Nitrogen-doped carbon dots derived from ellagic acid and L-tyrosine for photothermal anticancer and anti-inflammation.

Photothermal therapy (PTT) of tumor would ineluctably cause oxidative stress and related inflammation in adjacent normal tissues, leading to a discounted therapeutic outcome. To address this issue, herein an innovative therapeutic strategy that integrates photothermal anticancer and normal cell protection is developed. A new type of nitrogen-doped carbon dot (ET-CD) has been synthesized in one step by hydrothermal method using ellagic acid and L-tyrosine as reaction precursors. The as-prepared ET-CD exhibits high photothermal conversion efficiency and good photothermal stability. After intravenous injection, ET-CD can accumulate at the tumor site and the hyperthermia generated under near infrared laser irradiation effectively ablates tumor tissues, thereby significantly inhibiting tumor growth. Importantly, owing to the inherited antioxidant activity from ellagic acid, ET-CD can remove reactive oxygen and nitrogen species produced in the body and reduce the levels of inflammatory factors induced by oxidative stress, so as to alleviate the damage caused by heat-induced inflammation to normal cells and tissues while photothermal anticancer. These attractive features of ET-CD may open the exploration of innovative therapeutic strategies to promote the clinical application of PTT.

Glutathione-triggered release of SO2 gas to augment oxidative stress for enhanced chemodynamic and sonodynamic therapy.

Recently, gas therapy has emerged as a promising alternative treatment for deep-seated tumors. However, some challenges regarding insufficient or uncontrolled gas generation as well as unclear therapeutic mechanisms restrict its further clinical application. Herein, a well-designed nanoreactor based on intracellular glutathione (GSH)-triggered generation of sulfur dioxide (SO2) gas to augment oxidative stress has been developed for synergistic chemodynamic therapy (CDT)/sonodynamic therapy (SDT)/SO2 gas therapy. The nanoreactor (designed as CCM@FH-DNs) is constructed by employing iron-doped hollow mesoporous silica nanoparticles as carriers, the surface of which was modified with the SO2 prodrug 2,4-dinitrobenzenesulfonyl (DNs) and further coated with cancer cell membranes for homologous targeting. The CCM@FH-DNs can not only serve as a Fenton-like agent for CDT, but also as a sonosensitizer for SDT. Importantly, CCM@FH-DNs can release SO2 for SO2-mediated gas therapy. Both in vitro and in vivo evaluations demonstrate that the CCM@FH-DNs nanoreactor performs well in augmenting oxidative stress for SO2 gas therapy-enhanced CDT/SDT via GSH depletion and glutathione peroxidase-4 enzyme deactivation as well as superoxide dismutase inhibition. Moreover, the doped iron ions ensure that the CCM@FH-DNs nanoreactors enable magnetic resonance imaging-guided therapy. Such a GSH-triggered SO2 gas therapy-enhanced CDT/SDT strategy provides an intelligent paradigm for developing efficient tumor microenvironment-responsive treatments.

Supplementing a specific synbiotic suppressed the incidence of AOM/DSS-induced colorectal cancer in mice.

In this study, we evaluated the effect of a specific synbiotic on CAC (AOM/DSS-induced colitis-associated cancer). We confirmed that the synbiotic intervention was able to protect the intestinal barrier and inhibit CAC occurrence via upregulating tight junction proteins and anti-inflammatory cytokines, and downregulating pro-inflammatory cytokines. Moreover, the synbiotic significantly improved the disorder of the colonic microbiota of CAC mice, promoted the formation of SCFAs and the production of secondary bile acids, and alleviated the accumulation of primary bile acids in the CAC mice. Meanwhile, the synbiotic could significantly inhibit the abnormal activation of the intestinal Wnt/ß-catenin signaling pathway significantly related to IL-23. In a word, the synbiotic can inhibit the occurrence and development of colorectal tumors and it may be a functional food to prevent inflammation-related colon tumors, and the research also provided a theoretical basis for improving the intestinal microecological environment through diet therapy.

Reactive oxygen species nanoamplifiers with multi-enzymatic activities for enhanced tumor therapy.

