Background:Clinical outcomes of undifferentiated arthritis (UA) are diverse,and only 40 ％ of patients with UA develop rheumatoid arthritis (RA) after 3 years.Discovering predictive markers at disease onset for further intervention is critical.Therefore,our objective was to analyze the clinical outcomes of UA and ascertain the predictors for RA development.Methods:We performed a prospective,multi-center study from January 2013 to October 2016 among Chinese patients diagnosed with UA in 22 tertiary-care hospitals.Clinical and serological parameters were obtained at recruitment.Follow-up was undertaken in all patients every 12 weeks for 2 years.Predictive factors of disease progression were identified using multivariate Cox proportional hazards regression.Results:A total of 234 patients were recruited in this study,and 17 (7.3％) patients failed to follow up during the study.Among the 217 patients who completed the study,83 (38.2％) patients went into remission.UA patients who developed RA had a higher rheumatoid factor (RF)-positivity (42.9％ vs.16.8％,x2=8.228,P=0.008),anti-cyclic citrullinated peptide (CCP) antibodypositivity (66.7％ vs.10.7％,x2 =43.897,P ＜ 0.001),and double-positivity rate of RF and anti-CCP antibody (38.1％ vs.4.1％,x2 =32.131,P ＜ 0.001) than those who did not.Anti-CCP antibody but not RF was an independent predictor for RA development (hazard ratio 18.017,95％ confidence interval:5.803-55.938;P ＜ 0.001).Conclusion:As an independent predictor of RA,anti-CCP antibody should be tested at disease onset in all patients with UA.

AIM: To evaluate the anatomic and visual outcomes of 25-gauge vitrectomies combined with air tamponade for the treatment of idiopathic macular hole (IMH).METHODS: Thirty eyes of 27 patients with IMH were included in this prospective interventional study.All patients underwent 25-gauge pars plana vitrectomy (PPV) combined with phacoemulsification and air tamponade.Best corrected visual acuity (BCVA, logMAR), perimetry and multifocal electroretinography (mfERG) were conducted before and after the operation.Anatomical changes were evaluated with optical coherence tomography (OCT).RESULTS: The macular holes closed successfully in 28 eyes after the primary vitrectomy.The mean BCVA improved from 0.72±0.22 logMAR preoperatively to 0.29±0.18 logMAR postoperatively (P<0.001).In the visual field of central 10°, the average mean deviation (MD) decreased from-3.59±1.83 dB preoperatively to-2.51±1.36 dB postoperatively (P<0.001) and the average pattern standard deviation (PSD) decreased from 1.86±0.68 dB preoperatively to 1.33±0.32 dB postoperatively (P=0.001).The retinal response densities of mfERG in the foveal and perifoveal area increased significantly, and implicit times of rings 4-6 prolonged significantly (P<0.05).The symptom duration and baseline N1 amplitude densities at ring 1 had a significant impact on postoperative BCVA (P<0.001, P=0.001, respectively).CONCLUSION: The 25-gauge PPV and air tamponade with 1 day prone positioning produce favorable anatomic and functional outcomes.

Objective To observe and analyze the clinical outcomes of perfluoropropane (C3 Fs) injection and laser photocoagulation on myopic foveoschisis.Methods A total of 14 patients (18 eyes) diagnosed as myopic foveoschisis were enrolled in this retrospective study.All patients received intraocular tamponade of 0.5-0.7 mL C3 F8,and after 1 week,underwent macular photocoagulation.These patients were given the best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) examination for central foveal thickness (CFT) and maximal macular thickness (MMT) before and after treatment.Results OCT examination showed that the mean CFT decreased significantly from (494.00 ±454.80) iμm before treatment to (193.61 ± 97.42) μm at the last follow-up,with statistical significance (P =0.01),and the mean MMT decreased from (687.33 ± 385.15)pμn to (331.06 ± 109.31)μm at the same duration,approaching significant difference (P =0.001).The foveoschisis healed completely and partially in 14 eyes at the last follow-up,the mean CFT decreased significantly from (567.36 ±493.01) μm before treatment to (171.43 ± 90.84) μm after treatment,with statistical significance (P =0.006),and the mean MMT decreased from (744.14 ± 417.38)μm to (303.86 ± 8.62)prn at the same duration,approaching significant difference (P =0.002).Patients' BCVA before treatment was (0.94 ± 0.39) logMAR,of which 13 eyes had BCVA ＜ 0.6 logMAR,and increased to (0.92 ± 0.36) logMAR at the last follow-up,with no significant difference (P =0.78).The foveoschisis healed completely and partially in 14 eyes,and the BCVA was (1.04 ± 0.37) logMAR before treatment,up to (0.90 ± 0.34) logMAR after treatment,and the difference was not statistically significant (P =0.16).At the last follow-up,the vision of 4 eyes was increased by 2 lines and above,and unchanged in 10 eyes.All patients had no visual symptoms such as dark spots and no increase in intraocular pressure after treatment.Conclusion Intraocular C3 F8 tamponade and macular photocoagulation can be an satisfying alternative treatment for patients with myopic foveoschisis.

