Mortality associated with polymyalgia rheumatica in the United States in the 1999-2020 period: a multiple-cause-of-death study.

OBJECTIVE: Multicause-of-death methods were used to analyze mortality and leading causes of death associated with polymyalgia rheumatica (PMR) in the United States from 1999 to 2020. MATERIALS AND METHODS: We analyzed mortality data from the Centers for Disease Control and Prevention (CDC) Data analysis system and selected death certificates that listed PMR as the cause of death based on the International Statistical Classification of Diseases and Related Health Problems (ICD-10) category code. Relevant mortality rates, number of deaths and historical trends were analyzed. The number of PMR-related deaths and age-standardized mortality rate (ASMR) trend charts were made using Excel 2010 version and trend lines were added. RESULTS: Over the last 22 years, the total number of PMR-related deaths in the United States was 15,421 women (89.8%), a ratio of about 1:9 men to women. When PMR is listed as the underlying cause of death, the ASMR for women and men (per 100,000 people) is approximately 1.8-5.1:1, and when it is listed as the non-underlying cause of death, it is 1.8-3.3:1. PMR deaths are more frequent in individuals aged 70 years and above, with patients aged 80 years and above being most affected. Among different ethnicities, the highest number of deaths was found in Caucasians, followed by Black or African American. When it comes to causes of death, heart disease still ranks first, followed by cancer. In addition, we also found that when PMR combined with malignant tumors as a multiple cause of death, the number of female deaths was higher than that of male deaths, the overall number of deaths of both showed an upward trend, and the overall ASMR of both showed a downward trend. CONCLUSIONS: In the past 22 years, we have observed a low mortality rate of PMR in the United States. However, for patients with PMR, especially elderly women, medical workers should be vigilant and pay attention to whether they are combined with other complications, such as malignant neoplasms, and make timely diagnosis and treatment to further reduce the mortality rate of patients with PMR.

[Clinical pathological and genetic mutation characteristics of conjunctival lymphoepithelial carcinoma].

Objective: To analyze the clinical pathological and genetic mutation characteristics of conjunctival lymphoepithelial carcinoma. Methods: A retrospective case series study was conducted. Data from three patients diagnosed with conjunctival lymphoepithelial carcinoma and treated with tumor resection surgery at Tianjin Eye Hospital from January 2006 to December 2022 were collected. Four paraffin specimens (including one patient undergoing two surgeries) were subjected to immunohistochemical staining for epithelial antigen and lymphocytic antigen. Epstein-Barr virus (EBV)-encoded RNA (EBER) was detected using in situ hybridization, and whole-exome sequencing was performed on three specimens from two patients using next-generation sequencing methods. Results: All three patients were males aged over 65, with a disease duration ranging from 3 to 44 months. The tumors were unilateral, located on the bulbar or limbal conjunctiva, appearing red, with a maximum diameter of 4-20 mm. Imaging examinations revealed anterior location of the tumors with no involvement of the orbital bone, extraocular muscles, optic nerve, or paranasal sinuses. No local lymph node metastasis was observed in any patient. Pathological findings included undifferentiated carcinoma nests with significant reactive lymphocytic and plasma cell infiltration. Tumor cells were positive for pan-cytokeratin (CK-pan), epithelial membrane antigen (EMA), tumor protein 40 (p40), and tumor protein 63 (p63), with a cell proliferation index (Ki67) exceeding 80%. Cluster of differentiation 20 (CD20), CD3, and CD8 were positive for lymphocytes. In situ hybridization showed partial tumor cell expression of EBER in two specimens of one patient. Whole-exome sequencing revealed 58, 50, and 36 mutated genes in the three specimens, with enriched signaling pathways including melanoma signaling pathway, Notch1 signaling pathway, and RHOQ GTP cycle; enriched biochemical processes included amino acid starvation response, programmed cell death, regulation of lipid synthesis, sodium ion transport, and chromosome segregation. The common mutated gene in all three specimens was SZT2, and SZT2 was involved in the amino acid starvation response. One patient underwent a second complete resection surgery 40 months after partial excision, while the other two underwent complete resection surgery without recurrence. Two patients did not undergo radiation or chemotherapy, and one was lost to follow-up. Conclusions: Conjunctival lymphoepithelial carcinoma is associated with prominent lymphocytic and plasma cell infiltration, some cases are associated with EBV infection, and SZT2 mutations are present in conjunctival lymphoepithelial carcinoma.

[Clinical pathological characteristics analysis of ocular adnexal follicular lymphoma].

