvement of clinical symptoms and laboratory parameters.The patient was still in remission at 6-month follow-up.

OBJECTIVE:To virtually screen lignanoid compounds with inhibitory effect of histone deacetylase(HDAC)by vir-tual screening method. METHODS:Using“lignanoid”as keyword,requiring CNKI,VIP,PubMed and other database,lignanoid compounds were collected as ligand to establish ligand base, histone deacetylase receptor HDAC2 (PDB code:4LXZ) and HDAC8 (PDB code:1T69) were selected from PDB database,and then ligands and 3D active site of receptors were docked by SYBYL-X 2.0 software. The affinity of receptors to ligand was reflected by total score. RESULTS:345 lignanoid compounds, 4LXZ and 1T69 primary ligand were used to establish ligand base which included 347 ligands. Ligands No.275,271,110,200, 056,258,181,129,037,270,187 were demonstrated good affinity with receptors HDAC2 and HDAC8. Ligands and receptors residue were docked via hydrogen bond. CONCLUSIONS:Lignanoid compounds have inhibitory effect on HDAC;virtual screen-ing method is effective in natural product activity prediction,which can provide quick access to and theoretical guidance for new pharmacological studies of lignanoid compounds.

Objective To investigate the epidemiological features of 937 patients wounded in China Wenchuan earthquake. Methods An analysis was done on 937 patients treated in the city of Deyang in aspects fo their gender,age,injury causes,wound sites,complications and misdiagnosis.Results There were more wounded females than males,with ratio of male to female of 1:1.12.The main injury causes were crush injury and falling injury.The most frequent injury sites include head,chest,ankle and foot,tibia and fibula,spine and hip.The rate of misdiagnosis was as high as 15.5%,mainly brain injuries and chest iniuries. Conclusion The main causes are crush iniury and falling in-jury.Lower limb fractures account for the most.While close brain and thoracic injuries are likely to be misdiagnosed.

In recent years, layer-by-layer self-assembly (LbL) has developed rapidly. It has been widely used in various industries such as medicine and metallurgy because of its simplicity, flexibility and controllability. In the study of drug delivery system, hollow microcapsules constructed by LbL method as drug carrier have great advantages in drug release, circulation in vivo and bioavailability, providing a technical platform for targeted drug release. In this paper, we summarize the types of film-forming materials and the driving force used in LbL technology, the way of loading drug into hollow micro capsule, and the variety of loaded drugs. We focus on the release mechanism, its evaluation and safety evaluation of self-assembled film as drug carrier in vivo and in vitro. The review shows the great application prospect of LbL technology in the field of drug delivery.

The pharmacokinetics of 6beta-naltrexol (6beta-NOL) following single intramuscular administration and multiple intramuscular injection once per day for seven days was studied in 4 Beagle dogs. Plasma concentration of 6beta-NOL in dogs was analyzed by a combination of high performance liquid chromatography (HPLC) and electrochemical detection with naloxone (NLX) as internal standard. After single intramuscular injection of 0.2 mg x kg(-1) 6beta-NOL, the plasma concentration-time curve of the drug was found to fit to a two compartment model with first-order absorption. The main parameters of single dosing were as follows: t1/2alpha was (0.26 +/- 0.23) h, t1/2beta was (4.77 +/- 1.65) h, C(max) was (81.65 +/- 5.61) ng x mL(-1), t(peak) was (0.27 +/- 0.07) h, CL(s) was (1.20 +/- 0.06) L x kg(-1) x h(-1), V/F(c) was (1.94 +/- 0.15) L x kg(-1), and AUC(0-t) was (166.82 +/- 7.68) ng x h x mL(-1), separately. After multiple intramuscular injection of 0.2 mg x kg(-1) 6beta-NOL once per day for seven days, the plasma concentration-time curve of the drug fitted to a two compartment model with first-order absorption too. The main parameters of the last dosing were as follows: t1/2alpha was (0.19 +/- 0.18) h, t1/2beta was (5.79 +/- 1.50) h, C(max) was (79.82 +/- 10.5) ng x mL(-1), t(peak) was (0.18 +/- 0.08) h, CL(s) was (1.12 +/- 0.07) L x kg(-1) x h(-1), V/F(c) was (2.10 +/- 0.27) L x kg(-1), and AUC(0-t) was (173.23 +/- 9.49) ng x h x mL(-1), separately. The difference of the parameters between the first and the last dosing was not significant, showing that the plasma kinetics of 6beta-naltrexol was not changed after multiple administrations. In the course of multiple administration, the peak and valley concentration of plasma 6beta-naltrexol were (79.03 +/- 10.3) and (1.50 +/- 0.93) ng x mL(-1), respectively. No clear adverse events were noted during this study. These results showed that plasma 6beta-naltrexol fits to a two compartment model with first-order absorption in dog after intramuscular administration and their pharmacokinetic parameters were reported. There was no remarkable change on plasma pharmacokinetics of 6beta-naltrexol after multiple intramuscular administrations.
Animals ; Chromatography, High Pressure Liquid ; Dogs ; Half-Life ; Injections, Intramuscular ; Male ; Naltrexone ; administration & dosage ; analogs & derivatives ; pharmacokinetics

