Construction of Zwitterionic Coatings with Lubricating and Antiadhesive Properties for Invisible Aligner Applications.

Invisible aligners have been widely used in orthodontic treatment but still present issues with plaque formation and oral mucosa abrasion, which can lead to complicated oral diseases. To address these issues, hydrophilic poly(sulfobetaine methacrylate) (polySBMA) coatings with lubricating, antifouling, and antiadhesive properties have been developed on the aligner materials (i.e., polyethylene terephthalate glycol, PETG) via a simple and feasible glycidyl methacrylate (GMA)-assisted coating strategy. Poly(GMA-co-SBMA) is grafted onto the aminated PETG surface via the ring-opening reaction of GMA (i.e., "grafting to" approach to obtain G-co-S coating), or a polySBMA layer is formed on the GMA-grafted PETG surface via free radical polymerization (i.e., "grafting from" approach to obtain G-g-S coating). The G-co-S and G-g-S coatings significantly reduce the friction coefficient of PETG surface. Protein adsorption, bacterial adhesion, and biofilm formation on the G-co-S- and G-g-S-coated surfaces are significantly inhibited. The performance of the coatings remains stable after storage in air or artificial saliva for 2 weeks. Both coatings demonstrate good biocompatibility in vitro and is not caused irritation to the oral mucosa of rats in vivo over 2 weeks. This study proposes a promising strategy for the development of invisible aligners with improved performance, which is beneficial for oral health treatment.

Mild hyperthermia enhanced synergistic uric acid degradation and multiple ROS elimination for an effective acute gout therapy.

BACKGROUND: Acute gouty is caused by the excessive accumulation of Monosodium Urate (MSU) crystals within various parts of the body, which leads to a deterioration of the local microenvironment. This degradation is marked by elevated levels of uric acid (UA), increased reactive oxygen species (ROS) production, hypoxic conditions, an upsurge in pro-inflammatory mediators, and mitochondrial dysfunction. RESULTS: In this study, we developed a multifunctional nanoparticle of polydopamine-platinum (PDA@Pt) to combat acute gout by leveraging mild hyperthermia to synergistically enhance UA degradation and anti-inflammatory effect. Herein, PDA acts as a foundational template that facilitates the growth of a Pt shell on the surface of its nanospheres, leading to the formation of the PDA@Pt nanomedicine. Within this therapeutic agent, the Pt nanoparticle catalyzes the decomposition of UA and actively breaks down endogenous hydrogen peroxide (H2O2) to produce O2, which helps to alleviate hypoxic conditions. Concurrently, the PDA component possesses exceptional capacity for ROS scavenging. Most significantly, Both PDA and Pt shell exhibit absorption in the Near-Infrared-II (NIR-II) region, which not only endow PDA@Pt with superior photothermal conversion efficiency for effective photothermal therapy (PTT) but also substantially enhances the nanomedicine's capacity for UA degradation, O2 production and ROS scavenging enzymatic activities. This photothermally-enhanced approach effectively facilitates the repair of mitochondrial damage and downregulates the NF-κB signaling pathway to inhibit the expression of pro-inflammatory cytokines. CONCLUSIONS: The multifunctional nanomedicine PDA@Pt exhibits exceptional efficacy in UA reduction and anti-inflammatory effects, presenting a promising potential therapeutic strategy for the management of acute gout.

The complex of tannic acid and cetylpyridinium chloride: An antibacterial and stain-removal cleaner for aligners.

