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Graves' orbitopathy (GO) is a disfiguring and sight-threatening autoimmune disease. Previous studies have shown the infiltration of macrophages in GO orbital connective tissues. However, the immunophenotypes of macrophages and their modulatory effects on orbital fibroblasts (OF) have not been examined so far. In this study, we sought to determine the pathophysiology of macrophages in GO.In this case-control study, orbital connective tissues collected from 40 GO patients and 20 healthy controls were immunohistochemically stained for cytokines and macrophage cell surface antigens. The polarization of orbital-infiltrating macrophages was investigated by flow cytometry and immunofluorescence. Effects of interleukin (IL)-6 combined with soluble IL-6 receptor (sIL-6R) on the proliferation, differentiation, and inflammation of different OF subsets were examined by CCK-8, Western blotting, and Luminex assays, respectively. The antigen-presenting abilities of different OF subsets under IL-6/sIL-6R signaling were studied by proteomics. Finally, the differentiation of CD8+ IL-17A-producing T cells by sIL-6R was tested.GO orbital connective tissues displayed increased IL-6, sIL-6R, STAT3, and IL-17A levels. CD86+ M1-like macrophages were predominant in active GO patients whilst stable GO patients tended to have more CD163+ M2-like macrophages. The expression of IL-6 was higher in M1-like macrophages and the expression of transforming growth factor-β was higher in M2-like macrophages both in GO orbital connective tissues in situ in vivo and in cell culture system in vitro. The IL-6/sIL-6R stimulation promoted the fibrosis of both CD34+ and CD34- OFs. Monocyte chemoattractant protein-1 expression was also induced by IL-6/sIL-6R stimulation in both OF subsets. IL-6/sIL-6R stimulation enhanced antigen processing of CD34+ OFs via up-regulating the intact major histocompatibility complex I and antigen transporters. However, the protein expressions of thyroid-stimulating hormone receptor and insulin-like growth factor 1 receptor could not be directly increased by IL-6/sIL-6R stimulation in CD34+ OFs. Furthermore, sIL-6R was conducive to the differentiation of CD8+ IL-17A-producing T cells.Our study demonstrated the immunophenotypes of orbital-infiltrating macrophages that may activate OFs depending on the IL-6/sIL-6R signaling in GO. Our preclinical findings implicate, at least in part, the molecular rationale for blocking sIL-6R as a promising therapeutic agent for GO.

Purpose The purpose of this article is to investigate the characteristics of Th1-cell and Th17-cell lineages for very severe Graves orbitopathy (GO) development. Methods Flow cytometry was performed with blood samples from GO and Graves disease (GD) patients and healthy controls, to explore effector T-cell phenotypes. Lipidomics was conducted with serum from very severe GO patients before and after glucocorticoid (GC) therapy. Immunohistochemistry and Western blotting were used to examine orbital-infiltrating Th17 cells or in vitro models of Th17 polarization. Results In GD, Th1 cells predominated in peripheral effector T-cell subsets, whereas in GO, Th17-cell lineage predominated. In moderate-to-severe GO, Th17.1 cells expressed retinoic acid receptor-related orphan receptor-γt (RORγt) independently and produced interleukin-17A (IL-17A), whereas in very severe GO, Th17.1 cells co-expressed RORγt and Tbet and produced interferon-γ (IFN-γ). Increased IFN-γ–producing Th17.1 cells positively correlated with GO activity and were associated with the development of very severe GO. Additionally, GC therapy inhibited both Th1-cell and Th17-cell lineages and modulated a lipid panel consisting of 79 serum metabolites. However, in GC-resistant, very severe GO, IFN-γ–producing Th17.1 cells remained at a high level, correlating with increased serum triglycerides. Further, retro-orbital tissues from GC-resistant, very severe GO were shown to be infiltrated by CXCR3+ Th17 cells expressing Tbet and STAT4 and rich in triglycerides that promoted Th1 phenotype in Th17 cells in vitro. Conclusions Our findings address the importance of Th17.1 cells in GO pathogenesis, possibly promoting our understanding of the association between Th17-cell plasticity and disease severity of GO.

