Objective To study the clinical profile of patients with central nervous system (CNS) involvement in relapsing polychondritis (RP).Methods Clinical data of five patients of RP with CNS lesions were collected,and compared with those from the literatures.T test and Fisher exact test were used for statistical analysis.Results Among 205 patients with RP in Peking Union Medical College Hospital,five cases (2.4％) had CNS damage.All 5 cases presented an active onset and occurred in the active phase of RP.All of them manifested as meningoencephalitis,complicating cranial neuropathies in 2 cases (2/5).Cerebrospinalfluid examination revealed non-specific meningeal inflammation,and magnetic resonance image (MRI) showed long T2 signals in brain lesions.Four patients (4/5) showed good response to high-dose glucocorticosteroid plus immunosuppressive agent combined therapy.The average age of our patients was younger than those in the literatures [(44± 14),(58± 11) years,respectively; t=2.547,P＜0.05],while other clinical features was not significantly different between the two groups.Conclusion CNS involvement is a rare condition in RP patients,and usually occurrs in the early course of active RP.Meningoencephalitis/ meningitis is the major clinical manifestations.MRI and cerebrospinal fluid examination may help to confirm the diagnosis.Treatment with corticosteroid and immunosuppressant can result in favorable response.

OBJECTIVETo observe the influence of endostar alone or in combination with cisplatin on tumor growth and metastasis, as well as the inhibition of angiogenesis and lymphangiogenesis in nude mouse models of human cervical cancer.

METHODSHeLa cells were inoculated subcutaneously into the hind flank region of female nu/mice to establish xenograft models. The nude mice were randomly divided into 5 groups: (1) sodium chloride (as control); (2) cisplatin alone; (3) endostar alone; (4) cisplatin plus endostar (10 mg/kg); (5) cisplatin plus endostar (20 mg/kg). The course of all the treatments lasted for 4 weeks. The tumor growth and lymph node metastasis were observed. Immunohistochemical staining was employed to detect the angiogenesis and lymphangiogenesis.

RESULTS(1) Either endostar alone or endostar with cisplatin inhibited the tumor growth significantly than cisplatin and NS (P < 0.05). (2) The rates of lymph node metastasis in the endostar (20 mg/kg) with cisplatin, the endostar (10 mg/kg) with cisplatin, the endostar, the cisplatin and the NS groups were 0 (0/8), 12.5% (1/8), 12.5% (1/8), 62.5% (5/8) and 75.0% (6/8) (P = 0.002), respectively. (3) The MVD of tumor tissue in these five groups were 10.88 +/- 1.38, 10.25 +/- 1.22, 10.83 +/- 2.29, 15.58 +/- 2.31 and 22.08 +/- 1.93, respectively (P < 0.05). The MLD were 5.00 +/- 0.63, 5.17 +/- 0.75, 6.00 +/- 0.63, 14.33 +/- 1.63 and 13.67 +/- 1.21, respectively (P < 0.05).

CONCLUSIONEndostar can reduce the tumor growth and metastasis by inhibiting angiogenesis and lymphangiogenesis in nude mouse model of human cervical cancer.

Angiogenesis Inhibitors ; pharmacology ; Animals ; Antineoplastic Agents ; pharmacology ; Cisplatin ; pharmacology ; Endostatins ; pharmacology ; Female ; HeLa Cells ; Humans ; Lymphangiogenesis ; drug effects ; Lymphatic Metastasis ; Lymphatic Vessels ; drug effects ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Microvessels ; drug effects ; Neoplasm Transplantation ; Neovascularization, Pathologic ; prevention & control ; Random Allocation ; Tumor Burden ; drug effects

Ranolazine and metabolites in dog urine were identified by LC-MS(n). Dog urine samples were collected after ig 30 mg x kg(-1) ranolazine, then the samples were enriched and purified through solid-phase extraction cartridge. The purified samples were analyzed by LC-MS(n). The possible metabolites were discovered by comparing the full scan and SIM chromatograms of the test samples with the corresponding blanks. Seventeen phase I metabolites and fourteen phase II metabolites were identified in dog urine. Three metabolites were identified by comparing with the control article. The metabolites were formed via the following metabolic pathways: O-demethylation, O-dearylation, hydroxylation, N-dealkylation, amide hydrolysis, glucuronidation and sulfation. The LC-MS(n) method is suitable for the rapid identification of drug and its metabolites in biologic samples.
Acetanilides ; administration & dosage ; metabolism ; urine ; Administration, Oral ; Animals ; Chromatography, Liquid ; Dogs ; Female ; Male ; Piperazines ; administration & dosage ; metabolism ; urine ; Ranolazine ; Solid Phase Extraction ; Spectrometry, Mass, Electrospray Ionization ; Tandem Mass Spectrometry