The ingenious combination of nano-enzymes with multi-enzyme activities and therapeutic drugs that can promote reactive oxygen species (ROS) production in cancer cells will enhance the therapeutic efficacy of nanomedicines on malignant tumors by amplifying oxidative stress. Herein, PEGylated Ce-doped hollow mesoporous silica nanoparticles (Ce-HMSN-PEG) loaded with saikosaponin A (SSA) are elaborately constructed as a smart nanoplatform for improving the efficiency of tumor therapy. The carrier Ce-HMSN-PEG showed multi-enzyme activities due to the presence of mixed Ce3+/Ce4+ ions. In the tumor microenvironment, peroxidase-like Ce3+ ions convert endogenous H2O2 into highly toxic ˙OH for chemodynamic therapy, while Ce4+ ions not only show catalase-like activity to reduce tumor hypoxia but also exhibit glutathione (GSH) peroxidase-mimicking properties to effectively deplete GSH in tumor cells. Moreover, the loaded SSA can cause the enrichment of superoxide anions (˙O2-) and H2O2 within tumor cells by disrupting mitochondrial functions. By integrating the respective advantages of Ce-HMSN-PEG and SSA, the as-prepared SSA@Ce-HMSN-PEG nanoplatform can efficiently trigger cancer cell death and inhibit tumor growth via significantly enhanced ROS production. Therefore, this positive combination therapy strategy has a good application prospect for enhancing antitumor efficacy.

A 1-kb human CDCA8 promoter directs the spermatogonia-specific luciferase expression in adult testis.

Cell division cycle associated 8 (CDCA8) is a component of the chromosomal passenger complex and plays an essential role in mitosis, meiosis, cancer growth, and undifferentiated state of embryonic stem cells. However, its expression and role in adult tissues remain largely uncharacterized. Here, we studied the CDCA8 transcription in adult tissues by generating a transgenic mouse model, in which the luciferase was driven by a 1-kb human CDCA8 promoter. Our previous study showed that this 1-kb promoter was active enough to dictate reporter expression faithfully reflecting endogenous CDCA8 expression. Two founder mice carrying the transgene were identified. In vivo imaging and luciferase assays in tissue lysates revealed that CDCA8 promoter was highly activated and drove robust luciferase expression in testes. Subsequently, immunohistochemical and immunofluorescent staining showed that in adult transgenic testes, the expression of luciferase was restricted to a subset of spermatogonia that were located along the basement membrane and positive for the expression of GFRA1, a consensus marker for early undifferentiated spermatogonia. These findings for the first time indicate that the CDCA8 was transcriptionally activated in testis and thus may play a role in adult spermatogenesis. Moreover, the 1-kb CDCA8 promoter could be used for spermatogonia-specific gene expression in vivo and the transgenic lines constructed here could also be used for recovery of spermatogonia from adult testes.

An Ultrasound-Triggered Nanoplatform for Synergistic Sonodynamic-Nitric Oxide Therapy.

Ultrasound (US)-triggered sonodynamic therapy (SDT) has aroused intensive interest as a powerful alternative for cancer treatment in recent years due to its non-invasiveness and deep tissue penetration. However, the therapeutic effect of SDT alone is still limited by intrinsic hypoxia in solid tumors. Combined synergistic therapy strategies are highly desired for improving therapeutic efficiency. Herein, a rationally designed intelligent theranostic nanoplatform is developed for the enhancement of cancer treatment through synergistic SDT and nitric oxide (NO) therapy. This US-triggered nanoplatform is fabricated by integrating a sonosensitizer Rose Bengal (RB) and a NO donor (SNO) into manganese-doped hollow mesoporous silica nanoparticles (MH-SNO@RB). Impressively, the acidic and reducing tumor microenvironment accelerates the sustainable release of Mn ions from the framework, which facilitates the MH-SNO@RB to be used as a contrast agent for magnetic resonance imaging. More importantly, the reactive oxygen species (ROS) generated by RB and NO molecules released from SNO, which are simultaneously triggered by US, can react with each other to yield highly reactive peroxynitrite (ONOO-) ions for effective tumor inhibition both in vitro and in vivo. Furthermore, the nanoplatform demonstrates good hemocompatibility and histocompatibility. This study opens a new strategy for the full utilization of US and intelligent design avenues for high-performance cancer treatment.