To evaluate the age-related difference in EOMs and its relation to clinical manifestations by computed tomography (CT) measurement of EOMs. The medical records and CT image review of 40 patients (80 orbits) with moderate-to-severe Graves’ orbitopathy were performed. The patients were divided into two age groups, group 1 (≤ 40 years) and group 2 (> 40 years). CT scans of 30 gender- and age-matched normal controls were also obtained. The maximal cross-sectional area (MCA) and its position (pMCA) of each EOM were measured. Group 1 presented with more severe proptosis (p

Context Unique features of local immunity in thyroid-associated ophthalmopathy (TAO) may affect disease progression. Objective To investigate the association between the orbital immune microenvironment and TAO development. Design/setting/participants TAO and control orbital connective tissues were collected. Main outcome measures Single-cell sequencing examined orbital lymphocytic infiltrates. Multicolor flow cytometry explored the phenotypes of different cell subsets and in vitro models for cell functional studies. Coculture experiment and western blotting assay were used to determine underlying mechanism of the enhanced T helper 17 (Th17) cell pathway. Results The TAO orbital microenvironment was composed of natural killer cells, dendritic cells, macrophages, T cells, plasma cells, and CD34+ orbital fibroblasts, but few B cells. Increases in CD3+CD8- IL-17A-producing and RAR-related orphan receptor (ROR)γt-expressing T cells and in CD3+CD8- IL-13-producing and GATA3-expressing T cells suggested Th17 and Th2 cell responses in TAO orbits. Increased interferon-γ (IFN-γ)-producing and RORγt+Tbet+ T cells indicated a Th1-like phenotype of orbital-infiltrating Th17 cells. Higher IL-23R and IL-1R expression and lower IL-21R expression were also observed on Th17 cells in TAO orbits. Multivariate analyses revealed that the Th17 pathway [IL-17A (P = 0.001), IFN-γ (P = 0.009), RORγt (P = 0.003), IL-23R (P = 0.033), IL-21R (P = 0.019)], and Th2 pathway [IL-13 (P = 0.015), GATA3 (P = 0.012)] were associated with TAO. IL-17A, IL-23R, and IL-1R correlated with clinical activity score and visual acuity. CD34+ orbital fibroblasts exhibited distinct cell surface marker expression and promoted IL-23R and IL-1R expression on T cells to facilitate the Th17-cell phenotype through prostaglandin E2-EP2/EP4-cAMP signaling. Conclusion Our study addresses the importance of retroorbital immunity and suggests possible means of disrupting TAO pathogenesis.

Geological hazards such as destructive earthquake severely limit the speed and the scale of urbanization at urban scale. However, whether the historical earthquake exert persistent or temporary effects on the urbanization process at county scale also remain intertwined. The 2008 Wenchuan earthquake was an unparalleled natural disaster in China history, and the Dujiangyan county is one of the ten worst-hit counties. Taking the Dujiangyan county as a case study, we established an indexing systems for urbanization at a county scale. The urbanization level at the county scale was gauged from three dimensions including population, economy and space. The coordinate assessment indicated that the urbanization process at the scale of county had obvious phase characteristics before and after the natural disasters. The suitable post-disaster policies and measures could strengthen the coupling coordination degree among the population, economy and space at the county scale. Triangle analysis indicated the urbanization model of the Dujiangyan county was basically a shift from space-dominated to population-dominated before and after the earthquake. It's indispensable to improve the quality of geological environment to minimize the threats and losses rendered by earthquake and facilitate sustainable urbanization process at county scale.

