Altered expression of microRNAs targeting Dkk-1 in peripheral blood mononuclear cells of patients with ankylosing spondylitis.

INTRODUCTION: Ankylosing spondylitis (AS) is a chronic inflammatory disease characterised by new bone formation, and Dickkopf homologue 1 (Dkk-1) may contribute to the ankylosis of the sacroiliac joint as a main regulator of the Wingless (Wnt) pathway. Increasing evidence shows that microRNAs targeting Dkk-1 might play a critical role in the pathogenesis of rheumatic diseases. We aim to investigate alterations in expression of miRNAs targeting Dkk-1 in AS patients in this study. MATERIAL AND METHODS: The peripheral blood mononuclear cells (PBMCs) of 20 AS patients and 20 normal controls were collected in our study. Three miRNAs targeting DKK1 including miR-29a, miR-335, and miR-363 were selected and quantitative real-time PCR was used to identify the expression of the three miRNAs in these samples. Correlation analysis was conducted between altered miRNA expression and erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Function Index (BASFI), and mSASSS (modified Stoke Ankylosing Spondylitis Spinal Score). RESULTS: The expression of miR-29a was significantly higher in AS patients than in healthy controls (p < 0.01), while no significance was observed in the expression of miR-335 and miR-363 between AS patients and healthy controls (p > 0.05). No correlation was observed between miR-29a and ESR, CRP, BASDAI, and BASFI (p > 0.05). The elevated miR-29a expression was correlated with disease duration and mSASSS (p < 0.05). CONCLUSIONS: MiR-29a might be a useful marker in AS new bone formation and contributes to the regulation of Dkk-1 in Wnt signalling.

MiR-29a and Messenger RNA Expression of Bone Turnover Markers in Canonical Wnt Pathway in Patients with Ankylosing Spondylitis.

BACKGROUND: Recent studies showed that the canonical Wnt pathway and miR-29a play important roles in the pathogenesis of bone formation. We studied the levels of miR-29a and messenger RNA (mRNA) of bone turnover markers in the canonical Wnt pathway in ankylosing spondylitis (AS). METHODS: The levels of miR-29a and mRNA of bone turnover markers in canonical Wnt pathway from peripheral blood mononuclear cells were determined by real-time quantitative polymerase chain reaction in 38 patients with AS and 32 healthy controls. Correlation analysis was conducted between the levels of miR-29a and mRNA and clinical measurements using Spearman's correlation test. RESULTS: Compared to healthy controls, the levels of miR-29a, Dickkopf (DKK)-1, ß-catenin and Runx2 mRNA were significantly higher in AS patients (p < 0.05). In contrast, the levels of Gsk-3ß mRNA was significantly lower in AS patients than that in healthy controls (p < 0.05). Gsk-3ß mRNA was positively correlated with ß-catenin mRNA expression (p < 0.05) and no other correlation was observed between any other markers (p > 0.05). Only DKK-1 mRNA expression was negatively correlated with disease course (p < 0.05) and no other correlation was observed between markers and clinical measurements (p > 0.05). CONCLUSIONS: The osteoblastic marker miR-29a and downstream mRNA of canonical Wnt signaling was upregulated in AS, suggesting their possible role in new bone formation in AS.

Elevated miR-29a expression is not correlated with disease activity index in PBMCs of patients with ankylosing spondylitis.