OBJECTIVETo investigate the relationship between serum alpha-fetoprotein (AFP) variant levels in patients with hepatocellular carcinoma (HCC) and cancer cells disseminating through blood.

METHODSSerum AFP variant levels were measured by crossed immunoaffino-electrophoresis in the presence of lectin before initial surgical treatment in HCC patients. Circulating tumor cells were simultaneously detected in pre-operative blood samples using reverse transcription-polymerase chain reaction (RT-PCR) for AFP mRNA.

RESULTSForty-six HCC patients with serum AFP positive were studied. Serum AFP variant level > or 20% was showed in 37 patients, among whom there were 22 (59.5%) showing AFP mRNA positive. In contrast, the positive AFP mRNA expression was only observed in 2 out of 9 patients (22.2%) with AFP variant level<20% (x(2)=4.02, P<0.05).

CONCLUSIONIn hepatocellular carcinoma patients, increased AFP variant levels are associated with a haematogenous spread of tumor cells.

Adult ; Aged ; Carcinoma, Hepatocellular ; blood ; Female ; Humans ; Liver Neoplasms ; blood ; Male ; Middle Aged ; RNA, Messenger ; blood ; Reverse Transcriptase Polymerase Chain Reaction ; alpha-Fetoproteins ; analysis ; genetics

OBJECTIVETo investigate the specific cytotoxity of tumor infiltrating lymphocytes (TIL) transfected with chimeric T cell receptor (CTCR) on cells which express KDR.

METHODSA recombinant retroviral plasmid (pMSCVneo-Vhgamma) was constructed by cloning VEGF121-hinger-FcRgamma (Vhgamma) into retroviral vector pMSCVneo. After packaging by PT67, the virus with high titer was used to infect TIL isolated from liver cancer tissues, and then MSCVneo-Vhgamma-TIL was generated. TIL infected with MSCVneo was used as a control. The cytotoxicty of the transgenic TIL on NIH3T3 and HepG2 expressing no KDR and on ECV304 and A375 expressing KDR was detected with MTT colorimetric assay.

RESULTSThe sequences of VEGF121 and hinger-FcRgamma were different from those reported, but the deduced amino sequences were identical to the reported ones. The cytotoxity of TIL infected with MSCVneo on target cell was similar to that of the control TIL; both only had mild cytotoxity on cancer cell line. No significant cytotoxity was found in TIL infected with MSCVneo-cTCR on NIH3T3, but its cytotoxity on ECV304 was significant. The cytotoxity on HepG2 was similar to that of MSCVneo-TIL and uninfected TIL, but cytotoxity on A375 was significantly higher.

CONCLUSIONChimeric T cell receptor permanently grafts TIL cell with predefined new specificity. TIL expressing Vhgamma can selectively recognize and kill vascular endothelial cell and tumor cells which express VEGF receptor KDR.