Objective To evaluate magnetic resonance imaging parameters, T2 signal intensity ratios (SIRs), and normalized apparent diffusion coefficients (n-ADC) of the extraocular muscles (EOMs) in the identification of different stages of Graves’ ophthalmopathy (GO) and to find out the correlation of T2-SIRs and n-ADC values with disease changes after anti-inflammatory treatment. Methods Altogether, 43 patients (86 orbits) were enrolled and classified into “active” or “inactive” stages by clinical activity score (CAS). Twenty-three (53.5%) patients received anti-inflammatory treatment and underwent a follow-up evaluation. Fifteen age- and gender-matched control participants (30 orbits) were included. T2-SIRs and n-ADC values of EOMs were calculated among GO and healthy controls and were correlated with CAS. Changes in these parameters were also evaluated before and after anti-inflammatory treatment. Results Mean T2-SIRs and n-ADC values were both significantly higher in GO patients than in controls and higher in active GO than in inactive GO. In the inactive stage, n-ADC values of inferior rectus muscles were still higher than those in healthy controls. Both T2-SIRs and n-ADC values decreased after intravenous steroid pulse therapy. The cutoff value of pretreatment n-ADC was 1.780 to detect stages with specificity of 93.7% and sensitivity of 48.3% (P = .035). Conclusion T2-SIRs and n-ADC values are valuable magnetic resonance imaging indicators of the inflammatory activity in GO by detecting involvement of EOMs. They are also ideal tools to monitor the efficacy of anti-inflammatory treatment in patients with active stage GO. n-ADC values, when combined with CAS, can be promising predictive factors in the detection of stages of diseases.

Inflammation and coagulation are two important processes implicated in venous thromboembolism (VTE). 15-epi-lipoxin A4 (15-epi-LXA4) is the epimer of LXA4, a small lipid molecule, is known to play a key role in the resolution of inflammation. This study aimed to demonstrate whether 15-epi-LXA4 could suppress the inflammatory factor tumor necrosis factor-alpha (TNF-α)-induced upregulation of tissue factor (TF), an important regulator of the blood coagulation cascade, and evaluated the possible underlying mechanisms. We found that 15-epi-LXA4 not only reduced the up-regulation of mRNA and antigens, but also lowered the activity of TF (elevated by TNF-α) in primary culture of human umbilical vein endothelial cells (pc-HUVECs). In addition, 15-epi-LXA4 suppressed the activation of the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway, induced by TNF-α, in pc-HUVECs. 15-epi-LXA4 also inhibited the binding of NF-κB on the TF promoter, which is otherwise enhanced by TNF-α. The role of 15-epi-LXA4 in regulating TNF-α-induced effects was enhanced by the PI3K inhibitor and prevented by the PI3K activator. In conclusion, 15-epi-LXA4 lowered the TNF-α-induced high TF expression and activity by suppressing PI3K/AKT signaling activation, thereby reducing the binding capacity of NF-κB on the TF promoter in pc-HUVECs.

Inflammation and coagulation are two important processes implicated in venous thromboembolism (VTE). 15-epi-lipoxin A

BACKGROUND Eyelid retraction is the most common and often the first sign of thyroid eye disease (TED). Upper-eyelid retraction causes both functional and cosmetic problems. In order to correct the position of the upper eyelid, surgery is required. Many procedures have demonstrated good outcomes in mild and moderate cases; however, unpredictable results have been obtained in severe cases. Dryden introduced an upper-eyelid-lengthening procedure, which used scleral grafts, but outcomes were unsatisfactory. A new technique is introduced in this study as a reasonable alternative for TED-related severe upper-eyelid retraction correction. MATERIAL AND METHODS An innovative technique for levator lengthening using bovine acellular dermal matrix as a spacer graft is introduced for severe upper-eyelid retraction secondary to TED. Additionally, 2 modifications were introduced: the fibrous cords scattered on the surface of the levator aponeurosis were excised and the orbital fat pad anterior to the aponeurosis was dissected and sutured into the skin closure in a "skin-tarsus-fat-skin" fashion. RESULTS The modified levator-lengthening surgery was performed on 32 eyelids in 26 patients consisting of 21 women and 5 men (mean age, 37.8 years; age range, 19-67 years). After corrective surgery, the average upper margin reflex distance was lowered from 7.7±0.85 mm to 3.3±0.43 mm. Eighteen cases (69%) had perfect results, while 6 cases (23%) had acceptable results. CONCLUSIONS A modified levator-lengthening procedure using bovine acellular dermal matrix as a spacer graft ameliorated both the symptoms and signs of severe upper-eyelid retraction secondary to TED. This procedure is a reasonable alternative for correction of TED-related severe upper-eyelid retraction.