OBJECTIVES: Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by new bone formation. Recent evidence suggests that new bone formation in AS may be due to upregulation of Wnt signaling in the osteoblastic pathway secondary to low serum Dickkopf homolog 1 (Dkk-1) levels. And miR-29a orchestrates osteoblast differentiation through direct targeting and negative regulation of Dkk-1. METHODS: We initially validated the expression levels of miR-29a in the peripheral blood mononuclear cells (PBMCs) of AS patients (n = 30), rheumatoid arthritis (RA) patients (n = 30) and healthy controls (n = 30) using real-time quantitative reverse transcription PCR (qRT-PCR). Correlation analysis was assessed between miR-29a level in PBMCs of AS patients and disease activity indexes, including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis function index (BASFI) and modified Stoke ankylosing spondylitis spinal score (mSASSS). RESULTS: Significantly higher expression of miR-29a was observed in PBMCs of AS patients (Ct 9.18 ± 1.96) compared with that in RA patients (10.97 ± 0.70, p < 0.001) and healthy controls (Ct 11.45 ± 1.23, p < 0.001). There was no significant difference between RA patients and healthy controls in miR-29a expression (p > 0.05). Elevated miR-29a expression is not correlated with disease activity index (p > 0.05). A weak correlation was found between elevated miR-29a expression and mSASSS (r = -0.393, p = 0.032). CONCLUSIONS: We report for the first time elevated miR-29a expression in PBMCs of patients with ankylosing spondylitis, and miR-29a might be used as a useful diagnostic marker in new bone formation but cannot reflect disease activity.

Elevated miR-29a expression is not correlated with disease activity index in PBMCs of patients with ankylosing spondylitis.

OBJECTIVES: Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by new bone formation. Recent evidence suggests that new bone formation in AS may be due to upregulation of Wnt signaling in the osteoblastic pathway secondary to low serum Dickkopf homolog 1 (Dkk-1) levels. And miR-29a orchestrates osteoblast differentiation through direct targeting and negative regulation of Dkk-1. METHODS: We initially validated the expression levels of miR-29a in the peripheral blood mononuclear cells (PBMCs) of AS patients (n = 30), rheumatoid arthritis (RA) patients (n = 30) and healthy controls (n = 30) using real-time quantitative reverse transcription PCR (qRT-PCR). Correlation analysis was assessed between miR-29a level in PBMCs of AS patients and disease activity indexes, including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis function index (BASFI) and modified Stoke ankylosing spondylitis spinal score (mSASSS). RESULTS: Significantly higher expression of miR-29a was observed in PBMCs of AS patients (Ct 9.18 ± 1.96) compared with that in RA patients (10.97 ± 0.70, p < 0.001) and healthy controls (Ct 11.45 ± 1.23, p < 0.001). There was no significant difference between RA patients and healthy controls in miR-29a expression (p > 0.05). Elevated miR-29a expression is not correlated with disease activity index (p > 0.05). A weak correlation was found between elevated miR-29a expression and mSASSS (r = -0.393, p = 0.032). CONCLUSIONS: We report for the first time elevated miR-29a expression in PBMCs of patients with ankylosing spondylitis, and miR-29a might be used as a useful diagnostic marker in new bone formation but cannot reflect disease activity.

[The expression of MMP-2 and MMP-9 in adenoid cystic carcinoma of lacrimal gland].

OBJECTIVE: To investigate the expression of matrix metal proteinase (MMP)-2 and MMP-9 in adenoid cystic carcinoma of lacrimal gland as well as their relation with biological behaviour of adenoid cystic carcinoma. METHODS: Experimental study. The research objects were 60 cases of adenoid cystic carcinoma of lacrimal gland which were collected from No.2 Hospital of Tianjin Medical University from January 1991 to Jule 2011. There were 25 males and 35 females aged from 29 to 42 years. Based on histological revision, there were 36 cases of cribriform-tubular subtype and 24 cases of solid subtype. Forty-five cases were primary lesions and 15 cases were recurrent lesions. Ten samples of normal lacrimal gland around polymorphic adenoma were selected as the control group. The expression of CD105, MMP-2 and MMP-9 were evaluated by immunohistochemistry. The microvessel density (MVD) was defined by expression of CD105. One way ANOVA, χ(2)-test and spearman correlation test were used to analyzed the data. RESULTS: The number of MVD [(17.71 ± 5.63)/100 folds field of vision] and the positive rates of MMP-2 (45.0%, 27/60) and MMP-9 (55.0%, 33/60) in the samples of adenoid cystic carcinoma of lacrimal gland were higher than those in the normal lacrimal gland [the number of MVD was (0.70 ± 0.95)/100 folds field of vision, the expressions of MMP-2 and MMP-9 were negative] (t' = 2.039, P < 0.05; χ(2) = 5.550, P < 0.05; χ(2) = 8.315, P < 0.01), the solid subtypes had more MVD [(26.12 ± 5.32)/100 folds field of vision] and higher positive rates of MMP-2 (62.5%, 15/24) and MMP-9 (79.2%, 19/24) than the cribriform-tubular subtypes (t' = 2.060, P < 0.05; χ(2) = 4.950, P < 0.05; χ(2) = 9.439, P < 0.05); the recurrent lesions had more MVD and higher positive rate of MMP-2 and MMP-9 than the primary lesions (t' = 2.129, P < 0.05; χ(2) = 9.899, P < 0.05; χ(2) = 8.103, P < 0.05). The number of MVD in ACC of lacrimal gland patients was correlated with the positive rate of MMP-2 and MMP-9 respectively (rs = 0.636, P < 0.05; rs = 0.524, P < 0.05). CONCLUSIONS: The number of MVD and the expression of MMP-2 and MMP-9 are higher level in adenoid cystic carcinoma of lacrimal gland and are significantly correlated with pathological type and recurrence. Detecting the number of MVD and the expression of MMP-2 and MMP-9 may become biological indexes for malignancy, recurrence and metastasis of adenoid cystic carcinoma of lacrimal gland.