INTRODUCTION: Effective aligner hygiene is recognized as an important part of orthodontic treatments and oral hygiene. However, there is no effective cleansing method for removable aligners. METHODS: In this study, we incorporated tannic acid (TA) with cetylpyridinium chloride (CPC) to develop the TA-CPC complex. The antibacterial properties of 15.8 mg/mL TA-CPC against Escherichia coli and Staphylococcus aureus were evaluated in vitro, which were compared with 5.1 mg/mL TA, 10.7 mg/mL CPC, a commercial denture cleansing solution (YA; 15 mg/mL), and water. As for the assessment of stain-removal ability, the aligners stained by coffee were soaked in cleansing solutions, and the color changes (ΔE∗) were calculated on the basis of the CIE L∗a∗b∗ color system, and the National Bureau of Standards system was used for the clinical interpretation of the color change. Atomic force microscope examination, tensile property assessment, and wavelength dispersive x-ray fluorescence analysis were performed to investigate the material compatibility of TA-CPC, and Cell Counting Kit-8 assay and live/dead assay were used to test the cytotoxicity of TA-CPC. RESULTS: The results showed that TA-CPC had a positive zeta-potential, and cation-π interaction changed the chemical environments of the phenyl group in TA-CPC, resulting in greater inhibition zones of S. aureus and E. coli than other cleaners. The quantification of the biofilm biomass and the fluorescent intensities also reflected that the TA-CPC solution exhibited better antibacterial ability. As for the ability of stain removal, ΔE∗ value of group TA-CPC was 2.84 ± 0.55, whereas those of stained aligners immersed with deionized distilled water, TA, YA, and CPC were 10.26 ± 0.04, 9.54 ± 0.24, 5.93 ± 0.36, and 4.69 ± 0.35, respectively. The visual inspection and National Bureau of Standards ratings also showed that the color of stained aligners cleansed by TA-CPC was much lighter than those of the other groups. Meanwhile, TA-CPC had good compatibility with the aligner material and cells. CONCLUSIONS: TA-CPC is a promising strategy to inhibit the formation of biofilms and remove the stains on the aligners safely, which may disinfect the aligners to improve oral health and help keep the transparent appearances of aligners without impacting the morphology and mechanical properties.

miR-20a-5p regulated SMAD6 to inhibit chondrogenesis of hDPSCs.

OBJECTIVES: Chondrogenic differentiation of human dental pulp stem cells (hDPSCs) is highly promising for cartilage repair. The specific mechanism, however, still needs to be explicated. MATERIALS AND METHODS: In this study, we isolated hDPSCs and transfected cells with lentiviruses containing an over-expression, knock-down, or negative control of miR-20a-5p. Three-D pellet cultures of hDPSCs were used for the chondrogenic induction. Following the pellet culture period, chondrogenesis was assessed by histological and immunohistochemical analysis and expression of chondrogenic-related genes. Dual-luciferase report assay was performed to determine potential targeted genes of miR-20a-5p, and the phosphorylation levels of P65 and IκBα were explored. Animal experiments were performed to determine the effect of miR-20a-5p on cartilage regeneration. RESULTS: miR-20a-5p was showed to repress the expression of SMAD6 to inhibit the chondrogenic differentiation of hDPSCs. Accordingly, the knock-down of miR-20a-5p promoted cartilage regeneration in the osteochondral defects of rats. Mechanically, it is indicated that NF-κB signaling is the potential down-stream network of miR-20a-5p/Smad6 crosstalk during chondrogenic differentiation. CONCLUSIONS: miR-20a-5p could target SMAD6 to activate NF-κB signaling pathway, and thus inhibit chondrogenesis of hDPSCs, which provided promising therapeutic target for cartilage defects clinically.

Down-regulation of hsa-circ-0107593 promotes osteogenic differentiation of hADSCs via miR-20a-5p/SMAD6 signaling.

OBJECTIVES: Increasing evidence indicated circRNAs were involved in stem cells osteogenesis differentiation. Herein, we aimed to clarify the role of hsa-circ-0107593 during the osteogenesis process of human adipose-derived stem cells (hADSCs) and the underlying mechanisms. METHODS: The ring structure of hsa-circ-0107593 was confirmed using RNase R treatment and Sanger sequencing. Nucleoplasmic separation and fluorescence in situ hybridization detected hsa-circ-0107593 distribution. Lentivirus and siRNA were used to modulate the expression of hsa-circ-0107593, and the binding relationship between hsa-circ-0107593 and miR-20a-5p was verified by luciferase assay and RNA immunoprecipitation. We detected the osteogenic activity of hADSCs through alkaline phosphatase staining, alizarin red S staining, real-time polymerase chain reaction (RT-PCR), western blot, and cellular immunofluorescence experiment. In vivo, micro-computed tomography was performed to analyze bone formation around skull defect. RESULTS: RT-PCR results exhibited that hsa-circ-0107593 was downregulated while miR-20a-5p was upregulated during hADSCs osteogenesis. In vivo and in vitro experiments results indicated that knocking down hsa-circ-0107593 promoted the osteogenic differentiation of hADSCs, while overexpression of hsa-circ-0107593 showed an inhibitory effect on hADSCs osteogenic differentiation. In vitro experiment results showed hsa-circ-0107593 acted as a hADSCs osteogenic differentiation negative factor for it inhibited the suppressing effect of miR-20a-5p on SMAD6. CONCLUSION: Knocking down hsa-circ-0107593 acts as a positive factor of the osteogenic differentiation of hADSCs via miR-20a-5p/SMAD6 signaling.