The aim of this study was to compare the surgical outcomes of deep lateral orbital decompression using the rim-sparing technique versus the rim-removal technique in Graves’ orbitopathy (GO). A retrospective cohort study of 75 orbits in 50 patients with GO was performed. Proptosis, best corrected visual acuity (BCVA), intraocular pressure (IOP), upper and lower lid margin to reflex distances (MRD-1 and MRD-2, respectively), diplopia, ocular restriction, and GO quality of life (GO-QOL) questionnaire results were analyzed pre- and postoperatively. The average proptosis reduction ranged from 3.5 mm to 6.7 mm with the rim-sparing technique and from 3.6 mm to 6.7 mm with the rim-removal technique ( P > 0.05). All orbits with dysthyroid optic neuropathy in the rim-sparing group and 87.5% of such orbits in the rim-removal group showed improved BCVA ( P = 0.321). Reductions in IOP, MRD-1, and MRD-2 were observed with both techniques. Patients in the rim-sparing group had greater improvements in GO-QOL appearance score ( P = 0.043). In conclusion, rim-sparing orbital decompression provides efficacious outcomes with greater improvements in patient quality of life than the rim-removal technique. The rim-sparing technique should be considered as a preferable option because it preserves the integrity of the lateral vertical maxillary buttress and bony protection for the orbital contents.

Background Thyroid eye disease (TED) is a debilitating autoimmune orbital disease that is often a result of Graves’ disease. Dysthyroid optic neuropathy (DON) is a rare but sight-threatening manifestation of TED with therapeutic challenges that can potentially lead to visual loss. Case presentation A 74-year-old man experienced active TED with extremely severe redness and swelling of the conjunctiva, loss of visual acuity and exacerbation of disfiguring proptosis. Computed tomography revealed the involvement of extraocular muscles resulting in optic nerve compression. He was in poor general condition and was intolerant to steroids. To achieve the optimal operating conditions for orbital decompression surgery, the patient was initially treated with orbital radiotherapy. The patient responded well, with improvements in clinical activity score and visual acuity. Conclusion This case demonstrates a rare and severe case of DON with therapeutic challenges. To date, no cases has been reported of a patient with such severe and unusual ocular manifestations. Early awareness of the occurrence of optic nerve compression and prompt treatment are important to prevent irreversible outcomes. Orbital radiotherapy should be considered as a useful surgery-delaying alternative for DON, especially in patients who have contraindications to steroids.

Background Intravenous glucocorticoids (ivGC) have been recommended as a first-line treatment of moderate-to-severe and active thyroid-associated ophthalmopathy (TAO). However, not all patients are responsive to ivGC. The identification of potential factors used to predict their efficacy and the selection of suitable patients have both been lacking. Methods It was a single center retrospective study. Potential factors related to the effects of ivGC were analyzed using logistic regression in 90 consecutive patients with moderate-to-severe and active TAO, who received 4.5 g ivGC therapy. Response was defined as the achievement of at least three points of the overall response. Results Fifty-two (57.8%) patients showed a positive response to ivGC therapy. Significant correlations were observed between the effects of ivGC and pretreatment clinical activity score (CAS), duration of eye symptoms, and restoration of euthyroidism. The two latter factors were both independent. The duration of eye symptoms was negatively correlated with the effects of ivGC, with an odds ratio (OR) of 0.984 (p = 0.012). Restoration of euthyroidism (OR = 3.282, p = 0.039) and pretreatment CAS (OR = 1.653, p