[Clinical diagnosis and curative effect observation of seventeen patients hemangiopericytoma in orbit].

OBJECTIVE: To conclusion the clinical features and image features, the diagnosis and management of orbital hemangiopericytoma, in order to direct clinical diagnosis and differential diagnosis. METHODS: Seventeen patients with pathologically confirmed orbital hemangiopericytoma were analyzed retrospectively. RESULTS: Patients usually complained of exophthalmos. Fourteen patients can be touched the tumor in the orbit. In B-scan ultrasound, a well outlined lesion was revealed. The type of it was often similarly circular or anomaly. The extent of internal echo was associated with histological structure of lesion. Color doppler flow imaging show that the tumor has rich feeding vessels. Some of them is arterial feeding vessels. On CT scan, hemangiopericytoma generally appears to be a uniform high-density mass with obvious enhancement upon injection of contrast material. All cases underwent surgical resection and are proved by pathological examination. CONCLUSIONS: Orbital hemangiopericytoma is a potentially malignant tumor. The prognosis and clinical behavior can't be predicted on the basis of their histopathologic classification. Medical imaging can help to demonstrate the site, configuration, and characteristics of the tumors and contribute to the treatment. But, there has not characteristic medical features. The final diagnosis must be depend on the pathology. The best management of hemangiopericytoma is complete local excision. All the patients must be observed nearly.

[Overexpression of the receptor tyrosine kinase EphA2 in choroidal melanoma: correlation with vesculogenic mimicry and prognosis].