Modulation of hypoxia and redox in the solid tumor microenvironment with a catalytic nanoplatform to enhance combinational chemodynamic/sonodynamic therapy.

The efficacy of reactive oxygen species-mediated therapy is generally limited by hypoxia and overexpressed glutathione (GSH) in the tumor microenvironment (TME). To address these issues, herein, a smart Mn3O4/OCN-PpIX@BSA nanoplatform is rationally developed to enhance the combinational therapeutic efficacy of chemodynamic therapy (CDT) and sonodynamic therapy (SDT) through TME modulation. For constructing the catalytic nanoplatform (Mn3O4/OCN-PpIX@BSA), Mn3O4 nanoparticles were grown in situ on oxidized g-C3N4 (OCN) nanosheets, and the as-prepared Mn3O4/OCN nano-hybrids were then successively loaded with protoporphyrin (PpIX) and coated with bovine serum albumin (BSA). The catalase-like Mn3O4 nanoparticles are able to effectively catalyze the overexpressed endogenous H2O2 to produce O2, which could relieve hypoxia and improve the therapeutic effect of combinational CDT/SDT. The decomposition of Mn3O4 by GSH enables the release of Mn2+ ions, which not only facilitates good T1/T2 dual-modal magnetic resonance imaging for tumor localization but also results in the depletion of GSH and the Mn2+-driven Fenton-like reaction, thus further amplifying the oxidative stress and achieving improved therapeutic efficacy. It is worth noting that the Mn3O4/OCN-PpIX@BSA nanocomposites exhibit minimal toxicity to normal tissues at therapeutic doses. These positive findings provide a new strategy for the convenient construction of TME-regulating smart theranostic nanoagents to improve the therapeutic outcomes towards malignant tumors effectively.

Sulourea-coordinated Pd nanocubes for NIR-responsive photothermal/H2S therapy of cancer.

BACKGROUND: Photothermal therapy (PTT) frequently cause thermal resistance in tumor cells by inducing the heat shock response, limiting its therapeutic effect. Hydrogen sulfide (H2S) with appropriate concentration can reverse the Warburg effect in cancer cells. The combination of PTT with H2S gas therapy is expected to achieve synergistic tumor treatment. METHODS: Here, sulourea (Su) is developed as a thermosensitive/hydrolysable H2S donor to be loaded into Pd nanocubes through in-depth coordination for construction of the Pd-Su nanomedicine for the first time to achieve photo-controlled H2S release, realizing the effective combination of photothermal therapy and H2S gas therapy. RESULTS: The Pd-Su nanomedicine shows a high Su loading capacity (85 mg g-1), a high near-infrared (NIR) photothermal conversion efficiency (69.4%), and NIR-controlled H2S release by the photothermal-triggered hydrolysis of Su. The combination of photothermal heating and H2S produces a strong synergetic effect by H2S-induced inhibition of heat shock response, thereby effectively inhibiting tumor growth. Moreover, high intratumoral accumulation of the Pd-Su nanomedicine after intravenous injection also enables photothermal/photoacoustic dual-mode imaging-guided tumor treatment. CONCLUSIONS: The proposed NIR-responsive heat/H2S release strategy provides a new approach for effective cancer therapy.

Gadolinium-doped hollow silica nanospheres loaded with curcumin for magnetic resonance imaging-guided synergistic cancer sonodynamic-chemotherapy.