CircRNA-miRNA networks in regulating bone disease.

Circular RNA (circRNA) is a class of endogenous noncoding RNA (ncRNA), presenting as a special covalent closed loop without a 5' cap or 3' tail, maintaining resistance to RNA exonuclease and keeping high stability. Although lowly expressed in most situations, circRNA makes an active difference in regulating physiological or pathological processes by modulating gene expression by regulation of transcription, protein, and miRNA functions through various mechanisms in particular tissues. Recent studies have demonstrated the roles of the miRNA-circRNA network in the development of several bone diseases such as osteoporosis, a multiple-mechanism disease resulting from defective bone quality and low bone mass, osteoarthritis, whose main pathomechanism is inflammation and articular cartilage degradation, as well as osteosarcoma, known as one of the most common bone cancers. However, the specific mechanism of how circRNA along with miRNA influences those diseases is not well documented, showing potential for the development of new therapies for those bone diseases.

Rational Design of Quinoxalinone-Based Red-Emitting Probes for High-Affinity and Long-Term Visualizing Amyloid-ß In Vivo.

Alzheimer's disease (AD) is a progressive neurodegenerative disease with insidious onset, and the deposition of amyloid-ß (Aß) is believed to be one of the main cause. Fluorescence imaging is a promising technique for this task, but the Aß gold standard probe ThT developed based on this still has shortcomings. The development of a new fluorescent probe to detect Aß plaques is thought to be essential. Herein, a series of red to near-infrared emitting fluorescent probes QNO-ADs with newly quinoxalinone skeleton are designed to detect Aß plaques. They all demonstrate excellent optical properties and high binding affinity (∼Kd = 20 nM) to Aß aggregates. As the most outstanding candidate, QNO-AD-3 shows significant signal-to-noise (S/N) ratio at the level of in vitro binding studies, and the brilliant fluorescence staining results in favor of grasping the approximate distribution of Aß plaques in the brain slice. In vivo Aß plaques imaging suggests that QNO-AD-3 can cross the BBB and have a long retention time in the brain with low biological toxicity. In addition, the results of docking theoretical calculation also provide some references for the design of Aß probe. Overall, given the high affinity of QNO-AD-3 and the ability to monitor Aß plaques for a long time that is not common now, we believe QNO-AD-3 will be an effective tool for an Aß-related matrix and AD disease research in the future.

High-Dimensional Bell Test without Detection Loophole.

Violation of Bell's inequalities shows strong conflict between quantum mechanics and local realism. Loophole-free Bell tests not only deepen understanding of quantum mechanics, but are also important foundations for device-independent (DI) tasks in quantum information. High-dimensional quantum systems offer a significant advantage over qubits for closing the detection loophole. In the symmetric scenario, a detection efficiency as low as 61.8% can be tolerated using four-dimensional states and a four-setting Bell inequality [Phys. Rev. Lett. 104, 060401 (2010)PRLTAO0031-900710.1103/PhysRevLett.104.060401]. For the first time, we show that four-dimensional entangled photons violate a Bell inequality while closing the detection loophole in experiment. The detection efficiency of the four-dimensional entangled source is about 71.7%, and the fidelity of the state is 0.995±0.001. Combining the technique of multicore fibers, the realization of loophole-free high-dimensional Bell tests and high-dimensional quantum DI technologies are promising.

Entanglement Swapping and Quantum Correlations via Symmetric Joint Measurements.