Context T helper (Th)17 cells are correlated with many human autoimmune disorders, including Graves disease, and may play key roles in the pathogenesis of Graves orbitopathy (GO). Objective To study the phenotype of Th17 cells in patients with GO and healthy subjects, investigate the fibrosis and adipogenesis in orbital fibroblasts (OFs) modulated by interleukin (IL)-17A, and determine the interaction between Th17 cells and OFs. Design/Setting/Participants Blood samples and orbital tissues from GO patients and healthy controls were collected. Main Outcome Measures We conducted multicolor flow cytometry, immunohistochemical and immunofluorescent stainings, Western blotting, a PathScan intracellular signaling assay, Luminex and enzyme-linked immunosorbent assays, and protein mass spectrum. Results Interferon-γ– and IL-22–expressing Th17 cells are increased in GO patients, which are positively related to clinical activity score. Costimulatory molecules are highly expressed in GO orbits and most GO OFs are CD90+. IL-17A promotes TGF-β–induced fibrosis in CD90+ OFs but impedes 15-deoxy-Δ12,14-prostaglandin J2–induced adipogenesis in CD90− OFs. Th17 cells promote proinflammatory cytokine secretion in both CD90+ and CD90− OFs. Meanwhile, both CD90+ and CD90− OFs contribute to Th17 cell differentiation through prostaglandin E2 production, which can be attenuated by indomethacin. Furthermore, Th17 cells upregulate costimulatory molecule expression on OFs. Conclusion Our findings unravel the pathogenicity of IL-17A in the initiation and progression of GO. In-depth interpretation of the molecular basis of OFs delineated by CD90 and Th17–OF interaction will help to afford a novel approach to better therapeutic strategies for GO.

Exploring visible light responsive media remains a challenge for solar energy photocatalysis applications. We report the Ni3S2-reduced graphene oxide (NG) hybrid composites with sheet-on-sheet structures synthesized by a facile microwave-assisted method. Their morphology, structure and photocatalytic activity in the reduction of Cr(VI) were characterized by scanning electron microscopy, X-ray diffraction, UV-Vis absorption spectroscopy, and electrochemical impedance spectra, respectively. The results show that NG hybrid composites show excellent visible light photocatalytic activity in the reduction of Cr(VI) compared to pure Ni3S2. The Cr(VI) reduction rate of higher than 90% has been achieved with 1wt.% reduced graphene oxide under visible light irradiation at 180min. Improvement is attributed to its efficient charge separation and more active sites due to the integrative effect and good interfacial contact between Ni3S2 and reduced graphene oxide.

Purpose This present study aims to investigate the phenotype of IL-17A-producing T cells in thyroid-associated ophthalmopathy (TAO) and the role of IL-17A on RANTES and IL-16 expression in orbital fibroblasts (OFs) from TAO patients. Methods Blood samples were obtained from TAO patients and healthy controls and were subjected to ELISA and flow cytometry analysis. Primary human OFs cultured from surgical wastes were stimulated with IL-17A in the presence or absence of CD40L and were examined by qRT-PCR, ELISA, Western blotting, and apoptosis assays. Results We reported upregulated IL-17A, IFN-γ, RANTES, and IL-16 serum levels and increased frequency of IL-17A- and IFN-γ-producing T cells in peripheral blood mononuclear cells from patients with TAO compared with healthy controls. In addition, TAO orbital tissues were rich in T lymphocytes, expressing more IL-17A, IFN-γ, RANTES, and IL-16. Moreover, IL-17A could enhance the expression of RANTES, but not IL-16, in cultured primary OFs in cooperation with CD40L. We further validated that MAPK signaling was largely responsible for RANTES production in IL-17A-treated OFs. Finally, we demonstrated that IL-17A could not promote apparent apoptosis in OFs from TAO patients and healthy controls. Conclusions Our results indicate the potent effect of IL-17A-induced RANTES expression on OFs and elaborate a possible mechanism in understanding Th17 cells in the pathology of TAO and its potential as a target to immunotherapy of TAO and other autoimmune disorders.