Curcumin is a kind of anti-cancer chemotherapeutic drug and has been demonstrated to be able to produce reactive oxygen species (ROS) under the stimuli of ultrasound (US). Herein, gadolinium-doped hollow mesoporous silica nanospheres (Gd-HMSNs) loaded with curcumin (Cur) and conjugated with carboxymethyl dextran (CMD) have been facilely fabricated and applied for magnetic resonance imaging (MRI)-guided synergistic cancer sonodynamic-chemotherapy. The as-prepared multifunctional theranostic nanoplatform (Cur@Gd-HMSNs-CMD) shows high drug loading capacity, satisfactory biocompatibility, pH-responsive degradation, and US-triggered drug release. Due to the release of Gd3+ ions or oligomers during degradation, the nanoplatform Cur@Gd-HMSNs-CMD could serve as an effective contrast agent for T1-weighted MRI to guide cancer treatment. More significantly, in vivo experiments show that the Cur@Gd-HMSNs-CMD can efficiently inhibit the tumor growth by a high inhibition rate of ~85.6% under US irradiation, mainly resulting from the synergistic effect of sonodynamic-chemotherapy. This innovative "two-in-one" theranostic nanoplatform using a single drug provides a new strategy for developing "all-in-one" nanomaterials for combined cancer treatment.

Functionalized g-C3N4 nanosheets for potential use in magnetic resonance imaging-guided sonodynamic and nitric oxide combination therapy.

The oxygen consumption-induced hypoxia and the high concentration of glutathione in tumor microenvironment limit the treatment outcomes of sonodynamic therapy (SDT). SDT needs to be combined with other treatment modalities to achieve the desired therapeutic efficiency. In this study, an oxidized g-C3N4 (OCN) nanosheet-based theranostic nanoplatform is developed for sonodynamic and nitric oxide (NO) combination therapy of cancer. The OCN nanosheets are successively modified with amino-terminated 6-armed polyethylene glycol, chlorin e6, and Gd3+ ions, and then the as-prepared OCN-PEG-(Ce6-Gd3+) nanosheets are loaded with the NO donor N,N'-di-sec-butyl-N,N'-dinitroso-1,4-phenylenediamine (BNN6). Upon ultrasound (US) irradiation, the OCN-PEG-(Ce6-Gd3+)/BNN6 nanocomposite can induce the generation of reactive oxygen species (ROS) and simultaneously release NO molecules to effectively kill the cancer cells, thereby significantly suppressing the tumor growth. Moreover, a good in vivo T1-weighted magnetic resonance imaging (MRI) contrast effect is achieved after intravenous injection of OCN-PEG-(Ce6-Gd3+)/BNN6 due to remarkably enhanced contrast performance of the nanocomposite. Therefore, the OCN-PEG-(Ce6-Gd3+)/BNN6 formulation can serve as a promising theranostic agent for MRI-guided sonodynamic-NO combination therapy.

Tumor pH-Responsive Albumin/Polyaniline Assemblies for Amplified Photoacoustic Imaging and Augmented Photothermal Therapy.

Tumor-microenvironment-responsive theranostics have great potential for precision diagnosis and effective treatment of cancer. Polyaniline (PANI) is the first reported pH-responsive organic photothermal agent and is widely used as a theranostic agent. However, tumor pH-responsive PANI-based theranostic agents are not explored, mainly because the conversion from the emeraldine base (EB) to emeraldine salt (ES) state of PANI requires pH < 4, which is lower than tumor acidic microenvironment. Herein, a tumor pH-responsive PANI-based theranostic agent is designed and prepared for amplified photoacoustic imaging guided augmented photothermal therapy (PTT), through intermolecular acid-base reactions between carboxyl groups of bovine serum albumin (BSA) and imine moieties of PANI. The albumin/PANI assemblies (BSA-PANI) can convert from the EB to ES state at pH < 7, accompanied by the absorbance redshift from visible to near-infrared region. Both in vitro and in vivo results demonstrate that tumor acidic microenvironment can trigger both the photoacoustic imaging (PAI) signal amplification and the PTT efficacy enhancement of BSA-PANI assemblies. This work not only highlights that BSA-PANI assemblies overcome the limitation of low-pH protonation, but also provides a facile assembly strategy for a tumor pH-responsive PANI-based nanoplatform for cancer theranostics.

Proteomic analysis of microbial induced redox-dependent intestinal signaling.