Objective: To investigate the clinical pathological characteristics of ocular adnexal follicular lymphoma (OAFL). Methods: A retrospective case series study was conducted. Clinical data of 10 OAFL patients diagnosed at Tianjin Eye Hospital from January 1990 to May 2022 were collected. The study analyzed general patient information, medical history, site of involvement, imaging, histopathology, and molecular detection. Among them, 7 cases underwent Epstein-Barr virus-encoded small RNA (EBER) and B-cell lymphoma protein 2 (BCL-2)/immunoglobulin heavy chain gene (IgH) translocation gene detection. Treatment and prognosis of patients were followed up. Results: All 10 patients (10 eyes) had unilateral involvement, including 5 males and 5 females, with an age range of 58 (43, 68) years. Clinical manifestations included eyelid swelling, pink conjunctival thickening, painless slow-growing masses in the lacrimal gland area, extraconal muscle cone, conjunctiva, lacrimal sac, or a combination of lacrimal sac and conjunctiva. Among them, 8 cases were primary, and 2 cases were secondary. According to the Ann Arbor staging, 8 cases were stage Ⅰ-Ⅱ E, and 2 cases were stage Ⅲ E. Histopathological grading revealed 6 cases of grade 1-2 and 3 cases of grade 3A. One case showed grade 3B in the lacrimal sac area and grade 1-2 in the conjunctiva. The predominant subtype was follicular in 4 cases, diffuse in 3 cases, and mixed in 2 cases. One case had a mixed subtype involving the lacrimal sac and conjunctiva. All patients expressed positivity for leukocyte differentiation antigens (CD) 20, CD21, and CD23. Nine cases were positive for CD10, with 1 case showing partial CD10 positivity. All patients were positive for B-cell lymphoma protein 6 (BCL-6), and 9 cases were positive for BCL-2. Specific markers CyclinD1 and Multiple Myeloma Oncogene Protein 1 (MUM-1) were negatively expressed in all cases. The Ki-67 proliferation index ranged from 10% to 90%. Molecular detection was performed in 7 patients, with none showing positive EBER in situ hybridization. However, 5 cases exhibited BCL2/IgH gene fusion. Among 7 patients with follow-up data, the median follow-up time was 17 (6, 34) months. Four patients achieved complete remission, 2 had partial remission, and 1 patient died due to lung infection. Conclusions: OAFL is a tumor originating from follicular center B-cells, characterized by positive expression of BCL-2, CD10, and BCL-6. It can involve the lacrimal gland, extraconal muscles, lacrimal sac, and conjunctiva. Patients generally have a favorable prognosis.

[Clinical characteristics analysis of patients with severe immune checkpoint inhibitors related myocarditis].

Objective: To analyze the clinical characteristics of patients with severe immune checkpoint inhibitors (ICIs) related myocarditis. Methods: A retrospective study was conducted on the 50 patients with ICIs-related myocarditis in the multidisciplinary cardio-oncology clinic of Zhongshan Hospital affiliated to Fudan University from April 2020 to April 2022. The age of patients was (63.7±10.8) years old, including 37 males and 13 females. The patients were divided into the mild group (n=37) and the severe group (n=13) according to severity. The differences of basic characteristics, clinical manifestations, laboratory tests, auxiliary examination, combined irAEs, treatment and outcomes between the two groups of patients were analyzed. Results: The immunotherapy time [M(Q1,Q3)] of patients in the mild group and severe group were 81 (49, 134) and 24 (20, 116) days, respectively (P<0.05). In the severe group, the levels of cTnT [0.605 (0.317, 1.072) µg/L], NT-proBNP [1 126 (386, 1 744) ng/L], CK-MB [78 (48, 238) U/L], and CK-MM [240 (45, 6 543) U/L] were higher than those in the mild group [0.104 (0.045, 0.189) µg/L, 237 (39, 785) ng/L, 24 (20, 33) U/L, 108 (72, 168) U/L, respectively] (all P<0.05). The left ventricular ejection fraction of the severe group [64% (57%, 65%)] was lower than that of the mild group [66% (63%, 69%)] (P<0.05), and the incidence of conduction block (n=4, 4/13) and abnormal ventricular wall motion (n=4, 4/13), the incidence of ICIs-related myositis (n=10, 10/13), ICIs-related hepatitis (n=4, 4/13) and ICIs-related neurotoxicity (n=4, 4/13) were higher than those in the mild group (n=1, 2.7%; n=2, 5.4%; n=16, 43.2%; n=2, 5.4%; n=1, 2.7%, respectively) (all P<0.05). The proportion of patients receiving intensified immunosuppressive therapy and mortality rate in the severe group were 12/13 (n=12) and 4/13 (n=4), which were both higher than those in the mild group [10.8% (n=4) and 0] (both P<0.05). Conclusions: The incidence of ICIs-related myocarditis is not high, but the severe rate and mortality are high. The differential diagnosis of severe ICIs related myocarditis should be combined with myocardial markers, electrocardiogram and echocardiogram, and early diagnosis and treatment can improve the prognosis of patients.

[Clinical and pathological analysis of 35 cases of ocular adnexal solitary fibrous tumor].