We use hyperentanglement to experimentally realize deterministic entanglement swapping based on quantum elegant joint measurements. These are joint projections of two qubits onto highly symmetric, isoentangled bases. We report measurement fidelities no smaller than 97.4%. We showcase the applications of these measurements by using the entanglement swapping procedure to demonstrate quantum correlations in the form of proof-of-principle violations of both bilocal Bell inequalities and more stringent correlation criteria corresponding to full network nonlocality. Our results are a foray into entangled measurements and nonlocality beyond the paradigmatic Bell state measurement and they show the relevance of more general measurements in entanglement swapping scenarios.

mTOR regulates cocaine-induced behavioural sensitization through the SynDIG1-GluA2 interaction in the nucleus accumbens.

Behavioral sensitization is a progressive increase in locomotor or stereotypic behaviours in response to drugs. It is believed to contribute to the reinforcing properties of drugs and to play an important role in relapse after cessation of drug abuse. However, the mechanism underlying this behaviour remains poorly understood. In this study, we showed that mTOR signaling was activated during the expression of behavioral sensitization to cocaine and that intraperitoneal or intra-nucleus accumbens (NAc) treatment with rapamycin, a specific mTOR inhibitor, attenuated cocaine-induced behavioural sensitization. Cocaine significantly modified brain lipid profiles in the NAc of cocaine-sensitized mice and markedly elevated the levels of phosphatidylinositol-4-monophosphates (PIPs), including PIP, PIP2, and PIP3. The behavioural effect of cocaine was attenuated by intra-NAc administration of LY294002, an AKT-specific inhibitor, suggesting that PIPs may contribute to mTOR activation in response to cocaine. An RNA-sequencing analysis of the downstream effectors of mTOR signalling revealed that cocaine significantly decreased the expression of SynDIG1, a known substrate of mTOR signalling, and decreased the surface expression of GluA2. In contrast, AAV-mediated SynDIG1 overexpression in NAc attenuated intracellular GluA2 internalization by promoting the SynDIG1-GluA2 interaction, thus maintaining GluA2 surface expression and repressing cocaine-induced behaviours. In conclusion, NAc SynDIG1 may play a negative regulatory role in cocaine-induced behavioural sensitization by regulating synaptic surface expression of GluA2.

Hyaluronan injection versus oral glucosamine and diclofenac in the treatment of temporomandibular joint osteoarthritis.

OBJECTIVES: This study was aimed to compare the effects of 4 biweekly hyaluronan (HA) injection with glucosamine and diclofenac oral administration on TMJ OA patients. MATERIALS AND METHODS: This retrospective cohort study included TMJ OA patients who had the treatment of 4 biweekly HA injection (group HA) or oral glucosamine hydrochloride for 3 months and diclofenac sodium for 2 weeks (group G/D), and had complete data at first-visit, 3 months, 6 months, and 12 months. Clinical signs and symptoms were scored by anamnestic dysfunction index (Ai) and clinical dysfunction index (Di), and condylar bone changes were evaluated by CBCT scoring system. RESULTS: We included 22 patients in group HA and 20 patients in group G/D. After HA injection, Ai was decreased from 4.3 to 1.6(CI [- 4.0, - 1.4]) at 3-month follow-up, which was smaller than that in group G/D significantly. Di in group HA was declined significantly from 8.1 at first-visit to 3.6 at 3-month follow-up, while Di in group G/D scarcely changed until at 6- and 12-month follow-up. Neither HA injection nor oral glucosamine/diclofenac showed positive effect on the bone of TMJs during follow-ups with statistical significance. CONCLUSIONS: HA injection alleviated signs and symptoms of TMJ OA rapidly and presented superior clinical effects over oral glucosamine with diclofenac. However, both treatments did not limit the bone destruction of TMJs significantly. CLINICAL RELEVANCE: This cohort study provides knowledge on the symptom relief and bone changes of TMJ OA patients when treated with HA injection or glucosamine and diclofenac oral administration.

Long-Distance Entanglement Purification for Quantum Communication.