Intestinal homeostasis is regulated in-part by reactive oxygen species (ROS) that are generated in the colonic mucosa following contact with certain lactobacilli. Mechanistically, ROS can modulate protein function through the oxidation of cysteine residues within proteins. Recent advances in cysteine labeling by the Isotope Coded Affinity Tags (ICATs) technique has facilitated the identification of cysteine thiol modifications in response to stimuli. Here, we used ICATs to map the redox protein network oxidized upon initial contact of the colonic mucosa with Lactobacillus rhamnosus GG (LGG). We detected significant LGG-specific redox changes in over 450 proteins, many of which are implicated to function in cellular processes such as endosomal trafficking, epithelial cell junctions, barrier integrity, and cytoskeleton maintenance and formation. We particularly noted the LGG-specific oxidation of Rac1, which is a pleiotropic regulator of many cellular processes. Together, these data reveal new insights into lactobacilli-induced and redox-dependent networks involved in intestinal homeostasis.

The risk of systemic lupus erythematosus associated with Epstein-Barr virus infection: a systematic review and meta-analysis.

Previous systematic reviews have found a higher sero-prevalence of EBV antibodies in SLE patients compared with controls. Because many studies have been published, there is a need to apply more precise systematic review methods. We examined the association between EBV and SLE patients by conducting a systematic review and meta-analysis of case-control studies that examined the prevalence of EBV antibodies and the DNA-positive rate. We searched the MEDLINE and EMBASE databases from 1966 to 2018 with no language restrictions. The Mantel-Haenszel odds ratios (OR) for EBV antibody sero-positivity were calculated, and meta-analyses were conducted. Quality assessment was performed using a modified version of the Newcastle-Ottawa scale, and 33 studies were included. Most studies found a higher sero-prevalence of VCA IgG and EA IgG in SLE patients compared with controls. Meta-analysis demonstrated a significantly higher OR for sero-positivity to VCA IgG and EA IgG for SLE cases (2.06 [95% confidence interval (CI) 1.30-3.26, p = 0.002] and 7.70, [95% CI 4.64-12.76, p < 0.001], respectively). The overall OR for the DNA-positive rate for SLE patients compared with controls was 3.86 (95% CI 1.52-9.83, p = 0.005). Other antibodies, i.e., VCA IgA/IgM, EBNA IgA, and EA IgA/IgM, also demonstrated a significant difference between SLE patients and controls. These findings support previous systematic reviews; however, publication bias cannot be excluded. The methodological conduct of studies could be improved, particularly when selecting controls and analyses of laboratory conduct.

Concentration effect on large scale synthesis of high quality small gold nanorods and their potential role in cancer theranostics.

Cancer theranostics agents, such as gold nanorods, represent great potential in cancer therapy. However, the big size and the low yield of the gold nanorods reported previously have limited their clinical translation. Therefore, it is significant to develop a new method to prepare the small gold nanorods (width <8 nm) at larger scale. In this report, a modified seedless method was proposed based on the effect of precursor concentration assisted synthesis of high quality small gold nanorods at large scale. The obtained small gold nanorods exhibit high quality and dimension of (18 ±â€¯5 nm) × (5 ±â€¯1 nm). After modified with biological compatibility reagents, the small gold nanorods behave excellent photoacoustic imaging and photo-thermal therapy ability. These results manifest that the obtained small gold nanorods not only realize the improvements of previously limitations, also are thus supposed to pave the way to cancer theranostics in clinic application.

Functionalized Cu3BiS3 nanoparticles for dual-modal imaging and targeted photothermal/photodynamic therapy.

Multifunctional nano-biomaterials with the integration of diagnostic and therapeutic functions have shown great promise in improving the efficacy of cancer therapy. Herein, a new nanoplatform based on functionalized Cu3BiS3 nanoparticles (NPs) is fabricated for tumour-targeted combination phototherapy. The as-synthesized hydrophobic Cu3BiS3 NPs are modified with DSPE-PEG/DSPE-PEG-NH2, followed by the conjugation of the photosensitizer chlorin e6 (Ce6) and the target ligand folic acid (FA). The introduced Ce6 can further form a chelate complex with Gd3+. The rationally designed Cu3BiS3-PEG-(Ce6-Gd3+)-FA NPs, which have high physiological stability and good biocompatibility, can specifically target FA-receptor over-expressed tumour cells. The Cu3BiS3-PEG-(Ce6-Gd3+)-FA NPs exhibit effective dual-modal CT and MR imaging in the xenografted HeLa tumours. Importantly, excellent in vivo anti-tumour effects have been achieved by synergistic photothermal/photodynamic therapy using the multifunctional NPs. We expect that this versatile nanoplatform will play a role in exploring precise cancer diagnosis and therapy.