To identify the active constituents in vitro and blood-absorbed ingredients in vivo from Yin Chen Hao decoction provides scientific evidence for probing its prevention and treatment mechanism on acute liver injury. An ultrahigh performance liquid chromatography quadrupole-time of flight-mass spectrometry (UPLC-QTOF/MS) method was applied for analysis of Yin Chen Hao decoction and the serum samples of mice with con-A induced acute liver injury after preventive oral administration for 14 days (the use of all laboratory animals in this study was approved by the Ethics Committee of the Naval Medical University, 19YF1459400). A total of 90 chemical constituents were identified from Yin Chen Hao decoction, mainly were flavonoids, terpenoids, tannins, quinones. 5 prototype compounds were identified in the serum, including chrysophanol, deoxyrhapontin-8-O-gallate, mussaenosidic acid, herniarin, emodin. The established UPLC-QTOF/MS method could efficiently and sensitively identify the constituents in vitro and blood-absorbed ingredients of Yin Chen Hao decoction, primarily clarify the material basis of its hepatoprotective effect, and provided a scientific basis for the quality marker selection and the pharmacodynamic material basis research on the decoction.

Objective To study the relationship between cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) pathway and glutamine-stimulated insulin secretion.Methods In the prerequisite of the existence of glucose(0.25 mmol/L),the insulin secretion of βHC9 cells was stimulated with different concentrations of glutamine (0.0,0.5,1.0,2.0,5.0 mmol/L),then culture liquids were extracted and centrifugalized,and the insulin levels in the cell culture liquids and the cAMP levels in βHC9 cells were determined,so as to study the effects of glutamine stimulation on the insulin level in cell culture liquids and cAMP levels in βHC9 cells were assayed.Results In the prerequisite of the glucose existence,with the increasing of the concentrations of glutamine(0.0,0.5,1.0,2.0,5.0 mmol/L),the insulin levels[0.0 ng/(mL · million),19.1 ng/(mL · million),29.1 ng/(mL · million),30.1 ng/(mL · million),33.9 ng/(mL · million)] in cell culture liquids and the cAMP levels (0.0 pmol/million,40.0 pmol/million,51.5 pmol/million,52.5 pmol/million,61.3 pmoL/million) in βHC9 cells increased accordingly.Conclusion Glutamine has amplifying effect on glucose stimulated insulin secretion,such amplifying effect needs the existence of cAMP to be prerequisite.

Objective To investigate the effect of compound polyethylene glycol electrolyte powder (SF-PEG) and Magnesium Sulfate (MgSO4) on intestinal tract preparation in patients with constipation. Methods 135 cases of constipation patients who underwent colonoscopy were selected. They were divided into A, B and C groups, each with 45 cases.Group A and group B received oral SF-PEG and 219.2 g (2 000 ml) at 5:00 to 7:00. Group A take 50% MgSO450 ml at 9:00, and then took 250 ml warm water.Group B received the same dose of MgSO4 at 7:00. The two groups were examined by colonoscopy at 11:00. Group C received oral compound SF-PEG 219.2 g (2 000 ml) at 10:00 to 12:00, and then took 50% MgSO450 ml at 14:00, received colonoscopy at 16:00. According to the Boston bowel preparation scale (BBPS) score and parallel intraluminal bubble score. Determine the duration of bowel preparation process,and tolerance and adverse effects were recorded during bowel preparation. Results All patients completed bowel preparation and underwent a colonoscopy successfully. The scores of group A in BBPS were significantly higher than those in group B and group C (P < 0.05). In group A and group B, the score of parallel intraluminal bubble was lower than C, which was statistically significant (P < 0.05). The intestinal preparation time of A and B was less than that of group C, which was statistically significant (P < 0.05), and the tolerance of patients was higher in group A and group B than that in group C (P < 0.05). In adverse reactions, group A and group B were lower than those in group C (P < 0.05). Conclusions When taking the time (5:00 to 7:00), intermittent polyethylene glycol electrolyte powder and Magnesium Sulfate can shorten the bowel preparation time and improve the quality of bowel preparation in patients with constipation.

OBJECTIVETo explore the effects of p,p'-DDE and beta-BHC on the apoptosis of Sertoli cells in vitro via activation of Caspase.