High-quality long-distance entanglement is essential for both quantum communication and scalable quantum networks. Entanglement purification is to distill high-quality entanglement from low-quality entanglement in a noisy environment and it plays a key role in quantum repeaters. The previous significant entanglement purification experiments require two pairs of low-quality entangled states and were demonstrated in tabletop. Here we propose and report a high-efficiency and long-distance entanglement purification using only one pair of hyperentangled state. We also demonstrate its practical application in entanglement-based quantum key distribution (QKD). One pair of polarization spatial-mode hyperentanglement was distributed over 11 km multicore fiber (noisy channel). After purification, the fidelity of polarization entanglement arises from 0.771 to 0.887 and the effective key rate in entanglement-based QKD increases from 0 to 0.332. The values of Clauser-Horne-Shimony-Holt inequality of polarization entanglement arises from 1.829 to 2.128. Moreover, by using one pair of hyperentanglement and deterministic controlled-NOT gates, the total purification efficiency can be estimated as 6.6×10^{3} times than the experiment using two pairs of entangled states with spontaneous parametric down-conversion sources. Our results offer the potential to be implemented as part of a full quantum repeater and large-scale quantum network.

Pathways for Entanglement-Based Quantum Communication in the Face of High Noise.

Entanglement-based quantum communication offers an increased level of security in practical secret shared key distribution. One of the fundamental principles enabling this security-the fact that interfering with one photon will destroy entanglement and thus be detectable-is also the greatest obstacle. Random encounters of traveling photons, losses, and technical imperfections make noise an inevitable part of any quantum communication scheme, severely limiting distance, key rate, and environmental conditions in which quantum key distribution can be employed. Using photons entangled in their spatial degree of freedom, we show that the increased noise resistance of high-dimensional entanglement can indeed be harnessed for practical key distribution schemes. We perform quantum key distribution in eight entangled paths at various levels of environmental noise and show key rates that, even after error correction and privacy amplification, still exceed 1 bit per photon pair and furthermore certify a secure key at noise levels that would prohibit comparable qubit based schemes from working.

Effect of photobiomodulation therapy on mini-implant stability: a systematic review and meta-analysis.

The study aimed to assess trials investigating the effect of PBMT on mini-implant stability. Electronic searches of seven databases and manual search were conducted up to May 2020. Randomized controlled trials and controlled clinical trials evaluating the effect of PBMT on mini-implant stability were included. The risks of bias of individual studies were performed using ROB 2.0 and ROBINS-I-tool based on different study design. Meta-analysis was conducted to compare mini-implant stability exposed to PBMT with control ones at different time points after implantation. Among the 518 records initially identified, seven studies were included in this study. Six studies investigated low-level laser therapy (LLLT) and one study evaluated light-emitting diode (LED) therapy. Two studies were eligible for meta-analysis, which showed that LLLT significantly improved mini-implant stability 60 days after initial implantation (MD - 3.01, 95% CI range [- 4.68, - 1.35], p = 0.0004). High energy density of LLLT began to show beneficial effect on mini-implant stability as early as 3 days after implantation, while the significant effect of low energy density displayed later than 30 days after insertion. LED therapy could improve mini-implant stability after 2 months post-insertion. In conclusion, PBMT appears to be beneficial in ameliorating mini-implant stability. High energy density of LLLT might exert more rapid effect than low energy density. More high-quality clinical trials are needed to further demonstrate PBMT' effects on orthodontic mini-implants.

Long noncoding RNA expression profiles during the NEL-like 1 protein-induced osteogenic differentiation.

Long noncoding RNAs (lncRNAs) are important modulators of mesenchymal stem cells (MSCs) in cellular differentiation. However, the regulatory mechanisms of lncRNAs in NEL-like 1 (NELL-1)-induced osteogenic differentiation of human adipose-derived stem cells remain elusive. Expression profiles of lncRNAs and messenger RNAs during NELL-1-induced osteogenesis were obtained using high-throughput sequencing. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway analysis, and gene coexpression networks were performed. We identified 323 statistically differentially expressed lncRNAs during osteogenesis and NELL-1-induced osteogenesis, and three lncRNAs (ENST00000602964, ENST00000326734, and TCONS_00006792) were identified as core regulators. Hedgehog pathway markers, including IHH and GLI1, were downregulated, while the antagonists of this pathway (GLI3 and HHIP) were upregulated during NELL-1-induced osteogenesis. In this process, the antagonist of Wnt, SFRP1, was downregulated. According to the analysis, we speculated that lncRNAs played important roles in NELL-1-induced osteogenesis via the crosstalk between Hedgehog and Wnt pathways.

microRNA expression profiles and the potential competing endogenous RNA networks in NELL-1-induced human adipose-derived stem cell osteogenic differentiation.