Hydrophilic graphene oxide/bismuth selenide nanocomposites for CT imaging, photoacoustic imaging, and photothermal therapy.

A nanotheranostic agent has been fabricated by direct deposition of Bi2Se3 nanoparticles on graphene oxide (GO) in the presence of polyvinylpyrrolidone (PVP) using a one-pot solvothermal method. The resulting GO/Bi2Se3/PVP nanocomposites show low in vitro cytotoxicity, negligible hemolytic activity and little in vivo toxicity. GO/Bi2Se3/PVP nanocomposites could serve as an efficient bimodal contrast agent to simultaneously enhance X-ray computed tomography imaging and photoacoustic imaging in vivo. In addition, the nanocomposites exhibit significant photothermal cytotoxicity to cancer cells under 808 nm laser irradiation. After intratumoral or intravenous injection of the nanocomposites, irreversible photothermal ablation of tumors in the mouse model is successfully achieved by using 808 nm laser irradiation. All of the positive results highlight that the GO/Bi2Se3/PVP nanocomposites can be developed as a promising nanoplatform for efficient tumor theranostic applications.

The microenvironment of injured murine gut elicits a local pro-restitutive microbiota.

The mammalian intestine houses a complex microbial community, which influences normal epithelial growth and development, and is integral to the repair of damaged intestinal mucosa(1-3). Restitution of injured mucosa involves the recruitment of immune cells, epithelial migration and proliferation(4,5). Although microenvironmental alterations have been described in wound healing(6), a role for extrinsic influences, such as members of the microbiota, has not been reported. Here, we show that a distinct subpopulation of the normal mucosal-associated gut microbiota expands and preferentially colonizes sites of damaged murine mucosa in response to local environmental cues. Our results demonstrate that formyl peptide receptor 1 (FPR1) and neutrophilic NADPH oxidase (NOX2) are required for the rapid depletion of microenvironmental oxygen and compensatory responses, resulting in a dramatic enrichment of an anaerobic bacterial consortium. Furthermore, the dominant member of this wound-mucosa-associated microbiota, Akkermansia muciniphila (an anaerobic, mucinophilic gut symbiont(7,8)), stimulated proliferation and migration of enterocytes adjacent to the colonic wounds in a process involving FPR1 and intestinal epithelial-cell-specific NOX1-dependent redox signalling. These findings thus demonstrate how wound microenvironments induce the rapid emergence of 'probiont' species that contribute to enhanced repair of mucosal wounds. Such microorganisms could be exploited as potential therapeutics.

Graphene oxide/manganese ferrite nanohybrids for magnetic resonance imaging, photothermal therapy and drug delivery.

Superparamagnetic manganese ferrite (MnFe2O4) nanoparticles have been deposited on graphene oxide (GO) by the thermal decomposition of manganese (II) acetylacetonate and iron (III) acetylacetonate precursors in triethylene glycol. The resulting GO/MnFe2O4 nanohybrids show very low cytotoxicity, negligible hemolytic activity, and imperceptible in vivo toxicity. In vitro and in vivo magnetic resonance imaging experiments demonstrate that GO/MnFe2O4 nanohybrids could be used as an effective T2 contrast agent. The strong optical absorbance in the near-infrared (NIR) region and good photothermal stability of GO/MnFe2O4 nanohybrids result in the highly efficient photothermal ablation of cancer cells. GO/MnFe2O4 nanohybrids can be further loaded with doxorubicin (DOX) by π-π conjugate effect for chemotherapy. DOX release from GO/MnFe2O4 is significantly influenced by pH and can be triggered by NIR laser. The enhanced cancer cell killing by GO/MnFe2O4/DOX composites has been achieved when irradiated with near-infrared light, suggesting that the nanohybrids could deliver both DOX chemotherapy and photothermal therapy with a synergistic effect.