Objective: To analyze the clinical and pathological characteristics and prognosis of 35 cases of solitary fibrous tumor of ocular adnexal (SFT). Methods: This was a retrospective case series study. The clinical data of 35 cases of ocular adnexal SFT was collected in Tianjin Eye Hospital from January 2000 to December 2020. The clinical manifestations, imaging examination results, pathological characteristics, treatment of patients were analyzed, and patients were followed up. All cases were classified according to the 2013 classification of World Health Organization of tumors of soft tissue and bone. Results: There were 21 males (60.0%) and 14 females (40.0%). The age range was 17 to 83 years, and the median age was 44 (35, 54)years. All patients were unilateral, with 23 (65.7%) in the right eye and 12 (34.3%) in the left eye. The course of disease ranged from 2 months to 11 years, with an a median duration of 12(6,36)months. Clinical manifestations included exophthalmos, limited eye movements, diplopia, and tearing. All patients underwent surgical treatment of complete resection of the tumor. Ocular adnexal SFT mostly occurred in the upper orbit (19 cases, 73.1%). On imaging examination, the tumor showed well-circumscribed space occupying lesion that heterogeneously enhanced with contrast, and abundant blood flow signals in the tumors. MRI showed isointensity or low signal on T1WI, and significantly enhanced on T2WI, presenting intermediate-to-high heterogeneous signals. The tumor diameter was 2.1 (1.5, 2.6) cm. There were 23 cases (65.7%) of classic subtype, 2 cases (5.7%) of giant cell subtype, 8 cases (22.9%) of myxoid subtype, and 2 cases (5.7%) of malignancy. Immunohistochemical staining showed that Vimentin, CD34 and STAT6 were positively expressed in all patients. Twenty-one cases (60.0%) showed positive expression of BCL-2, and Ki-67 positive index ranged from 1.0% to 10.0%. Tumors in this group were all low-risk according to the Demicco risk stratification. Follow-up was available for 25 patients with a duration of 2 years to 14 years and 7 months, and the median follow-up time was 88 (61, 124) months. Two patients relapsed, and no distant metastasis or death was observed. Conclusions: Ocular adnexal SFT mainly presents as a painless, slow-growing mass. And most of them are typical SFT. The imaging manifestations are varied Ocular adnexal SFT generally follows a benign course, with a good prognosis after complete excision. Recurrence could occur many years after surgery which requiring careful and long-term follow-up.

[The clinicopathological features of adult orbital xanthogranulomatous disease with lacrimal gland reactive lymphoid hyperplasia].

Objective: To investigate the clinicopathological features of adult orbital xanthogranulomatous disease (AOXGD) with lacrimal gland reactive lymphoid hyperplasia. Methods: Retrospective case series study. The clinical and pathological data of AOXGD cases diagnosed and treated in Tianjin Eye Hospital from January 2002 to December 2021 was reviewed, and the clinical characteristics, radiologic findings and pathological characteristics of periocular and lacrimal gland lesions of 5 cases were retrospectively analyzed. The expression of IgG4 and IgG protein in periocular and lacrimal gland lesions was detected by immunohistochemical staining, and the role of IgG4 in AOXGD was preliminarily studied. Results: There were four females and one male with an average age of 53.8 years (39 to 77 years). Among the five AOXGD cases, there were three cases of adult-onset xanthogranuloma, one case of adult-onset asthma and periocular xanthogranuloma, and one case of necrobiotic xanthogranuloma. All cases involved both eyes. The swelling of eyelids was observed in five cases, and the yellow or pale yellow eyelid skin was found in two cases. Imaging examinations showed the tumor mainly involved the eyelids, subcutaneous tissues, anterior orbit and lacrimal gland. A large number of foam cells and typical Touton giant cells were found in the periorbital lesions, accompanied by different degrees of fibrosis. The fibrinoid necrosis was detected in one case of necrobiotic xanthogranuloma. The lacrimal gland lesions showed different types of reactive lymphoid hyperplasia, including IgG4-related disease in two cases, follicular lymphoid hyperplasia in two cases and focal lymphoid hyperplasia in one case. IgG4 levels of periorbital and lacrimal gland lesions were elevated in four cases. Asthma and elevated serum IgG4 were found in one case of adult-onset periocular xanthogranuloma. Three patients underwent surgical resection and adjuvant hormone or immunosuppressive therapy, and two patients underwent simple surgical resection. The patients were followed up for 1.5 to 10.0 years, one patient was lost, and four patients had no recurrence. Conclusions: AOXGD with lacrimal gland reactive lymphoid hyperplasia is a group of rare diseases. The periorbital lesions of that are characterized by proliferation of foamy histiocytes and Touton giant cells, and the lacrimal gland lesions of that manifest as IgG4-related disease in some cases.

Clinical and histologic features associated with lentigo maligna clearance after imiquimod treatment.