Animals ; Cytotoxicity, Immunologic ; Humans ; Lymphocytes, Tumor-Infiltrating ; immunology ; Mice ; NIH 3T3 Cells ; Plasmids ; Receptors, Antigen, T-Cell ; physiology ; Retroviridae ; genetics ; Transfection ; Vascular Endothelial Growth Factor Receptor-2 ; physiology

Objective To investigate the effects of regular and irregular mandatory treadmill running (TR) on learning and memory abilities,stress response,survival and maturation of newborn neurons in dentate area of C57 mice. Methods Forty-eight male C57BL/6 mice were randomly divided into regular running group (n=16,definite time and quantity), irregular running group (n=16,definite time and different quantities) and sedentary group (n=16).Injection of bromodeoxyuridine (BrdU,50 mg/kg) was given intraperitoneally to mice from the 1st d to the 7th d of exercise,and then,these mice were subjected to a 4-wk TR training course or sedentary exercise.Double irnmunofluorescence labeling was employed to observe the effect of TR on survival and maturation of newborn neurons. Mice were trained on the Morris water maze to test the abilities of learning and memory. Corticosterone (CORT).level in the venous blood was measured with a radioimmunoassay kit. Results As compared with that in mice of the irregular running group and sedentary group,significant decrease of latency was noted in mice of the regular running group on the 1st, 3rd, 4th and 5th d of place navigation test (P＜0.05). As compared with that in mice of the sedentary group, significant decrease of latency was noted in mice of the irregular running group and regular running group on the 2nd d of place navigation test (P＜0.05),while no significant difference of that was noted between mice of the irregular running group and regular running group (P＞0.05).The platform was removed for a 60-s probe test 4 h after the last trial to test the recall ability, and the times of staying in the target zone in each group were regular running group＞irregular running group＞control group, and significant difference was noted between each 2 groups (P＜0.05). The numbers of double immunofluorescence labeled cells in the dentate gyrus were counted as regular running group＞irregular running group＞control group, and significant difference was noted between each 2 groups (P＜0.05). The serum CORT level was measured as regular running group＜irregular running group＜control group, and significant difference was noted between each 2 groups (P＜0.05). Conclusion Mandatory treadmill running could improve the learning and memory abilities,which may be related to the increment of survival and maturation of neural precursor cells,and decreased level of serum CORT; and the effect of regular mandatory treadmill running is better than that of irregular mandatory treadmill running.

This study is to identify Chinese medicinal materials Rhizoma et Radix Heraclei, Angelicae Sinensis, Radix Angelicae Pubescentis and Rhizoma et Radix Notopterygii based on ITS2 and its secondary structure. Total 26 ITS sequences of 7 species were downloaded from GenBank, the ITS2 sequences were annotated by HMMer method. The NJ phylogenetic tree was built by MEGA software, the intraspecific and interspecific K2P genetic distance were analyzed by MEGA as well. The ITS2 secondary structures of all taxa were predicted by ITS2 database. Sequence matrix of primary structure and secondary structure was aligned by 4Sale software. And the profile neighbor joining (PNJ) phylogenetic tree was constructed via the the ProfDistS software based on the distance method. The results show that, the average interspecific genetic distance was far greater than the average intraspecific genetic distance, an obvious barcoding gap was noted among all taxa; NJ tree showed that all species were clustered into seperate branches; each species had different secondary structures; the PNJ tree showed higher resolution than NJ tree. Therefore, ITS2 is suggested to be used as a barcode for distinguishing the original plants of Rhizoma et Radix Heraclei, Radix Angelicae Sinensis, Radix Angelicae Pubescentis and Rhizoma et Radix Notopterygii in this study, this provides some scientific basis for classification and accurate identification of these Chinese medicinal materials.

Placenta, an important organ, mediates the exchange of nutrients and metabolites between mother and fetus. The transporters, including ATP-binding cassette (ABC) transporters and solute carrier (SLC), expressed in the syncytiotrophoblast play a vital role in substance exchange. Some transporters, such as organic cation transporters (OCTs) and organic anion transporters (OATs), mediate the uptake of endogenous substances and drugs. Some transporters, such as P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) and multidrug resistance-associated proteins (MRPs), can excrete their substrates from the syncytiotrophoblast to the maternal circulation. However, the expression and activity of these transporters are not uniform throughout the gestation period, since they can be affected by physiological and pathological changes during pregnancy or drugs. Thus, an understanding of the role of placental transporters and the variation in their expression and activity in response to physiological and pathological changes is essential for efficient and safe therapy during pregnancy, and it also has important value in the development of drug treatment in pregnancy.