Studies have indicated that Nel-like molecule-1 (NELL-1) was an osteoblast-specific cytokine and some specific microRNAs (miRNAs) could serve as competing endogenous RNA (ceRNA) to partake in osteogenic differentiation of human adipose-derived stem cells (hASCs). The aim of this study was to explore the potential functional mechanisms of recombinant human NELL-1 protein (rhNELL-1) during hASCs osteogenic differentiation. rhNELL-1 was added to osteogenic medium to activate osteogenic differentiation of hASCs. High-throughput RNA sequencing (RNA-Seq) was performed and validated by real-time quantitative polymerase chain reaction. Gene ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway analysis were performed to detect the functions of differentially expressed miRNAs and genes. Coding-noncoding gene co-expression network and ceRNA networks were constructed to predict the potential regulatory role of miRNAs. A total of 1010 differentially expressed miRNAs and 1762 differentially expressed messenger RNAs (mRNAs) were detected. miRNA-370-3p, bone morphogenetic protein 2 (BMP2), and parathyroid hormone like hormone (PTHLH) were differentially expressed during NELL-1-induced osteogenesis. Bioinformatic analyses demonstrated that these differentially expressed miRNAs and mRNAs enriched in Rap1 signaling pathway, PI3K-Akt signaling pathway, p53 signaling pathway, Glucagon signaling pathway, and hypoxia-inducible factor-1 signaling pathway, which were important pathways related to osteogenic differentiation. In addition, miRNA-370-3p and has-miR-485-5p were predicted to interact with circ0001543, circ0002405, and ENST00000570267 in ceRNA networks. Based on the gain or loss of functional experiments by transfection, the results showed that miR-370-3p was a key regulator in osteogenic differentiation by targeting BMP2 and disturbing the expression of PTHLH, and participated in NELL-1-stimulated osteogenesis. The present study provided the primary data and evidence for further exploration on the roles of miRNAs and ceRNAs during NELL-1-induced ossification of hASCs.

Experimental High-Dimensional Quantum Teleportation.

Quantum teleportation provides a way to transmit unknown quantum states from one location to another. In the quantum world, multilevel systems which enable high-dimensional systems are more prevalent. Therefore, to completely rebuild the quantum states of a single particle remotely, one needs to teleport multilevel (high-dimensional) states. Here, we demonstrate the teleportation of high-dimensional states in a three-dimensional six-photon system. We exploit the spatial mode of a single photon as the high-dimensional system, use two auxiliary entangled photons to realize a deterministic three-dimensional Bell state measurement. The fidelity of teleportation process matrix is F=0.596±0.037. Through this process matrix, we can prove that our teleportation is both nonclassical and genuine three dimensional. Our work paves the way to rebuild complex quantum systems remotely and to construct complex quantum networks.

Effect of clear aligners on oral health-related quality of life: A systematic review.

Clear aligners have been frequently applied in orthodontic clinic practice. However, its effect on oral health-related quality of life (OHRQoL) compared with fixed appliance treatment (FAT) remains inconclusive. This systematic review aimed to compare the impacts of clear aligner treatment (CAT) with FAT on patients' OHRQoL. Electronic searches of databases (PubMed, Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, Embase, Medline, two Chinese databases and six grey literature databases) were conducted up to July 2019. Randomized controlled trials, controlled clinical trials, cohort studies and cross-sectional studies comparing the impact of CAT and FAT on OHRQoL with validated instruments were included. Extraction of data and assessment of the risk of bias were conducted using ROBINS-I-tool, Newcastle-Ottawa Scale and ROB 2.0 based on study design. Of the 1112 records initially identified, 2 studies were included in this review. One study evaluated OHRQoL at the last debonding appointment, while the other made evaluation at the early stage of treatment. In the aspect of functional dimensions, both studies reported less eating disturbance in CAT patients than FAT ones. Based on currently limited information, the effect of CAT on the overall OHRQoL compared to FTA was still inconclusive. In individual dimensions, however, weak evidence supported that CAT might cause less eating disturbance than FAT. More high-quality clinical trials using validated OHRQoL instruments are needed to draw more reliable conclusions in the effect of CAT and FAT on OHRQoL.