BACKGROUND: Imiquimod cream may be used as a non-surgical treatment for lentigo maligna or as adjuvant therapy following excision to decrease the risk of recurrence. OBJECTIVES: To evaluate histologic and clinical factors associated with clinical clearance of lentigo maligna treated with imiquimod. METHODS: We performed a retrospective review of all patients diagnosed with lentigo maligna and treated with imiquimod between 1997 and 2019 at our academic institution. RESULTS: We observed clinical clearance in 93% (66/71) of participants who received adjuvant imiquimod following surgery and 79% (19/24) in the primary non-surgical treatment group over a median of 38 months of follow-up. In the adjuvant therapy group, positive surgical margins were associated with a decreased rate of clinical clearance when compared to cases with close (<1 mm) margins or background melanocytic dysplasia (83.3 vs. 100%, p = .01). The presence of an inflammatory response during treatment was associated with increased clearance (94.1 vs. 66.7%, p = .02). CONCLUSIONS: Adjuvant imiquimod treatment may decrease LM recurrence rates in cases with background melanocytic dysplasia or close margins. LM cases with positive surgical margins need close clinical follow-up given higher recurrence rates.

[Clinical and pathological analysis of ocular adnexal diffuse large B-cell lymphoma].

Objective: To summarize the clinical and pathological characteristics of diffuse large B-cell lymphoma of ocular adnexal (OA-DLBCL). Methods: A retrospective case series study. Twenty-three cases of OA-DLBCL were collected in Tianjin Eye Hospital from January 2005 to December 2018. The clinical manifestations and imaging examination results were analyzed. The pathological characteristics and immune subtypes were analyzed with hematoxylin and eosin staining and immunohistochemistry. Eighteen patients completed the follow-up. Overall survival (OS) time was from the date of diagnosis to the date of death or the final follow-up (April 30, 2020). Clinical stages were analyzed by the Ann Arbor classification; Kaplan-Meier plots were used to visualize survival outcomes. The different risk groups were compared using Log-rank test. Results: There were 13 males and 10 females. The median age was 65 years (range, 43 to 82 years). Twenty-two patients had unilateral lymphoma (14 left eyes, 8 right eyes), and one patient had bilateral lymphoma. The OA-DLBCL was in the orbit in 14 patients, in the lacrimal gland in two patients, in both the lacrimal gland and the orbit in three patients, in both the lacrimal sac and the orbit in one patient, in the conjunctiva in one patient, in both the conjunctiva and the orbit in one patient, and in the skin of eyelids in one patient. Imaging examinations showed the tumors were of irregular soft tissue density. MRI showed the tumors were close to the extraocular muscles or ectocinerea. Centroblastic morphology was present in 21 specimens, and 2 specimens had immunoblastic morphology. Six patients were of germinal center B cell-like (GCB) type, and 17 were of non-GCB type. There were 2 patients with double expression of cellular-myelocytomatosis viral oncogene and B-cell lymphoma 2. The follow-up time ranged from 25 to 156 months, and the median follow-up time was 48 months. Five of them had primary OA-DLBCL, and 13 patients had secondary OA-DLBCL. Five patients were at the Ann Arbor clinical stage ⅠE, one was at stage ⅢE, and 12 were at stage ⅣE. During the follow-up, 8 patients survived, and 10 died. The 1-, 3-, and 5-year OS rates were 88.9%, 71.4% and 41.7%, respectively. Log-rank analysis indicated that the Ann Arbor clinical stage and age were related to the OS of OA-DLBCL (χ²=7.448, 8.804; both P<0.01). The gender, tumor size, molecular typing, Ki-67 index, and bone invasion were not related to the OS of OA-DLBCL (all P>0.05). Conclusions: OA-DLBCL mainly occurrs in the elderly population, unilaterally, and in the orbit. Most molecular types are non-GCB subtypes. The Ann Arbor clinical stage and age are associated with prognosis. (Chin J Ophthalmol, 2021, 57: 366-371).

[Clinical and pathological analysis of 64 patients with primary neoplasms of the lacrimal drainage system].

