sis were given.

BACKGROUND: Results from clinical trials suggested that clopidogrel and ticlopidine had side effects of granulopenia, and aspirin could inhibit endothelial progenitor cell proliferation. There is no report of effects of these drugs on human bone marrow mesenchymal stem cells (hBMSCs) in stem cell transplantation. OBJECTIVE: To investigate the effects of antiplatelet drugs including clopidogrel, ticlopidine and aspirin on hBMSC proliferation and secretion. DESIGN, TIME AND SETTING: The cytology in vitro observation was performed at the Laboratory of Toxicology, Shanghai Municipal Center for Disease Control and Prevention from March to December 2006.MATERIALS: The second passage of hBMSCs was kindly donated from Shanghai Tissue Engineering Research & Development Center, Shanghai Ninth People's Hospital. Clopidogrel (Lot number J20040006) and ticlopidine (Lot number H19980186) were obtained from Hangzhou Sanofi-Synthelabo Minsheng Pharmaceutical CO., Ltd. Aspirin (Lot number 20050059) was obtained from Bayer Vital GmbH. METHODS: The standard culture medium consisted of DMEM-LG, 10% heat-inactivated FBS, 100 U/mL penicillin and 100 μg/mL streptomycin. After being cultured in vitro expanded out to passage 6, hBMSCs were treated with antiplatelet drugs of different concentrations and compared with control group. MAIN OUTCOME MEASURES: Cell proliferation was assessed by 3- (4, 5-dimethylthiazol -2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay, level of vascular endothelial growth factor (VEGF) of culture medium was detected by enzyme-linked immunoadsordent assay (ELISA), and surface antigens of hBMSCs were analyzed by the flow cytometry. RESULTS: A570 values of hBMSCs treated by clopidogrel or ticlopidine of 0.02,0.1,0.4,2,10,40 μmol/L were higher than control group (P < 0.01), while A570 values of aspirin group of 60, 600, 2 000 μmol/L were lower than control group(P < 0.05). Antiplatelet drugs had no obvious effect on cell surface antigens(CD34, CD105, CD106)expressed by hBMSCs. Treated by high dose clopidogrel or ticlopidine (40 μmol/L), VEGF level from hMSCs was lower than that of control group(P < 0.01), but VEGF level of low dose (0.02 μmol/L) ticlopidine group was higher than control group(P < 0.01), and there was no significantly difference of VEGF level among low dose clopidogrel group (0.02 μmol/L), aspirin group (5, 2 000 μmol/L), and control group(P > 0.05). CONCLUSION: Clopidogrel and ticlopidine improve proliferation of hBMSCs, but aspirin inhibits proliferation of hBMSCs. High dose of clopidogrel and ticlopidine suppress VEGF secretion of hBMSCs, while low dose of ticlopidine promote it. Antiplatelet drugs have no obvious effect on hBMSCs differentiation.

Triptolide (TPT), an active compound extracted from Chinese herb Tripterygium wilfordii , has been used in therapy of rheumatoid arthritis (RA). In this study, after synovial fibroblasts from rheumatoid arthritis (RASFs) were treated with TPT, we investigated its effect on the differentiation of Th17 cells. Firstly, the mRNA level of cyclooxygenase (COX) wad detected by qRT-PCR and the protein level of prostaglandin E2 (PGE2) was tested by ELISA in RASFs treated with different concentrations (0, 10, 50, 100 nmol L-1 ) of TPT. Then after TPT pre-treated RASFs and RA CD4 + T cells wer e co-cultured for 3 days in the presence or absence of PGE2, IL-17 and IFN-gamma production in CD4 T cell subsets were detected by flow cytometry. The results showed TPT decreased the mRNA experssion of COX2 and the secretion of PGE2 in RASFs in a dose-dependent manner(P <0. 05). We further found that differentiation of Thl7 cells was downregulated in a dose-dependent manner, and exogenous PGE2 could reverse the inhibition of Th17 cell differentiation(P <0. 05). Taken together, our results demonstrated that TPT inhibited the mRNA level of COX2 and the secretion of PGE2 in RASFs, which partly led to impaired Th17 cell differentiation in vitro.
Arthritis, Rheumatoid ; drug therapy ; enzymology ; immunology ; Cell Differentiation ; drug effects ; Cell Line ; Cyclooxygenase 2 ; genetics ; metabolism ; Dinoprostone ; metabolism ; Diterpenes ; pharmacology ; Epoxy Compounds ; pharmacology ; Fibroblasts ; drug effects ; immunology ; Gene Expression Regulation, Enzymologic ; drug effects ; Humans ; Middle Aged ; Phenanthrenes ; pharmacology ; Synovial Fluid ; drug effects ; Th17 Cells ; drug effects ; pathology

OBJECTIVETo study the relationship between Chinese medical syndrome types and metabolomics of non-small cell lung cancer (NSCLC) patients.