OBJECTIVETo gain a better understanding of gene expression changes in the brain following microwave exposure in mice. This study hopes to reveal mechanisms contributing to microwave-induced learning and memory dysfunction.

METHODSMice were exposed to whole body 2100 MHz microwaves with specific absorption rates (SARs) of 0.45 W/kg, 1.8 W/kg, and 3.6 W/kg for 1 hour daily for 8 weeks. Differentially expressing genes in the brains were screened using high-density oligonucleotide arrays, with genes showing more significant differences further confirmed by RT-PCR.

RESULTSThe gene chip results demonstrated that 41 genes (0.45 W/kg group), 29 genes (1.8 W/kg group), and 219 genes (3.6 W/kg group) were differentially expressed. GO analysis revealed that these differentially expressed genes were primarily involved in metabolic processes, cellular metabolic processes, regulation of biological processes, macromolecular metabolic processes, biosynthetic processes, cellular protein metabolic processes, transport, developmental processes, cellular component organization, etc. KEGG pathway analysis showed that these genes are mainly involved in pathways related to ribosome, Alzheimer's disease, Parkinson's disease, long-term potentiation, Huntington's disease, and Neurotrophin signaling. Construction of a protein interaction network identified several important regulatory genes including synbindin (sbdn), Crystallin (CryaB), PPP1CA, Ywhaq, Psap, Psmb1, Pcbp2, etc., which play important roles in the processes of learning and memorye.

CONCLUSIONLong-term, low-level microwave exposure may inhibit learning and memory by affecting protein and energy metabolic processes and signaling pathways relating to neurological functions or diseases.

Animals ; Computational Biology ; Gene Expression ; radiation effects ; Learning ; Memory ; Mice ; Microwaves ; Reverse Transcriptase Polymerase Chain Reaction

Pregnane X receptor (PXR) is key transcription factors which mainly regulate the expression of CYP3A genes. At the molecular level, PXR has been revealed the protection mechanism of the body against xenochemicals and a major mode of the drug-drug interactions. Besides playing an important role in drug metabolism and interactions, PXR and its target genes also play an important role in maintaining normal physiological function and homeostasis. Therefore, it is necessary to study the regulation of PXR and its related pharmacological effects of TCM and natural products, and to provide new clues for the new pharmacological pathway.
Animals ; Drug Evaluation, Preclinical ; Drugs, Chinese Herbal ; pharmacology ; Gene Expression ; drug effects ; Humans ; Receptors, Steroid ; antagonists & inhibitors ; genetics ; metabolism

To study the effect of Siwu decoction on the function and expression of P-glycoprotein (P-gp) in Caco-2 cells. The Real-time quantitative poly-merase chain reaction (Q-PCR) was used to analyze the mRNA expression of MDR1 gene in Caco-2 cells. Flow cytometer was used to study the effect of Siwu decoction on the uptake of Rhodamine 123 in Caco-2 cells, in order to evaluate the efflux function of P-gp. Western blotting method was used to detect the effect of Siwu decoction on the P-gp protein expression of Caco-2 cells. Compared with the blank control group, after Caco-2 incubation with Siwu decoction at concentrations of 3.3, 5.0, 10.0 g x L(-1) for 24, 48, 72 h, the mRNA expression of MDR1 was up-regulated, suggesting the effect of Siwu decoction in inducing the expression of MDR1. After the administration with Siwu decoction in Caco-2 cells for 48 h, the uptake of Rhodamine 123 in Caco-2 cells decreased by respectively 16.6%, 22.1% (P < 0.05) and 45.4% (P < 0.01), indicating that the long-term administration of Siwu decoction can enhance the P-gp efflux function of Caco-2 cells. After the incubation of Caco-2 cells with Siwu decoction for 48 h, the P-gp protein expression on Caco-2 cell emebranes, demonstrating the effect of Siwu decoction in inducing the protein expression of P-gp.
ATP Binding Cassette Transporter, Sub-Family B ; genetics ; metabolism ; ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; metabolism ; Caco-2 Cells ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Up-Regulation ; drug effects