METHODSSertoli cells were treated in vitro for 24 hours with a serial concentrations of p,p'-DDE (10, 30 and 50 micromol/L), beta-BHC (10, 30 and 50 micromol/L) and p,p'-DDE + beta-BHC (10, 30 and 50 micromol/L). The inhibitory group was first treated with 100 micromol/L Caspase-3 inhibitor Ac-DEVD-CHO treating for 2 hours before 50 micromol/L p, p'-DDE + 50 micromol/L beta-BHC 24 hours-treatment. The vitality of Sertoli cells was determined by MTT and the apoptosis rate was measured by AO/EB double fluorescence staining. The expressions of Caspase-3, Caspase-8 and Caspase-9 were determined by RT-PCR.

RESULTSAverage optical density (A) values were 0.498 +/- 0.039, 0.481 +/- 0.065, 0.397 +/- 0.032 and 0.286 +/- 0.049 in p,p'-DDE groups (10, 30, 50 and 70 micromol/L), and 0.518 +/- 0.103, 0.490 +/- 0.060, 0.454 +/- 0.054 and 0.302 +/- 0.030 in beta-BHC groups (10, 30, 50 and 70 micromol/L). In the mixture-treated groups (10, 30 and 50 micromol/L), the average A values were 0.483 +/- 0.048, 0.473 +/- 0.058 and 0.337 +/- 0.052. Compared with the solvent control group (0.527 +/- 0.022) , 50 micromol/L group of p, p'-DDE, beta-BHC or their mixture caused a significant decrease of Sertoli cell viability (t values were 4.599, 2.716, 6.537 respectively, P < 0.05). AO/EB double fluorescence staining analysis showed that apoptosis rates of Sertoli cells were significantly increased with all treated groups. The expressions of Caspase-3, Caspase-8 and Caspase-9 were upregulated as the concentrations of p,p'-DDE, beta-BHC and their mixture were increased.

CONCLUSIONp,p'-DDE, beta-BHC and their mixture could induce the apoptosis of Sertoli cells in vitro which was associated with activation of Caspase-3 mediated by cleavage of Caspase-8 and Caspase-9.

Animals ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Caspase 8 ; metabolism ; Caspase 9 ; metabolism ; Cells, Cultured ; Dichloroethylenes ; toxicity ; Lindane ; toxicity ; Male ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley ; Sertoli Cells ; drug effects ; metabolism

BACKGROUNDParaquat (PQ), an effective and widely used herbicide, has been proven to be safe when appropriately applied to eliminate weeds. However, PQ poisoning is an extremely frustrating clinical condition with a high mortality and with a lack of effective treatments in humans. PQ mainly accumulates in the lung, and the main molecular mechanism of PQ toxicity is based on redox cycling and intracellular oxidative stress generation. The aim of this study was to evaluate whether lysine acetylsalicylate (LAS) could protect the lung from the damage of PQ poisoning and to study the mechanisms of protection.

METHODSA model of PQ poisoning was established in 75 Sprague-Dawley rats by intragastric administration of 50 mg/kg PQ, followed by treatment with 200 mg/kg of LAS. The rats were randomly divided into sham, PQ, and PQ + LAS groups, with 25 in each group. We assessed and compared the malonaldehyde (MDA) content, superoxide dismutase activity (SOD), glutathion peroxidase (GSH-Px), and catalase (CAT) in serum and lung and the hydroxyproline (HYP) content, pathological changes, apoptosis and expression of Bcl-2/Bax protein in lung of rats on days 1, 3, 7, 14 and 21 after PQ poisoning and LAS treatment.

RESULTSCompared to the PQ group rats, early treatment with LAS reduced the MDA and HYP contents, and increased the SOD, GSH-Px, and CAT activities in the serum and lung on days 1, 3, 7, 14, and 21 after PQ poisoning (all P < 0.05). After early LAS treatment, the apoptotic rate and Bax expression of lung decreased, the Bcl-2 expression increased, and the Bcl-2/Bax ratio increased, compared to the PQ group rats. Furthermore, the pathological results of lungs revealed that after LAS treatment, early manifestations of PQ poisoning, such as hemorrhage, edema and inflammatory-cell infiltration, were improved to some degree, and collagen fibers in the pulmonary interstitium were also obviously reduced.

CONCLUSIONIn this rat model of PQ poisoning, LAS effectively ameliorated the lung injury induced by PQ, possibly through antioxidation, anti-fibrosis, anti-apoptosis, and anticoagulation.