METHODSTotally 120 NSCLC patients were assigned to asthenia syndrome group and sthenia syndrome group, 60 in each group. Meanwhile, 60 cases of benign pulmonary nodules in physical examinations were recruited as the control group. Tumor tissues or benign pulmonary nodules tissues were obtained by thoracoscope. Changes of their metabolites were observed using gas chromatography-mass spectrometry (GC-MS). Their differences were studied using principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA). ROC curve analysis was performed in different metabolic compounds of sthenia and asthenia syndromes groups. The area under the curve (AUC) was calculated to evaluate the sensitivity of diagnosing syndrome types.

RESULTSCompared with the control group, difference existed in 16 compounds. Of them , contents of citric acid, pyruvic acid, alanine, choline phosphate, glycerol phosphate choline, linoleic acid, oleic acid, lactic acid, inositol were more in the two tumors group than in the control group. Difference existed in 10 compounds between the sthenia syndrome group and the asthenia syndrome group. Of them, citric acid, pyruvic acid, alanine, choline phosphate, glycerol phosphate choline, lactic acid, and inositol were more in the asthenia syndrome group than in the sthenia syndrome group. Contents of valine, glucose, and glutamine were more in the sthenia syndrome group than in the asthenia syndrome group. ROC curve analyses of different compounds indicated that AUC of lactic acid and glucose was more than 0.8 (P < 0.01); AUC of inositol, choline phosphate, and glycerol phosphate choline was more than 0.7 (P < 0.01); AUC of valine, citric acid, glutamine, alanine, and pyruvic acid was more than 0.6 (P < 0.05).

CONCLUSIONSThere existed certain correlation between CM syndrome types and metabolomics of lung cancer. Lactic acid, glucose, inositol, choline phosphate, glycerol phosphate choline, valine, citric acid, glutamine, alanine, pyruvic acid were sensitive diagnostic compounds, and the first four kinds were most sensitive compounds.

Asian Continental Ancestry Group ; Carcinoma, Non-Small-Cell Lung ; metabolism ; Gas Chromatography-Mass Spectrometry ; Humans ; Lactic Acid ; Least-Squares Analysis ; Metabolomics ; methods ; Principal Component Analysis ; Pyruvic Acid

Adult ; Aged ; Aged, 80 and over ; Biliary Tract Neoplasms ; complications ; Cholangitis ; etiology ; Cholestasis ; etiology ; therapy ; Drainage ; adverse effects ; Female ; Hepatic Encephalopathy ; etiology ; Humans ; Intraoperative Period ; Jaundice, Obstructive ; etiology ; therapy ; Liver Neoplasms ; complications ; Male ; Middle Aged ; Pancreatitis ; etiology ; Stents ; adverse effects

Tumor has long been a hard-nut problem in the world medical field. The effect of the conventional drugs is very limited because of the intervention of multiple micro-environmental factors during the occurrence and progression of tumors. With the characteristics of high efficiency, low toxicity and multi-targets synergistic effect, the long-circulating tumor targeted compound preparations show its unique advantages in improving tumor microenvironment and enhancing the therapeutic effect of treatment, thus it has gradually become a hotspot of studies both at home and abroad. Through consulting a great number of professional literatures at home and abroad in recent years, the authors summarized the current studies in vitro and in vive on long-circulating tumor targeted compound preparations in different carriers, in the expectation of providing new ideas and methods for the development of long-circulating tumor targeted compound preparations.
Animals ; Antineoplastic Agents ; blood ; chemistry ; therapeutic use ; Drug Compounding ; methods ; Humans ; Molecular Targeted Therapy ; methods ; Neoplasms ; blood ; drug therapy

In order to solve the problems of erratic drug absorption and low bioavailability after oral administration for poorly-water soluble drugs due to low solubility, a series of novel pharmaceutical dosage forms as solid dispersion, liposome, microemulsion, vesicle, cyclodextrin inclusion complexes and drug nanocrystal have been developed in recent years. Among which drug nanocrystal attracts more attentions for its simpler preparation method, higher drug loading and easier manufacturing technology in the design of dosage forms suitable for different administration routes. In this paper, the nanocrystals of the poorly-water soluble drugs prepared based on bottom-up and top-down technologies were introduced. The characteristics and applications of the nanocrystal-based dosage forms as suspension, tablet and capsule were also introduced and carefully evaluated with the focus on their pharmacokinetics, pharmacodynamics and tissue targeted drug distribution after delivery by oral administration, intravenous injection and pulmonary inhalation. The advantages of drug nanocrystals in their therapeutics effects over the bulk drugs were discussed together with the inherent mechanism. Finally, the problems existing in basic research and scaled-up manufacture of drug nanocrystal as well as the possible ways of solution were listed out so as to make the nanocrystal-based preparations exert their maximum therapeutic effect after clinical application.