OBJECTIVE: To study the correlation of EphA2 protein expression with vesculogenic mimicry (VM), clinicopathological characteristics and prognosis in choroidal melanoma (CM). METHODS: It was a retrospective case series study. Between January 1992 and December 2005, 56 cases of human CM with clinicopathologic data from the Second Hospital of Tianjin Medical University were studied. HE stainings were performed to observe the microcirculation patterns in tumor tissue specimens. VM was found in 26 of the 56 cases using CD31/periodic acid-Schiff (PAS) double staining and transelectron microscopy. All cases were divided into two groups: VM-positive and VM-negative. Immunohistochemical staining was performed on paraffin sections of the 56 cases of CM specimens to investigate the expression of EphA2. According to tumor cells positive rate and staining intensity of the results of evaluation, the specimens were divided into low expression and high expression groups.χ(2)-test and t-test were used to analyzed the enumeration data and measurement data, respectively. Survival analysis was used to further elucidate its correlation with clinicopathological characteristics, VM and prognosis. Cox proportional hazard model was used to analyzed the influence factors of prognosis. RESULTS: VM channels were found in 26 of the 56 CM cases and VM-negative 30 cases. VM-positivity was related to cell type, tumor size and recurrence and metastasis, and the differences were statistically significant (χ(2) = 4.612, 5.346, 5.213; P = 0.036, 0.021, 0.027). The results showed that EphA2 was up-regulated in the VM-positive group compared with the group of VM-negative group. The positive rates of EphA2 expression in the VM-positive group and VM-negative group were 92.3% (25/26) and 70.0% (21/30), respectively, with a significant difference between the two groups (t = 2.247, P = 0.009). The EphA2 protein was expressed in epithelioid (10/12), mixed (11/15) and spindle (41.40%) cell types, with a significant difference among these histological types (χ(2) = 6.513, P = 0.010). The expression rate of EphA2 protein were significantly higher in large (54.55%, 18/33) than small (45.45%, 15/33) tumors, and the expression of EphA2 in metastatic and recurrence patients (10/11) were significantly higher compared with controls (31.11%, 14/45) (χ(2) = 4.556, 8.211;P = 0.016, 0.005). Kaplan-Meier survival analysis showed the presence of VM resulted in a poor prognosis (t = 9.263, P = 0.000). The Cox proportional hazards model indicated that the EphA2 overexpression and the presence of VM were independent predictors of a poor prognosis (χ(2) = 12.041, P = 0.001). Moreover, there was a significant positive correlation between them (r = 0.412, P < 0.05). CONCLUSION: The results of this study demonstrate that EphA2 may play a critical role in the formation process of VM in CM, implicating EphA2 as a valuable marker for the prediction of recurrence, metastasis and prognosis in CM patients.

Enhanced Electrical Performance and Stability of Solution-Processed Thin-Film Transistors with In2O3/In2O3:Gd Heterojunction Channel Layer.

The use of the semiconductor heterojunction channel layer has been explored as a method for improving the performance of metal oxide thin-film transistors (TFTs). The excellent electrical performance and stability of heterojunction TFTs is easy for vacuum-based techniques, but difficult for the solution process. Here, we fabricated In2O3/In2O3:Gd (In2O3/InGdO) heterojunction TFTs using a solution process and compared the electrical properties with single-layer In2O3 TFTs and In2O3:Gd (InGdO) TFTs. The In2O3/InGdO TFT consisted of a highly conductive In2O3 film as the primary transmission layer and a subconductive InGdO film as the buffer layer, and exhibited excellent electrical performance. Furthermore, by altering the Gd dopant concentration, we obtained an optimal In2O3/InGdO TFT with a higher saturation mobility (µ) of 4.34 cm2V-1s-1, a near-zero threshold voltage (Vth), a small off-state current (Ioff) of 1.24×10-9 A, a large on/off current ratio (Ion/Ioff) of 3.18×105, a small subthreshold swing (SS), and an appropriate positive bias stability (PBS). Finally, an aging test was performed after three months, indicating that In2O3/InGdO TFTs enable long-term air stability while retaining a high-mobility optimal switching property. This study suggests that the role of a high-performance In2O3/InGdO heterojunction channel layer fabricated by the solution process in the TFT is underlined, which further explores a broad pathway for the development of high-performance, low-cost, and large-area oxide electronics.

[Clinical analysis of orbital chloroma].

OBJECTIVE: To analyze and summarize the clinical aspects, diagnostic methods and treatment principle of the orbit chloroma. METHODS: It was a retrospective case series study. The clinical aspects of 17 orbital chloroma cases were analyzed, which included symptoms, signs, imageology, diagnosis, treatment and prognosis. RESULTS: Orbit chloroma was more prevalent in males, and usually occurred in children and individuals under 14 years old. The main symptoms were exophthalmos and orbit masses. B ultrasonic examination was performed in 16 cases, which found that the mass was located in the temporal side of the orbit, with irregular shape and clear edge. Color doppler imaging was performed in 5 cases, which found that the sufficient blood supply signal was the main manifestation. CT scan was performed in 11 cases, which revealed that the mass was located in temporal side of the orbit, with irregular shape, regular density, a clear edge and seldom destruction of the orbital bone. Blood examination was performed in 17 cases, which revealed the increase of white blood cells and the presence of numerous immature blood cells. Sixteen cases were referred to the department of hematology for treatment. In 4 following cases, 2 cases were died within 3 months. CONCLUSIONS: Orbital chloroma can be easily misdiagnosed as other types of malignant orbital tumor in children. The diagnosis of orbital chloroma can be established by radiology and hematological examinations. This tumor can be treated by chemotherapy and radiotherapy.