Objective: To analyze the pathological classification and age distribution of primary neoplasms of the lacrimal drainage system. Methods: Retrospective case series study. A total of 64 patients (65 eyes) were diagnosed with primary neoplasms of the lacrimal drainage system and received surgery at Tianjin Eye Hospital from January 2006 to December 2016. All the clinical data of the patients were analyzed, including gender, diseased eye, age, clinical manifestations, composition of benign and malignant masses, and prognosis. The histopathological composition and age distribution of patients with primary lacrimal mass, lacrimal duct mass and lacrimal sac mass were analyzed according to the different diseased sites. Results: Twenty-three patients (24 eyes) were male, and 41 patients (41 eyes) were female. The right eye was involved in 36 patients, the left eye in 27 patients, and both eyes in one patient. The age at diagnosis ranged from 12 to 78 years old [mean, (46±4) years]. The course of disease was (13.1±4.2) months, ranging from 1 month to 7 years. The chief complaint was tear discharge in 43 patients, tumor in 19 patients, and abscess discharge in 2 patients. There were 29 patients with angular displacement and 21 patients with swelling pain. There were 51 patients with benign lesions, 4 with borderline lesions, and 9 with malignantlesions. These neoplasms consisted of primary peripunctal neoplasms in 17 patients, primary canalicular neoplasms in 2 patients, and primary lacrimal sac neoplasms in 45 patients. All primary peripunctal neoplasms (17 cases) were benign, among which nevi (10 cases) occupied the first place. All primary canalicular neoplasms (2 cases) were benign, there were 1 case of epidermoid cysts and 1 case of degenerative disease. Among the primary benign lacrimal sac masses (32 cases), mucous epithelial cysts (9 cases), dermoid cysts (6 cases), and epidermoid cysts (6 cases) occupied the first three places. Among the primary borderlin lacrimal sac masses (4 cases), there were 2 cases of giant cell tumor of soft tissue, 1 case of solitary fibrous tumor, and 1 case of inflammatory myofibroblastic tumor. The primary malignant mass of lacrimal sac (9 cases) was dominated by squamous cell carcinoma (3 cases). In terms of age distribution, the patients with primary peripunctal mass were mainly in the group of 40-59 years old (14 cases). The primary benign mass of lacrimal sac mainly occurred in the group of less than 40 years old (15 cases) and the group of 40-59 years old (11 cases). The patients with primary lacrimal sac borderline and malignant masses were all in the groups of over 40 years old. A total of 49 patients were followed up for 27 months to 16 years. The average follow-up time was (57.2±3.8) months. Lacrimal sac transitional cell carcinoma relapsed 7 months after surgery in one patient, and lacrimal sac melanoma relapsed 1 year after surgery in one patient. The patients did not relapse in 24 months and 38 months after surgery respectively. There were no recurrence of other cases. Conclusions: Primary peripunctal neoplasms are mostly characterized with benign lesions, among which nevi are most common. Mucous epithelial cysts, epidermoid cysts, and dermoid cysts are the major benign lacrimal sac neoplasms. Squamous cell carcinomas are the most common malignant lacrimal sac neoplasms. The malignant tumor of lacrimal sac often occurs in the middle-aged and elderly patients. (Chin J Ophthalmol, 2020, 56: 364-369).

[Clinical and pathological study on IgG4-related ophthalmic disease involving the lacrimal gland].

Objective: To summarize the clinical and pathological characteristics of IgG4-related ophthalmic disease (IgG4-ROD) involving the lacrimal gland. Methods: A retrospective case series study. Forty cases (56 eyes) of lacrimal gland lesions were collected in Tianjin Eye Hospital from January 2003 to January 2018 and confirmed by histopathology as lymphocyte and plasma cell infiltration with fibrosis of lacrimal gland tissue, excluding lymphoma, epithelial tumor, mesenchymal tumor and metastasis tumor. The clinical manifestations, serological and imaging examination of the patients were analyzed. Meanwhile, HE staining and immunohistochemical staining of IgG and IgG4 were performed on the pathological specimens. According to the diagnostic criteria, the cases were divided into the IgG4-ROD group and the non-IgG4-ROD group. The clinical and pathological characteristics of the two groups were statistically analyzed by Pearson chi-square and signed-rank test. Results: In the 40 cases (56 eyes), there were 15 cases (25 eyes) of IgG4-ROD and 25 cases (31 eyes) of non-IgG4-ROD. Statistically significant differences were observed between the two groups in the clinical and pathological characteristics (all P<0.05). About the distribution of eyes position, there were 10 binocular cases and 5 monocular cases in the IgG4-ROD group, and 6 binocular cases and 19 monocular cases in non-IgG4-ROD group (χ2=7.111).There were 21 eyes in the IgG4-ROD group and 5 eyes in the non-IgG4-ROD group about ptosis (χ2=25.631), 4 eyes in the IgG4-ROD group and 21 eyes in the non-IgG4-ROD group about ocular protrusion (χ2=14.992), 23 eyes in the IgG4-ROD group and 15 eyes in the non-IgG4-ROD group about the clear boundary of the tumor (χ2=12.069), 4 eyes in the IgG4-ROD group and 18 eyes in the non-IgG4-ROD group about the involvement of other orbital tissues (χ2=10.266) and 7 cases in the IgG4-ROD group and 3 cases in the non-IgG4-ROD group about the association with other systemic diseases (χ2=6.009). Compared with the non-IgG4-ROD group, the IgG4-ROD group had a heavier lymphocyte and plasma cell infiltration (+++,++,+; 10, 4, 1 vs. 6, 5, 12 eyes, Z=-3.153), and more lymphoid follicles (+++,++,+; 3, 6, 4 vs. 1, 2, 7 eyes, Z=-3.339), interstitial fibrosis was mostly striate (10 vs. 5 eyes, χ2=8.711), and there were a large number of IgG4+ plasma cells [96 (67, 135) vs. 4 (0, 12) cells per high power field, Z=-5.271] and ratio of IgG4+ plasma cells/IgG+ plasma cells [0.570 (0.500, 0.754) vs. 0.046 (0.000, 0.143), Z=-5.268, all P<0.05). Among the 10 cases of IgG4-ROD with serological examination, 9 cases showed elevated serum in IgG and IgG4. The ultrasonography and CT findings showed the lacrimal gland lesions in the IgG4-ROD group were mostly spindle or kidney shaped with clear boundaries, while the lesions in non-IgG4-ROD were mostly round or irregular with unclear boundaries. Conclusions: The lacrimal gland lesions of IgG4-ROD are characterized by bilaterally spindle or kidney shaped enlargement with clear boundaries. They are more associates with other systemic diseases. The pathological characteristics are a large number of IgG4+ plasma cells infiltration among the lacrimal gland tissue, interstitial striate fibrosis and a large number of lymphoid follicles. (Chin J Ophthalmol, 2019, 55: 834-841).