Objective To explore the value of multivoxel 1H-MRS in the differential diagnosis of corpus callosum lesions.Methods 17 patients with corpus callosum lesions confirmed by clinical or pathological method underwent MRS examination.These patients included 2 cases of lymphoma,4 cases of Marchiafava-Bignami disease,3 cases of glioma, 7 cases of infarction,and 1 case of multiple sclerosis.MRS features of lesions were analyzed.Results 2 cases with corpus callosum lymphoma revealed significantly increased Cho peak, decreased Cr and NAA peak,towering Lip peak.Among 4 cases with Marchiafava-Bignami diseases, 2 cases revealed increased Cho/Cr and decreased NAA/Cr,1 case showed normal,1 case revealed inverted Lac peak.For 3 cases with corpus callosum glioma,NAA peak decreased or disappeared,and Cho peak increased in varying degrees.7 cases with corpus callosum infarction revealed significant inverted Lac peak, and NAA peak decreased in varying degrees.1 case of multiple sclerosis revealed increased Cho peak,decreased NAA peak,and inverted Lac peak during acute period with enhancement,while these features returned normal during inactive period.Conclusion Multivoxel 1H-MRS plays an important role in the differential diagnosis of corpus callosum lesions.

Objective To investigate prognostic factors for bloodstream infection in adult patients. Methods Clinical data of 131 adult patients with positive blood cultures during January 2002 to December 2003 in the Hospital were collected and 91 cases of them were retrospectively analyzed to understand their pathogen species and prognostic factors for it.Results Blood samples from 91 patients were cultured positive,53 cases(58.2%)with gram-negative bacteria mainly including Escherichia coli,Salmonella spp. and Klebsiella pneumoniae,28(30.8%)with gram-positive bacteria,mainly including Staphylococcus aureus and coagnlase-negative Staphylococci,eight(8.8%)with fungi and two(2.2%)with multiple infections.Case fatality ratio in this group of patients with septicemia was 30.8% during their hospitalization,and that in those with Pseudomonas aeruginosa,Staphylococcus aureus,Stenotrophomonas maltophilia and E.coli with extended-spectrum beta-lactamase was over 50%.Case fatality ratio was associated with severity of sepsis(OR=1.15)and inappropriately initial empirical treatment with antibiotics (OR=6.77).Conclusions Pathogen causing bloodstream infection in adults were mainly gram-negative bacteria and severity of infection and inappropriate initial antibiotics treatment could increase their fatality.

Abstract: Objective　To analyze the clinical characteristics of Chlamydia psittaci pneumonia and improve the diagnosis and treatment skills of clinicians on this disease. Methods The clinical data of thirty-nine Chlamydia psittaci pneumonia cases detected by metagenomic next-generation sequencing (mNGS) from September 2020 to January 2022 at the Affiliated Hospital of Southwest Medical University were retrospectively analyzed. Results There was a history of poultry exposure in 89.7%(35 cases) of the patients. The most common clinical manifestations were high fever (92.3%, 36), cough (76.9%,30), muscle soreness (48.7%,19), headache (38.5%,15), etc. Laboratory examinations showed 76.9% of patients had a normal leukocyte count, and 76.9% had decreased lymphocyte count, often accompanied by elevated C-reactive protein (100%), procalcitonin (97.4%), interleukin-6 (95.8%), interleukin-10 (95.8%), alanine aminotransferase (74.4%), and aspartate aminotransferase (84.6%). Univariate analysis indicated that there were statistically significant differences in the levels of aspartate transaminase, blood urea nitrogen, C-reactive protein, and procalcitonin between severe pneumonia patients and non-severe pneumonia patients（P<0.05）. Multivariate logistic regression analysis showed that an elevated blood urea nitrogen (OR=4.899) had guiding significance for predicting the occurrence of severe pneumonia. Bronchoscopy examination showed no abnormalities in 53.6% of the patients. The imaging manifestations of pulmonary lesions were mainly lobar pneumonia (61.5%) and air bronchograms (94.9%). Therapeutically, it was sensitive to tetracyclines, macrocyclic lactones, and fluoroquinolones. A total of 84.6%(33 cases) of the patients were cured and discharged from the hospital at the end of the treatment. Conclusion Chlamydia psittaci pneumonia is a zoonotic disease that can be detected by mNGS. An elevated blood urea nitrogen level has guiding significance for predicting the occurrence of severe pneumonia. Empirically-selected regimens based on doxycycline are effective for the treatment of Chlamydia psittaci pneumonia.