Aberrantly expressed GFRα-1/RET in patients with lacrimal adenoid cystic carcinoma is associated with high recurrence risk: a retrospective study of 51 LACC cases.

Objective: Because of the poor prognosis of lacrimal adenoid cystic carcinoma (LACC), we aimed to investigate the effects of perineural invasion (PNI) and consequent aberrations in GDNF/GFRα-1/RET protein expression on LACC recurrence. Methods: Clinicopathological data for 51 histologically confirmed patients with LACC enrolled between 2001 and 2017 were retrospectively analyzed. Hematoxylin and eosin staining was applied to assess PNI. Tissue-based immunohistochemistry (IHC) detection of GDNF, GFRα-1, and RET proteins was performed on LACC formalin-fixed, paraffin-embedded specimens. We generated semi-quantitative data of the IHC results and compared them with the clinicopathological data for the 51 patients. Results: Of the 51 patients, 19 (37.3%) were PNI positive. Recurrence was more common for LACC with than without PNI (73.7% vs. 37.5%, P = 0.01). GDNF, GFRα-1, and RET proteins were expressed in 62.7%, 62.7%, and 54.9% of the 51 patients with LACC, respectively. The expression of all 3 proteins was more common in patients with than without PNI. In agreement with previous findings, PNI-associated GFRα-1 and RET positivity, as detected by IHC, remained significantly associated with recurrence, whereas GDNF expression, as detected by IHC, was not correlated with LACC recurrence. Specifically, patients with concurrent GFRα-1 and RET expression may have a high risk of PNI (89.5% positivity rate) and recurrence (84.2% positivity rate). Conclusions: PNI may contribute to LACC recurrence. The concurrent expression of GFRα-1 and RET proteins, as detected by IHC, may potentially be associated with LACC PNI and recurrence.

[Clinical analysis of primary extraocular muscles tumors].

OBJECTIVE: To analyze the clinical manifestation of primary extraocular muscles tumors and to study the diagnosis and therapy of this disorder. METHODS: Retrospective analysis of the clinical data of all primary extraocular muscles tumors (the diagnosis was confirmed by operation and pathological examination) in our hospital. RESULTS: There were 9 cases of primary extraocular muscle tumors. Six cases involved the internal rectus, 2 cases involved the external rectus, 1 case involved both inferior rectus and inferior oblique. Three cases involved the total length of the muscle; 2 cases involved the anterior muscle tendon and belly, 3 cases involved the posterior muscle tendon and belly, 1 case involved the muscle belly only. There were 3 cases of venous hemangioma, 2 cases of fibroangioma, 2 cases of neurilemoma, 1 case of fibrous histiocytoma and 1 case of paraganglioma. Image examination showed significant enlargement of extraocular muscle with clear boundary. B-scan ultrasonography, color Doppler flow image, CT and MRI scan showed different features. Patients were treated by excision of the tumor. Transplantation of the rectus was performed in several cases after the excision of the muscle. CONCLUSIONS: Vascular tumors are the most common type of primary extraocular muscle tumors. Congestion and swelling can be observed at the insertion of the rectus. The eyeball is proposed and moved to the opposite side of the affected muscle. Changes in the image analysis are related to the pathologic features. A good therapeutic results can be achieved by surgical excision of the tumor.

[Etiology, diagnosis and treatment analysis of 37 cases with orbital fistula].