Rationale: The differential diagnosis of conditions manifesting as bone and joint pain is complex. Although many individuals with acute leukemia experience bone pain, lumbosacral pain as an early feature of acute lymphoblastic leukemia (ALL) is rare. Patient concerns: Here we report a case of an adult who presented with a 7-month history of persistent lumbosacral pain which had become more severe during the previous month. Diagnoses: Prior to referral, his full blood count revealed no abnormalities, and a computerized tomography scan revealed mild bone hyperplasia of his lumbar vertebrae, with disc herniations of L3–S1. His blood biochemistry and urinary test results had been normal. After referral to our clinic, tests of the morphology, immunology, cytogenetics, and molecular biology of his bone marrow led to a diagnosis of MLL-AF4 fusion positive B-cell ALL. Interventions: Prior to his referral, he had been treated with painkillers by local doctors. The painkillers initially provided pain relief, but their effect wore off over time. After diagnosis, he was started on an adult ALL chemotherapy protocol. Outcomes: His symptoms resolved within a week of starting chemotherapy. At his most recent assessment, 10 months after diagnosis, he was on maintenance chemotherapy and in remission. Lessons: This case illustrates that prolonged lumbosacral pain may be a symptom of a life-threatening condition, rather than only attributable to chronic inflammation or disk herniations. Therefore, clinicians need to pay attention to subtle differences in the clinical presentation of patients with lumbosacral pain.

Context: The development of thyroid-associated ophthalmopathy (TAO) is associated with self-immune dysfunction. Recent findings in TAO and Graves' disease indicate that IL-17A may also be involved in the autoimmunity of TAO. Objective: We sought to investigate the pathogenic function of IL-17A-producing T cells in TAO. Design/Setting/Participants: Blood samples and orbital fibroblasts (OFs) were collected from TAO patients and healthy subjects. Main Outcome Measures: Flow cytometry, real-time PCR, cytokine-specific ELISA, and Western blotting were performed. Results: Here, we showed a significantly higher proportion of IL-17A-producing T cells in TAO patients and the recruitment of both CD4+ and CD8+ T cells in TAO orbits. TAO orbital tissues expressed more IL-17A receptor, IL-17A, and its related cytokines, with severe fibrotic change compared with normal controls. Furthermore, we validated that IL-17A could enhance the proinflammatory function of OFs and stimulate the production of extracellular matrix proteins in OFs but not eyelid fibroblasts. The mechanisms involved in this enhancement mainly relied on MAPK activation. Finally, we observed that the deubiquitinase inhibitor vialinin A could down-regulate retinoic acid receptor-related orphan receptor-γt expression and decrease IL-17A level in TAO patients. Conclusion: Our observations illustrate the potential pathogenic role of IL-17A-producing T cells in the inflammatory response and fibrosis of TAO. The effect of vialinin A on the reduction of retinoic acid receptor-related orphan receptor-γt level implicates its potential role as a novel therapeutic agent for TAO and other autoimmune disorders in the future.