[The clinicopathological features and HPV detection of conjunctival actinic keratosis].

Objective: To describe the clinicopathological features of conjunctival actinic keratosis (AK) and relation to the infection of human papillomavirus (HPV). Method: Retrospective case series study. Eighteen cases (18 eyes) of conjunctival AK were obtained in Tianjin Eye Hospital and Institute (2005-2018). The clinical and histopathological features were studied. HPV was detected by a modified general primer HPV polymerase chain reaction (PCR) system in all formalin-fixed, paraffin-embedded specimens. Results: The male to female ratio was 5∶1. The mean age at diagnosis was 60 years (range: 43-79 years). Sixteen cases were located in the nasal interpalpebral region, and two cases were located in the temporal interpalpebral region. All cases were located in corneal limbus, and the mean distance of corneal invasion was 2 mm (range, 1-4 mm). The mean diameter was 4.6 mm (range, 2.0-8.0 mm). Clinically, most lesions (16 cases) appeared as a white or milky, flat plaque with clear borderline and conjunctival hyperemia; a few lesions (2 cases) showed a brown-black mass, partially white. Pathologically, conjunctival AK was a proliferation of epithelium with prominent parakeratosis or hyperkeratosis, stratum spinosm thickening and basal cell proliferation. Many AKs show solar elastosis and a mild inflammatory infiltrate of lymphocytes and plasma cells in the stroma. Most lesions (15 cases) were hypertrophic type, two cases were pigmented type, and one case was acantholytic type. HPV was negative in 18 cases. All case were removed by complete surgical excision. The rage of follow-up period was 1.0-10.4 years, ten cases were recorded, and no case recurred after surgical excision. Conclusions: Conjunctival AK is epithelial precancerous lesion that occurs in the keratoconjunctival margin. HPV infection might not be a causative factor in conjunctival AK. (Chin J Ophthalmol, 2019, 55: 531-535).

IGFBP2 promotes vasculogenic mimicry formation via regulating CD144 and MMP2 expression in glioma.

Vasculogenic mimicry (VM) refers to the fluid-conducting channels formed by aggressive tumor cells rather than endothelial cells (EC) with elevated expression of genes associated with vascularization. VM has been considered as one of the reasons that glioblastoma becomes resistant to anti-VEGF therapy. However, the molecular basis underlying VM formation remains unclear. Here we report that the insulin-like growth factor-binding protein 2 (IGFBP2) acts as a potent factor to enhance VM formation in glioma. Evidence showed that elevated IGFBP2 expression was positively related with VM formation in patients with glioma. Enforced expression of IGFBP2 increased network formation of glioma cells in vitro by activating CD144 and MMP2 (Matrix Metalloproteinase 2). U251 cells with stable knockdown of IGFBP2 led to decreased VM formation and tumor progression in orthotopic mouse model. Mechanistically, IGFBP2 interacts with integrin α5 and ß1 subunits and augments CD144 expression in a FAK/ERK pathway-dependent manner. Luciferase reporter and ChIP assay suggested that IGFBP2 activated the transcription factor SP1, which could bind to CD144 promoter. Thus, IGFBP2 acts as a stimulator of VM formation in glioma cells via enhancing CD144 and MMP2 expression.

[Clinicopathological study on conjunctival osseous choristoma].