Animals ; Antioxidants ; metabolism ; Aspirin ; analogs & derivatives ; standards ; therapeutic use ; Catalase ; metabolism ; Glutathione Peroxidase ; metabolism ; Lung ; drug effects ; metabolism ; Lung Injury ; chemically induced ; drug therapy ; metabolism ; Lysine ; analogs & derivatives ; standards ; therapeutic use ; Male ; Malondialdehyde ; metabolism ; Paraquat ; toxicity ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism

OBJECTIVETo study the action mechanism of p,p'-DDE and/or beta-BHC on JNK and MAPK signal transduction pathways in rat Sertoli cells in vitro.

METHODSWe cultured the Sertoli cells isolated from rat testicular tissues for 2 days in vitro, divided them into a control group incubated with DMSO and 3 case groups exposed to p,p'-DDE and / or beta-BHC at the final concentration of 10, 30, 50 micromol/L for 24 hours, and then detected the expression levels of JNK and c-jun mRNA by two-step RT-PCR.

RESULTSTwenty-four hours after p,p'-DDE treatment, the grayscale values of JNK mRNA were 0.068 +/- 0.001, 0.164 +/- 0.002, 0.207 +/- 0.006 and 0.499 +/- 0.017, and those of c-jun mRNA were 0.122 +/- 0.002, 0.157 +/- 0.006, 0.218 +/- 0.007 and 0.289 +/- 0.004 respectively in the DMSO control and the 10, 30 and 50 micromol/L groups. The expressions of JNK and c-jun mRNA were elevated with increased concentration of p,p'-DDE, with significant differences between the control and the case groups (P < 0.05), and they were also significantly upregulated in the beta-BHC and p,p'-DDE + beta-BHC groups in a dose-dependent manner. The grayscale values of JNK mRNA in the p,p'-DDE, beta-BHC and p,p'-DDE + beta-BHC groups at the concentration of 10 micromol/L were 0.164 +/- 0.002, 0.149 +/- 0.003 and 0.178 +/- 0.004, and those of c-jun mRNA were 0.157 +/- 0.006, 0.131 +/- 0.004 and 0.172 +/- 0.002, respectively, both significantly higher in the combination group than in the former two (P < 0.05). And the same was the case with the 30 and 50 micromol/L concentrations.

CONCLUSIONBoth p,p'-DDE and beta-BHC can enhance the expressions of JNK and c-jun in Sertoli cells, and their combination can produce even more obvious effect.

Animals ; Cells, Cultured ; Dichlorodiphenyl Dichloroethylene ; chemistry ; toxicity ; Dose-Response Relationship, Drug ; Gene Expression ; drug effects ; Lindane ; chemistry ; toxicity ; MAP Kinase Signaling System ; drug effects ; Male ; Proto-Oncogene Proteins c-jun ; genetics ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Sertoli Cells ; cytology ; drug effects ; metabolism

OBJECTIVETo collect background information on drug resistance mutations in treatment-naïve HIV-1 infected individuals in Liaoning Province.

METHODSSamples from 91 antiretroviral therapy-naïve patients were collected. The entire protease gene and 1-290 amino acids of the reverse transcriptase gene were amplified by nested PCR from provirus DNA and sequenced. The results were analyzed with HIVdb-Drug Resistance Algorithm, and genotypic resistance mutations were determined to particular anti-HIV drugs.

RESULTSTotally 91 sequences were obtained, 3 of which displayed M46I mutations in the protease gene. Minor resistance mutation rate to protease inhibitors was 100%, including types of L63P (60.4%), V77I (60.4%), M36I/V (31.9%), A71V/T (22.0%), L10I (8.8%), and K20R (6.6%). Only one sequence carried reverse transcriptase related resistance mutations M184I.

CONCLUSIONSAbout 4.4% of HIV-1 infected individuals in Liaoning Province carried strains with drug resistance mutations. Most treatment-naïve HIV-1 infected individuals in Liaoning Province were sensitive to the currently available antiviral medicines, but antiviral treatment must be in accordance with the strict procedures to keep better adherence and avoid the prevalence of drug-resistant strains.

Adult ; China ; epidemiology ; Drug Resistance, Viral ; genetics ; Female ; HIV Infections ; drug therapy ; epidemiology ; HIV Protease ; genetics ; HIV Reverse Transcriptase ; genetics ; HIV-1 ; genetics ; Humans ; Male ; Molecular Epidemiology ; Mutation ; Sequence Analysis, DNA