Purpose Recent reports suggest that Th17 immunity and bone marrow-derived CD34+ fibrocytes contribute to the pathogenesis of Graves' orbitopathy (GO). This study investigated interactions between Th17 cells and fibrocytes in GO inflammation in Chinese subjects. Methods Th17 cells and fibrocytes were derived from blood samples from Chinese GO patients and healthy controls. Proportions and phenotypes of Th17 cells, regulatory T cells (Tregs), and fibrocytes were examined by flow cytometry. Exogenous IL-17A was used to study inflammatory activity of fibrocytes from GO patients and control subjects. Coculture, quantitative RT-PCR, Luminex, and transwell assays were performed to investigate the relationship between Th17 cells and fibrocytes. Results CC-chemokine receptor 6 (CCR6+) Th17 cells were increased in both active (P < 0.001) and inactive (P < 0.05) GO patients, compared with healthy controls. There was a positive correlation between number of CCR6+ Th17 cells and GO clinical activity score (P < 0.0001, r = 0.8176). Further, CD34+ fibrocytes were increased in GO patients, with increased expression of IL-17RA (P < 0.05), CD80 (P < 0.05), and CD86 (P < 0.05). A decreased population of effector Treg cells (P < 0.01) and increased CTLA-4 expression on naive Treg cells (P < 0.05) were observed in GO patients. IL-17A stimulated cytokine production in fibrocytes; GO fibrocytes exhibited more robust production than normal fibrocytes. Autologous Th17 cells promoted inflammatory and antigen-presenting functions of GO fibrocytes; conversely, fibrocytes enhanced Th17 cell-function and recruited Th17 cells in a macrophage inflammatory protein 3 (MIP-3)/CCR6-dependent manner. Conclusions The crosstalk between CCR6+ Th17 cells and fibrocytes plays a role in the pathogenesis of GO. Suppressing these interactions may be a candidate molecular target for therapeutic approaches of GO.

Recently, several techniques have been proposed to preserve the user location privacy in road networks. To protect the location privacy of users, many of the existing techniques adopt cloaking which blurs the actual location into a set of segments. But these techniques do not take the weight of the segments into account in the situation of road networks. In this paper, we propose a new attack model that an adversary can infer the true location of the requester according to the weight distribution with a certain probability. And we also design an approach to solve this problem, which can guarantee better distribution of the weights in the cloaked set. The experiment result shows the effectiveness and feasibility of our algorithm.

The query privacy issue in location-based services (LBS) has recently received considerable attention. To protect the query privacy of users, current state-of-the-art techniques adopt cloaking which cloaks the sender's location to k-anonymized spatial region (ASR), such that an attack based on the sender's location cannot identify the query source with probability larger than 1/k, among other k-1 users. However, these techniques do not consider that these k-1 additional mobile users with different privacy requirements may send request at the same time. In this paper, we propose a new attack model that an adversary who observes all the ASRs at one time can identify the query source with probability larger than 1/k based on prior knowledge of the locations of all users. And we propose our two algorithms, namely, Basic and Adaptive Algorithms, which strengthen the privacy guarantee to defend such inference attack while still support personalized user privacy requirements. We verify the effectiveness of the proposed algorithms by experiments on location data which synthetically generated on real road maps.

When mobile users search points of interest in location based services, they should always provide their accurate locations, which may leak location privacy of themselves. A typical approach to protect user location privacy is to generate a cloaked region (CR) that encloses the user position. However, if locations are continuously reported, an attacker can correlate CRs from multiple timestamps to accurately pinpoint the user position within a CR. In this paper, we present a novel approach, called Extended Guess-Answer, to protect against velocity-based linkage attacks in location based services. Through the interaction between the user and the server, a cloaked region that contains user current location can be generated. The experimental results show that our approach is effective and feasible.

when mobile users search points of interest from location based service, they always should provide their accurate locations, which may leak users' location privacy. To protect users' location privacy, some two-tie approaches have been imposed. However, existing approaches are either hard to implement or may lead to high communication cost. In this paper, we present a novel approach, called Guess-Answer. Through the interaction between the user and the server, a cloaked region, which satisfies the user's personal privacy requirement, can be generated. The experimental results show that our approaches are scalable and robust.

When mobile users retrieve interested location information through location based service (LBS), they should always provide their accurate location, which may leak their location privacy. In order to prevent privacy leakage when service provider is not reliable, some solutions based on two ties architecture are proposed. However, these solutions are either hard to implement or may lead to huge communication cost. In this paper, we present a novel technique, called Guess-Answer. Through the interaction between user and server, the location information within a region that satisfies the minimum privacy requirement of the user would be delivered. Through proper analysis and experimental study, we demonstrate that Guess-Answer is an efficient and effective way to achieve personalized privacy.