Objective: To summarize the clinical pathologic characteristics of conjunctival osseous choristoma. Methods: Retrospective case series study. Six cases of conjunctival osseous choristoma between January 2009 and June 2016 from Tianjin Eye Hosptial were reviewed retrospectively. The clinical features, CT characteristics and histological characteristics were analyzed. Results: The 6 cases includes 3 male patients and 3 females. The age of the patients ranged from 4 to 20 years. Three cases involved with the right eye and the other 3 involved with the left eye. Major clinical feature of the patient is the flat uplift tumor in the superior temporal quadrant of the conjunctiva. CT features of conjunctival osseous choristoma revealed a oval calcium spot of eyeball surface. All the patients received surgery. Pathological examination showed that the tumor is composed of bone tissue which was surrounded by fibrous tissue, and Haversian canals are present in compact bone tissue. Five patients were followed for 23 months to 8 years. None of the patients relapsed after operation. Conclusions: The major feature of conjuncital osseous choristoma is a tumor in the superior temporal quadrant of conjunctiva. Imaging examination reveals a oval calcium spot of eyeball surface. Pathological examination reveals that the osseous tumor is composed of compact bone tissue which was surrounded by fibrous tissue.Haversian canals are present in compact bone tissue.Diagnosis is dependent on histopathological examination. It is not prone to relapse after complete resection surgery. (Chin J Ophthalmol, 2018, 54: 661-664).

[Clinical analysis of orbital ectopic meningiomas].

Objective: To investigate the clinical features, imaging features, diagnoses and therapeutic regimens of orbital ectopic meningiomas. Methods: A retrospective study. All the clinical data of 10 patients (10 eyes) with orbital ectopic meningiomas were analyzed retrospectively from August 1999 to October 2016. They included imaging data such as color Doppler ultrasound, CT and MRI, and information of diagnosis, pathology, therapeutic regimen and prognosis. Results: The age of orbital ectopic meningiomas was 7 to 68 years old. There were 4 males and 6 females. The clinical manifestations were mainly with swollen eyelid (8 cases), exophthalmos (7 cases), visual impairment (2 cases) and accidentally found a mass in the orbit with physical examination(2 cases). The tumor was located in (5 cases) or outside (5 cases) the muscular funnel of the orbit. The imaging features of CT included the irregular shape, unclear border, and extraocular muscular adhesions (10 cases). T1 weighted image of MRI showed low and medium signals and T2 weighted image showed medium and high signals(8 cases). There was no definite diagnosis before surgery. Ten patients were treated with surgery, and it was confirmed intraoperatively that the tumors were not adjacent to the optic nerve and orbital periosteum. The pathological diagnoses were mostly epithelial meningiomas (9 cases). There were no significant changes in visual acuity, but temporary eye movement disorders occurred postoperatively (10 cases). The patients were followed for 6 months to 6 years. Two cases underwent recurrent at 3 months and 2 years after operation, and received treatment of γ-knife radiation therapy. The tumor reduced after γ-knife radiotherapy, and had no change in 2 years and 6 years, respectively. Conclusions: As a kind of rare orbital tumors, it is difficult to diagnose orbital ectopic meningiomas accurately. The clinical features and imaging findings can help to detect the disease, but lacking the characteristics of optic nerve sheath meningiomas and periosteal meningiomas. Surgical resection could achieve a good prognosis without visual impairment. If the tumor recurs after pathological diagnosis, γ-knife conformal radiation therapy may still be effective for tumor recurrence. (Chin J Ophthalmol, 2018, 54: 665-670).

MiR-519d reduces the 5-fluorouracil resistance in colorectal cancer cells by down-regulating the expression of CCND1.

OBJECTIVE: To investigate the effects of miR-519d on the 5-fluorouracil resistance in colorectal cancer cells and to explore the mechanism. MATERIALS AND METHODS: Colorectal cancer cells HCT116 and SW480 were transfected with miR519d-mimic or siCCND1 by transient transfection. The sensitivity of cells to 5-Fu was assayed by MTT assay. Dual luciferase assay was used to examine the effect of CCND1 on the sensitivity of cells to 5-Fu mediated by miR-519d. RESULTS: MiR-519d was overexpressed in colorectal cancer cells after transient transfection with miR-519d mimics. Overexpression of miR-519d increased the sensitivity of colorectal cancer cells to 5-Fu. MiR-519d negatively regulated the expression of CCND1 via directly bound to CCND1 3`UTR. si-CCND1 could downregulate the CCND1 expression in colorectal cancer HCT116 and SW480 cells. si-CCND1 increased the sensitivity of colorectal cancer cells to 5-Fu. CONCLUSIONS: miR-519d inhibits the expression of CCND1 and then plays a role in alleviating 5-Fu resistance in colorectal cancer cells.

Cardiovascular disease in rheumatoid arthritis: medications and risk factors in China.