No abstract available.
Humans ; Interferon-gamma* ; Pityriasis Rosea*

In order to study effects of ginseng on the metabolism of drug belong to CYP3A4 substrate, screening of pregnane X receptor activation from ginsenosides was performed by reporter assay. Based on PXR-CYP3A stable translation cell lines, 13 ginsenosides were screened for pregnane X receptor activation by reporter assays, and RIF as the positive control. The effect of ginsenosides Rg1 onCYP3A4 mRNA expression was also investigated by RT-PCR. The PXR-CYP3A stable translation cell lines had good response to RIF, and the EC50 is 2.51 micro mol x L(-1). When the condition of final concentration was 10 micromol x L(-1), ginsenoside F2 and protopanaxatriol had moderate inductive effects on PXR. Panaxotriol, Rg2, pseudoginsenoside F11, Rg1, ginsenoside and Rb3 had inhibitory effects on PXR. Ginsenoside Rf1, Rg3, Rh2 and protopanaxdiol had no obvious effects on PXR. Rg1 down-regulated CYP3A4 mRNA expression in a concentration-dependent manner. Activation of pregnane X receptor by ginsenosides may influence the metabolism of drug belong to CYP3A4 substrate, and cause ginseng-drug interactions.
Cytochrome P-450 CYP3A ; genetics ; metabolism ; Drug Interactions ; Ginsenosides ; pharmacology ; Hep G2 Cells ; Humans ; RNA, Messenger ; metabolism ; Receptors, Steroid ; agonists ; antagonists & inhibitors ; genetics ; Sapogenins ; pharmacology ; Transfection

BACKGROUNDTraumatic brain injury (TBI) is a major cause of death and disability in children and young adults worldwide. Therefore, we investigated the role of AG490 in regulating brain oedema, expression of CD40 and neurological function after TBI.

METHODSSprague Dawley rats (n = 240) were randomly divided into a sham operation group, TBI+saline group and TBI+AG490 (JAK/STAT inhibitor) group. Members of each group were euthanized at 6, 12, 24 or 72 hours after injury. Neurological severity score (NSS) was used to evaluate the severity of neurological damage. Brain water was quantitated by wet/dry weight method. The expression of CD40 was assessed by flow cytometry.

RESULTSIn both the TBI+saline group and the TBI+AG490 group, the brain water content was elevated after TBI, reached a peak at 24-hour and remained high for the rest of the period investigated; the expression of CD40 reached a peak 24 hours after TBI; the NSS was elevated after TBI and then decreased after 6 hours. Elevations in the level of CD40, degree of brain edema and NSS after TBI were significantly reduced in TBI+AG490 group.

CONCLUSIONInhibition of the JAK/STAT signalling pathway reduces brain oedema, decreases the expression of CD40 and exerts neuroprotective effects after TBI.

Animals ; Brain Edema ; metabolism ; Brain Injuries ; drug therapy ; CD40 Antigens ; analysis ; Flow Cytometry ; Janus Kinases ; metabolism ; Male ; Neuroprotective Agents ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; STAT Transcription Factors ; metabolism ; Tyrphostins ; therapeutic use

BACKGROUNDHuman interleukin-10 (hIL-10) is a cytokine synthesis inhibitory factor, which is involved in various immune responses. The purpose of this study was to construct an adenoviral vector carrying the hIL-10 gene for expression of biologically active hIL-10 in rat bone marrow mesenchymal stem cells (rMSCs).

METHODSA pSNAV2.0-hIL10 plasmid was used as a template to obtain a hIL-10 cDNA fragment that was subcloned by restriction enzyme digestion and ligation into a pDC316-IRES-EGFP-lacZ alpha plasmid carrying an enhanced green fluorescent protein (EGFP) marker gene. The pDC316-hIL-10-IRES-EGFP plasmid was linearized by PmeI digestion and used to transfect HEK293 packaging cells using the adenovirus packaging system AdMax. Virus particles were amplified by repeatedly infecting HEK293 cells with the seed virus and then purified by ion exchange. After the number of virus particles and titer was determined, rMSCs were infected with the adenoviral vector. The infection rate was determined by fluorescence microscopy and flow cytometry, and hIL-10 protein expression in rMSCs was measured by Western blotting.

RESULTSThe virus particle concentration, OD260/280 value and virus titer of the amplified and purified recombinant adenovirus were 3.2 × 10(11) VP/ml, approximately 2.0, and 1.1 × 10(10) TCID50/ml, respectively. Bright green fluorescence was observed by fluorescence microscopy and flow cytometry in the recombinant adenovirus-infected rMSCs. GFP expression was considered the multiplicity of infection (MOI) and was time-dependent. The infection rate was 92.9% at 100 MOI.

CONCLUSIONSA bicistronic recombinant adenoviral vector for hIL-10 and EGFP gene expression were successfully constructed. The infection rate of rMSCs by the adenovirus was high (92.9% at 100 MOI) and the target gene hIL-10 was highly expressed in cells. The present study provides an experimental basis for further research of immunosuppressive therapy using hIL-10. The expression level of hIL-10 protein as detected by Western blotting was also MOI- and time-dependent.

Adenoviridae ; genetics ; Animals ; Cell Line ; Cells, Cultured ; Genetic Vectors ; genetics ; Green Fluorescent Proteins ; genetics ; metabolism ; Humans ; Interleukin-10 ; genetics ; metabolism ; Male ; Mesenchymal Stromal Cells ; metabolism ; Rats