Characteristics of A20 gene polymorphisms and clinical significance in patients with rheumatoid arthritis.

BACKGROUND: There are a number of studies regarding to the susceptibility of A20 SNPs in rheumatoid arthritis (RA); however, a few of these studies have shown an association between polymorphisms in the A20 gene and RA risk in the Chinese population. The aim of this study was to investigate the characteristics of A20 gene polymorphisms, the association between polymorphisms and clinical significance in Chinese RA patients. METHODS: PCR and sequencing were used to identify A20 gene polymorphisms in peripheral blood mononuclear cells (PBMCs) (50 cases), synovial fluid (11 cases) from RA patients and PBMCs from 30 healthy individuals. Quantitative Real-time PCR (qRT-PCR) was used to analyze the A20 mRNA expression in 38 RA patients and 40 healthy individuals. Pearson's Chi square test and two independent-samples Wilcoxon tests were used for statistical analysis. RESULTS: Eight single nucleotide polymorphisms (SNPs) (rs5029937, rs3799491, rs598493, rs2307859, rs146534657, rs2230926, rs661561, and rs582757) were identified in PBMCs of RA patients. One new mutation (14284 T > A) was identified in synovial fluid mononuclear cells from one RA case. rs146534657 was identified for the first time in two RA cases. Patients with rs146534657 (12411 A > G, Asn102Ser) AG genotype or rs2230926 (12486 T > G, Phe127Cys) TG genotype had poor outcome. Significantly lower A20 mRNA expression was found in PBMCs from RA patients compared with healthy individuals (p < 0.001). There was a higher A20 mRNA expression in RA patients with rs2230926 TG genotype and rs146534657 AG genotype (11.56 ± 7.39) than patients with rs2230926 TT genotype and rs146534657 AA genotype (5.63 ± 4.37) (p = 0.031). CONCLUSION: Significantly lower A20 expression was found in RA patients. The polymorphisms of A20 were characterized in RA patients. We detected rs146534657 for the first time and identified a new A20 mutation (14284 T > A). A20 rs2230926 TG genotype and rs146534657 AG genotype may be related to poor outcome in RA patients.

[Value of dual-energy computed tomography in the diagnosis of gouty arthritis].

OBJECTIVE: To investigate the value of dual-energy computed tomography (DECT) in the diagnosis of gouty arthritis. METHODS: Sixty-one patients with gout, 30 with ankylosing spondylitis and 30 with rheumatoid arthritis were included in the study. DECT scans of the hands, wrists, elbows, feet, ankles, knees, lumbar, pelvis and sacroiliac joint were performed. For post-processing, a color-coding gout software protocol was used. The demographic data and blood uric acid levels were recorded. For 3 gout patients, the findings of puncture biopsy and DECT were compared. Ten gout patients with urate crystal deposition upon recruitment underwent DECT scans again after a 6-month urate-lowering therapy. RESULTS: The positivity rates of DECT scan differed significantly among the patients with gout, ankylosing spondylitis and rheumatoid arthritis [98.4% (60/61), 13.3% (4/30), and 6.7% (2/30), respectively; χ² =95.522, P<0.05). Of the 21 patients with acute gouty arthritis, 20 (95.2%) showed positive DECT finding, and all the 40 patients with chronic gouty arthritis showed positive findings. In the patients with patients with gout, ankylosing spondylitis and rheumatoid arthritis, the positivity rates of hyperuricemia were 97.3% (36/37), 44.4% (4/9), and 28.6% (2/7), respectively (χ² =24.197, P<0.05). A total of 344 urate deposition sites were detected in the gout patients, involving most commonly the first metatarsophalangeal joint (22.1%), the middle and distal end of the first phalanges of the toes (19.8%), the calcaneus (17.4%), and the inferior extremity of the tibia (13.4%). Seventeen and 5 urate deposition sites were found in ankylosing spondylitis patients and rheumatoid arthritis patients, respecitvely. The 10 gout patients receiving a 6-month urate-lowering therapy showed decreased urate deposition on DECT scan. CONCLUSIONS: DECT scan can detect urate deposition to allow differentiation diagnosis and follow-up in gout patients.