OBJECTIVE: To present some instruction in diagnosis and treatment of the orbital fistula by analyze the clinical manifestation. METHOD: The clinical data for 37 cases with orbital fistula treated during 1980 to 2007 were analyzed retrospectively. RESULTS: Among 37 cases with orbital fistula, there are 21 cases caused by foreign bodies, including 17 cases by retained wooden bodies, 3 cases by iatrogenic foreign bodies and 1 case by firecrackers. There are 9 cases caused by orbital cysts, including 5 cases dermoid cysts, 3 cases epidermoid cysts and 1 case frontal mucopyocele. There are 6 cases orbital infection inflammation, including 5 cases osteomyelitis and 1 case orbital abscess. There is 1 case eosinophilic granuloma. Different etiologies have characteristic features. Medical history, fistula examinations and imaging examinations must be analyzed synthetically in order to make proper etiological diagnosis. Eradicate etiologies and resect fistula are most important. It is necessary to make an ancillary therapy, such as ENT treatment. CONCLUSIONS: The common etiologies of orbital fistula are retained foreign body, dermoid cysts and osteomyelitis. The pathogenesis include infective inflammation, congenital heteroplasia, operation and tumor. B-scan ultrasonography, CT, and MRI can be used for the localization and qualitation diagnosis. There are comprehensive approaches for diagnosis and management of this type of injury. In order to give an effective therapy, we must make an accurate diagnosis and analyze the features of fistula.

[Analysis of treatment and prognosis of orbital adenoid cystic carcinoma].

OBJECTIVE: To summarize the treatment outcomes of orbital adenoid cystic carcinoma and to evaluate prognostic factors. METHOD: A retrospective case series study was performed on 75 patients with orbital adenoid cystic carcinoma treated from 1991 to 2006. RESULTS: The 2- and 5-year local recurrence rate of solid type orbital adenoid cystic carcinoma was significantly higher than that of the adeno-tubiform type [2-year, 85% (17/20) vs 23.53% (8/34), chi(2) = 19.14, P = 0.000; 5-year, 100% (19/19) vs 64.52% (20/31), Fisher's exact test, P = 0.003]. The regional extension and distant metastasis of solid type were more than those of adeno-tubiform type. The 5-year local recurrence rate treated by postoperative radiation was lower than that treated with only surgical excision [70% (14/20) vs 92.86% (13/14); Fisher's exact test, P = 0.198]. The 5-year local recurrence rate in patients initially treated by orbital evisceration during the first time was lower than that of cases which evisceration procedure was used after the recurrence [25% (1/4) vs 75% (6/8), Fisher's exact test, P = 0.222]. Tumors may extend into intracalvarium, nasal cavity and temporal fossa. They may spread to the lung, bone, liver and lymph node. The 5-year metastasis rate was 25.71% (9/35). Both of the lung and bone metastasis rates were 33.33% (3/9). The overall 5-year accumulative survival was 74.29% (26/35), mortality was 25.71% (9/35), and rate of survival without tumor recurrence was 37.14% (13/35). The 10-year disease free survival rate was 17.14% (6/35). Patients were most likely to die with intracranial extension. Surgical excision with postoperative radiation improved the 5-year survival rate to 80% (16/20). CONCLUSIONS: Orbital adenoid cystic carcinoma is one of the most malignant tumors in the orbit. They have a high local recurrence rate and survival rate. Tumor histological types and the treatment procedure can influence the prognosis. Combined therapy may decrease the recurrence and increase the survival rate.

The Expression of Calprotectin and Factors in TLR4/NF-κB/MyD88 Pathway in Patients with Idiopathic Acute Anterior Uveitis.

Purpose: The purpose of the article is to investigate the contribution of calprotectin and factors in toll-like receptor 4/nuclear factor-κB/myeloid differentiation factor 88 (TLR4/NF-κB/MyD88) pathway in patients with idiopathic acute anterior uveitis (IAAU). Methods: In total, 72 patients with IAAU and 56 healthy individuals were enrolled. Serum calprotectin, TLR-4, and MyD88 were determined. Best-corrected visual acuity, uveitis activity grading, and macular thickness measured by optical coherence tomography were performed. Results: Serum calprotectin, TLR4, and MyD88 levels were higher in IAAU group than those in healthy individuals. Serum calprotectin level was positively correlated with uveitis activity grading and macular thickness. Receiver operating characteristic curve analysis showed serum calprotectin had larger area under curve than serum TLR4 and MyD88. Conclusions: The calprotectin and TLR4/NF-κB/MyD88 signal might contribute to the pathogenesis of IAAU and serum calprotectin might be a specific biomarker for the measurement of ocular inflammation in IAAU.