This study aims to assess the risk factors of cardiovascular disease (CVD) and to determine the association of traditional and biologic disease-modifying anti-rheumatic drugs (DMARDs) with risk for CVD in Chinese rheumatoid arthritis (RA) patients. A cross-sectional cohort of 2013 RA patients from 21 hospitals around China was established. Medical history of CVD was documented. The patients' social background, clinical manifestations, comorbidities, and medications were also collected. Of the 2013 patients, 256 had CVD with an incidence of 12.7%. Compared with non-CVD controls, RA patients with CVD had a significantly advanced age, long-standing median disease duration, more often male and more deformity joints. Patients with CVD also had higher rates of smoking, rheumatoid nodules, interstitial lung disease, and anemia. The prevalence of comorbidities, including hypothyroidism, diabetes mellitus (DM), hypertension, and hyperlipidemia, was also significant higher in the CVD group. In contrast, patients treated with methotrexate, hydroxychloroquine (HCQ), and TNF blockers had lower incidence of CVD. The multivariate analysis showed that the use of HCQ was a protective factor of CVD, while hypertension, hyperlipidemia, and interstitial lung disease were independent risk factors of CVD. Our study shows that the independent risk factors of CVD include hypertension, hyperlipidemia, and interstitial lung disease. HCQ reduces the risk of CVD in patients with RA.

[Clinical and pathological analysis of ocular tumors in 504 children cases].

Objective: To analyze the clinical features and pathological classification of chlidren's ocular tumors. Methods: Retrospective case series study. Five hundred and four cases (506 eyes) of ocular tumor with biopsy-proven in children below 14 years old between January 2002 and December 2014 from Tianjin Eye Hospital were performed to retrospectively investigated the lesion location, clinical features and histopathologic classification of these lesions. Results: Of 504 cases there were 246 boys (248 eyes) and 258 girls (258 eyes) patients. The mean age at diagnosis was 6.4 years, ranged from 4 months to 14 years. Of 328 cases (65.1%) of eyelid and ocular surface, 2 cases (0.6%) were malignant tumors and other tumors were all benign tumors. The leading four tumors were corneal dermoid, dermoid cysts, nevus and pilomatricoma. Of 123 cases (24.4%) of orbital tumors, 13 cases (10.6%) were malignant tumors and other tumors were all benign tumors. The leading four tumors were dermoid cysts, lymphangiomas, hemolymphangioma and venous hemangioma. Of 53 cases (10.5%) of intraocular tumors, 41 cases (77.4%) were malignant tumors which were all retinoblastoma. Conclusions: Most of children's ocular tumors were congenital and embryonic tumors. The most common ocular tumors of 504 children patients were from eyelid and ocular surface. Corneal dermoid and dermoid cysts were the most benign ones. Retinoblastoma and rhabdomyosarcoma were the most malignant ones.(Chin J Ophthalmol, 2016, 52: 764-768).

[Clinical and pathologic observation of uveal metastatic carcinoma].

Objective: To observe the clinical and pathological features of uveal metastatic carcinoma. Methods: It was a retrospective case series study. The clinical manifestation, growth pattern, tumor types and relative pathological features of 13 patients visiting from January 1980 to December 2014 with uveal metastatic carcinoma in Tianjin Eye Hospital were analyzed retrospectively. Results: There were 13 cases, 6 cases of male and 7 of female. Age was from 37.0 to 66.0 years old. The mean age was 52.1 years old. all cases were monocular. There were 5 cases with right eye and 8 cases with left eye. Among 13 cases, 10 tumors were in posterior choroid, one tumor was in anterior choroid and ciliary body, 2 tumors were in the iris. There were 5 patients with lung cancer, 4 patients with breast cancer, 1 patient with prostate cancer, 1 patient with thyroid cancer and 1 patient with esophageal cancer. The primary tumor wasn't found in 1 patient. The rapid decrease of visual acuity showed in 10 patients with posterior choroidal metastatic carcinoma, 8 of them accompanied with extensive retinal detachment and 6 of them had secondary glaucoma. The multiple gray-white nodule or pink cauliflower mass on the papillary margin of iris were showed respectively in 2 patients with iris metastatic carcinoma. The pathological examination found that posterior choroidal metastatic carcinoma mainly located in temporal or nasal side choroids in 10 cases, among them, local or diffuse flat choroidal masses showed in 6cases, extensive mass involving choroid and ciliary body showed in 1 case, large nodular or globular choroidal mass showed in 2 cases, choroidal mass surrounded the optic disc in 1 case, optic nerve invasion showed in 3 cases and extraocular or orbital invasion showed in 3 cases. The scleral and subconjunctival invasion showed in 1 case of anterior choroid and ciliary body metastatic carcinoma. Conclusions: Uveal metastatic carcinoma manifested various growth pattern, the rapid decrease of visual acuity, flat or nodular choroidal solid mass, secondary retinal detachment and glaucoma were common clinical features. Some cases might invade extraocular or orbital tissue. (Chin J Ophthalmol, 2016, 52: 769-774).