[Diagnosis and Treatment of 43 Patients with IgG4-related Disease].

OBJECTIVE: To summarize the clinicopathological characteristics, diagnosis and treatment of IgG4-related disease (IgG4-RD). METHODS: The clinical data of 43 cases with IgG4-RD diagnosed from January 2013 to December 2017 were retrospectively analyzed. The clinical data of the patients including clinical characteristics, accessory examinations, diagnosis, and treatment were collected. RESULTS: Among the 43 patients with IgG4-RD, the ratio of male to female was 3∶1, the mean age was (51.3±15.9) years. Eleven patients had gastrointestinal symptoms, including 5 cases of IgG4-related cholangitis with the feature of dilation of the biliary system and narrowing of the lumen in the abdominal enhanced CT scans, and 6 cases of IgG4-related autoimmune pancreatitis with the feature of pancreatic enlargement or soft tissue density shadow in the abdominal enhanced CT scans. There were 10 cases (23.3%) with periorbital involvement, with the feature of intraorbital soft tissue nodule in the CT scan. Besides, 9 cases (20.9%) had lymphadenopathy, 6 cases (14.0%) had fever. The results of autoimmune antibody tests showed that 14 of 42 patients had increased antinuclear antibody (ANA). Among 40 patients who underwent immunoglobulin tests, 25 cases had elevated IgG, 12 cases had increased IgA, and 29 cases had increased IgE. Coombs test were performed for 6 cases and 4 patients were positive. Serum immunoglobulin G4 subtypes showed that the IgG4 levels of 35 patients were higher than 1 350 mg/L. The immunohistochemistry showed that IgG4 (+) cells (3->500/HPF) were infiltrated, with the CD20 (+), CD3ε (+) or CD138 (+). Among the 43 patients, 5 patients underwent operations due to misdiagnosis. All patients were treated with steroid and immunosuppressive agents after diagnosis, and their clinical symptoms were improved. CONCLUSION: The clinical symptoms of IgG4-RD are various, involving multiple organs. Therefore, the standardized diagnosis and treatment of IgG4-RD should be strengthened.

The roles of circRFWD2 and circINO80 during NELL-1-induced osteogenesis.

Bone defects caused heavy social and economic burdens worldwide. Nel-like molecule, type 1 (NELL-1) could enhance the osteogenesis and the repairment of bone defects, while the specific mechanism remains to be elucidated. Circular RNAs (circRNAs) have been found to play critical roles in the tissue development and serve as biomarkers for various diseases. However, it remains unclear that the expression patterns of circRNAs and the roles of them played in recombinant NELL-1-induced osteogenesis of human adipose-derived stem cells (hASCs). In this study, we performed RNA-sequencing to investigate the expression profiles of circRNAs in recombinant NELL-1-induced osteogenic differentiation and identified two key circRNAs, namely circRFWD2 and circINO80. These two circRNAs were confirmed to be up-regulated during recombinant NELL-1-induced osteogenesis, and knockdown of them affected the positive effect of NELL-1 on osteogenesis. CircRFWD2 and circINO80 could interact with hsa-miR-6817-5p, which could inhibit the osteogenesis. Silencing hsa-miR-6817-5p could partially reverse the negative effect of si-circRFWD2 and si-circINO80 on the osteogenesis. Therefore, circRFWD2 and circINO80 could regulate the expression of hsa-miR-6817-5p and influence the recombinant NELL-1-induced osteogenic differentiation of hASCs. It opens a new window to better understanding the effects of NELL-1 on the osteogenic differentiation of hASCs and provides potential molecular targets and novel methods for bone regeneration efficiently and safely.