Volume-staged Gamma Knife radiosurgery for orbital venous malformations.

OBJECTIVEThis article is a preliminary evaluation of the efficacy of volume-staged Gamma Knife radiosurgery (GKRS) in the treatment of patients with orbital venous malformations (OVMs).METHODSTwenty patients with moderate to large OVMs were treated with volume-staged GKRS between March 2005 and October 2015. The series included 8 male and 12 female patients with an average age of 22.5 years (range 9-45 years). The diagnoses were confirmed intraoperatively and at pathological examination in 14 cases and presumed in accordance with clinical and imaging findings in 6 cases. The median OVM volume was 12.2 cm3 (range 7.1-34.6 cm3). The median interval between stages was 10 months (range 6-12 months). The tumor margin dose for each stage ranged from 11.0 to 13.5 Gy. The median duration of follow-up was 45.5 months (range 18-98 months).RESULTSPeriodically scheduled MRI studies demonstrated evidence of a significant reduction of the original OVM volume in all cases. Visual acuity (VA) was preserved in 18 cases (90%). Five patients (25%) experienced vision improvement of varying degrees, and 13 (65%) experienced long-term preservation of VA at their pre-GKRS level. Deterioration in VA was observed in only 2 cases (10%). MRI demonstrated OVM regression after treatment in all cases, and all patients were found to have reduction of exophthalmos after volume-staged GKRS. Follow-up MRI revealed recurrence in only 1 case (5%). Three patients (15%) developed transient conjunctival edema.CONCLUSIONSThis retrospective investigation indicates that volume-staged GKRS provides an effective management option in selected patients with OVMs, providing excellent visual outcomes. The study adds substantial support for volume-staged GKRS as a major treatment for OVMs.

Discriminating Value of Calprotectin in Disease Activity and Progression of Nonradiographic Axial Spondyloarthritis and Ankylosing Spondylitis.

It has been controversial whether ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (nr-axSpA) are separate or different phases of radiographic progression. We determined that serum calprotectin level (ng/ml) was higher in AS (15.30 ± 6.49) and nr-axSpA (17.76 ± 8.59) patients than in healthy individuals (7.40 ± 2.67). No difference was observed in calprotectin level between these two groups. Elevated calprotectin was positively correlated with ESR, CRP, BASDAI, and ASDAS as well as SPARCC scoring and had no correlation with BASFI and mSASSS. No correlation was observed between calprotectin and Wnt/ß-catenin pathway markers. Serum calprotectin can be used as a marker for inflammation in both nr-axSpA and AS, while it does not contribute to the discrimination of AS and nr-axSpA. Calprotectin-mediated inflammation was not correlated with principle effectors of Wnt/ß-catenin pathway, indicating that inflammation and bone fusion might be separate processes of the disease.

[Gene and protein expression of thyrotropin-receptor in retro-bulbar tissue from thyroid-associated ophthalmopathy].

OBJECTIVE: To investigate gene and protein expression level of thyrotropin-receptor (TSHR) in retro-bulbar connective tissue and fat tissue in patients with thyroid-associated ophthalmopathy (TAO). METHODS: Retro-bulbar tissues specimens were obtained from 11 cases of TAO patients and 10 control cases during the operation. RNA was extracted from the tissue specimens using single-step method of acid guanidinium-thiocyanate-phenol-chloroform extraction and TSHR mRNA was analyzed by reverse transcription polymerase chain reaction (RT-PCR). Immunochemistry staining was performed in patients expressed TSHR, using a mouse polyclonal anti-TSHR peptide antibody to observe protein expression level of TSHR. RESULTS: The size of TSHR mRNA segment is 521 bp. The rate of TSHR mRNA expression in TAO retro-bulbar tissue was 91% and was 20% in the control cases, the former was significantly greater than the later. Protein expression rate was 66.7% in TAO patients, and was negative in the controls. CONCLUSIONS: High TSHR mRNA expression level and protein level in TAO retro-bulbar tissue and no expression in control tissue indicate that TSHR exists as a common antigen in the orbit and thyroid, and plays a key role in the pathogenesis of TAO.

Alteration of Bone Turnover Markers in Canonical Wingless Pathway in Patients With Ankylosing Spondylitis.

OBJECTIVES: This study aims to determine the levels of bone turnover markers in canonical wingless pathway in patients with ankylosing spondylitis (AS) and the correlation with disease activity indexes. PATIENTS AND METHODS: We recruited a total of 43 AS patients (34 males, 8 females; mean age 36.8±9.3 years; range 22 to 62 years) and age- and sex-matched 42 healthy controls (32 males, 10 females; mean age 36.1±9.7; range 24 to 59 years). Serum levels of components of canonical wingless pathway including Dickkopf-1, glycogen synthase kinase-3ß, ß-catenin, alkaline phosphatase, and osteocalcin were detected using enzyme- linked immunosorbent assay method. All patients were assessed in terms of erythrocyte sedimentation rate, C-reactive protein, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, Ankylosing Spondylitis Disease Activity Score, and the modified Stoke's Ankylosing Spondylitis Spine Score. Pearson's correlation test was used to analyze the correlation between serum bone turnover markers and clinical assessment indexes. RESULTS: No significant difference was observed between AS patients and healthy controls for the levels of glycogen synthase kinase-3ß, ß-catenin, alkaline phosphatase, and osteocalcin, respectively (p>0.05). The level of Dickkopf-1 was significantly higher in AS patients (1914.5±407.8 pg/mL) than in healthy controls (1729.1±352.9 pg/mL) (p<0.05). There was no correlation between high Dickkopf-1 level and any of the clinical parameters contributing to inflammation or bone formation. However, the correlation between osteocalcin and disease duration was significant in AS patients (r=0.323, p=0.034). CONCLUSION: Alteration of bone turnover markers in canonical wingless pathway was observed in AS. This might partially explain the complicated mechanism of bone formation in the disease.

Rapid reduction of antibodies and improvement of disease activity by immunoadsorption in Chinese patients with severe systemic lupus erythematosus.

This was an exploratory analysis comparing the safety and efficacy of immunoadsorption (IAS) combination therapy in severe systemic lupus erythematosus (SLE) receiving corticosteroid pulse and immunosuppressant treatment. Patients enrolled all had predominant organ involvement including proteinuria, thrombocytopenia, pericardial effusion, and cerebral involvement requiring corticosteroid pulse treatment. Fifty-two patients in study group received IAS plus corticosteroid and cyclophosphamide treatment. Fifty-two patients in non-IAS group received corticosteroid and cyclophosphamide treatment. Outcome measurement included C3, dsDNA, AnuA, and SLE disease activity index (SLEDAI) 2k score and in particular cases, proteinuria quantification and platelet count. Disease activity dropped significantly in both groups. Improvement of disease activity markers was more significant in study group than that in non-IAS group. The lower dosage of steroid in study group suggested the steroid-sparing effect of IAS. No severe adverse effect occurred during IAS. Our study suggested IAS as an additional therapy to steroid pulse and immunosuppressant in treating severe SLE.

[Recent advances in the studies of orbital diseases].

Orbital diseases are not common, but they are closely related with various systems of the body. A significant progress in orbital diseases has been achieved both in China and abroad in the last several years. The study of etiology of thyroid-associated ophthalmopathy and the establishment of an experimental animal model have provided the hope for a novel treatment of this disease; the studies of rhabdomyosarcoma and tumors of lacrimal gland at the molecular level have provided the basis for the development of a novel treatment; new plaque radiotherapy and application of various kinds of seed have enriched the treatment and improved the prognosis of orbital tumors. Some significant progresses, for example, a new viewpoint of meningioma of the optic nerve sheath and glioma, improved approach for entering the orbit and complex treatment of malignant tumors have revealed a new path for the diagnosis and treatment of orbital disease.