Objective:To investigate the role and molecular mechanism of sensory neuron-derived exosomes (nExo) in mediating intervertebral disc degeneration (IDD).Methods:A rat IDD model was constructed, with nExo injected into the intervertebral disc. After 4 weeks, the degenerative grades of operated discs were evaluated using histological staining, while the senescent phenotype of nucleus pulposus stem cells (NPSC) in the tissue was evaluated using immunofluorescence staining. For in vitro experiments, 24 hours after the treatment of nExo to NPSC, immunoblotting, flow cytometry, or senescence-associated β-galactosidase staining was applied to evaluate the senescent phenotype of NPSC. Transcriptomics analysis was applied to identify the key molecules that mediate nExo-induced cells senescence. After 4 weeks of injecting nExo and TXN into the rat tail disc degeneration model.Results:nExo increased the degenerative grades of IDD and increased the proportion of TEK +p16 + and TEK +p21 + cells (from 36.32% ±4.04%, 33.69% ±4.56% in IDD group to 56.41% ±5.26%, 50.14% ±8.49% in IDD+nExo group, respectively; t=7.420, P<0.001; t=4.184, P<0.0019, respectively) in the disc tissue. Besides, nExo promoted the expression of p16 and p21 in NPSC and increased the percentage of cells with positive senescence-associated β-galactosidase staining (from 7.32%±1.73% to 58.22%±11.38%, t=7.658, P=0.002), while the percentage of G2/M cells was downregulated (from 18.10%±1.32% to 1.60%±0.67%, t=19.290, P<0.001). Transcriptomic analysis showed that the differential genes of CTRL vs. nExo were closely related to cell senescence, and TXN was screened by intersecting the differential gene set with the cellular senescence gene sets from the published database. Furthermore, we verified that nExo decreased the content of TXN in NPSC, while exogenous TXN downregulated the expression of p16 and p21 in NPSC, reduced the positive cell rate of senescence-associated β-galactosidase staining (from 58.84%±3.99% to 21.68%±8.16%, t=7.048, P=0.021), increased the percentage of G2/M cells (from 1.21%±0.34% to 15.26%±2.60%, t=9.259, P=0.001). TXN significantly reduced the grade of disc tissue degeneration (histological score: 14.33±0.82 in the nExo group; 8.17±1.17 in the nExo+TXN group, t=10.590, P<0.001), significantly increased the content of extracellular matrix (from 10.94±4.35 μg/mg to 50.55±12.16 μg/mg, t=7.512, P<0.001), and reduced the proportion of TEK +p16 + and TEK +p21 + double-positive cells (from 54.92%±4.21% and 60.31%±9.02% to 27.93%±3.26% and 33.75%±8.07%, respectively; t=12.430, P<0.001; t=5.375, P<0.001, respectively). Conclusion:nExo promotes cell senescence and IDD by downregulating TXN in NPSC.

Objectives:To analyze the clinical features and prognosis of patients with medullary thyroid carcinoma combined with papillary thyroid carcinoma (combined carcinoma).Methods:The clinical data of 24 patients admitted to Tianjin Medical University Cancer Hospital from Nov 2012 to Dec 2019 were retrospectively analyzed. The treatment methods, pathological results, and prognosis of all patients were examined.Results:The results showed that combined carcinoma accounted for 10.0% (24/241) of all medullary thyroid carcinoma cases. In the combined cancer group, 45.8% (11/24) patients had lymph node metastasis, and the type of metastasis matched the largest lesion. There were no significant differences in gendex ratio ( χ2=0.164, P>0.05), age at onset ( t=1.381, P>0.05), maximum diameter of lesion ( Z=-1.733, P>0.05), multifocality ( χ2=2.695, P>0.05), and lymph node metastasis in the central ( χ2=1.625, P>0.05) and lateral neck regions ( χ2=1.537, P>0.05) between combined cancer patients and those with MTC alone. The median follow-up time for the 24 patients was 77.6 months. Local recurrence was observed in 2 cases, while no distant metastasis was found. There were no significant differences in disease-free survival, disease-specific survival, and overall survival between combined cancer and pure MTC groups (all P>0.05). Conclusion:The pathological characteristics and prognosis of medullary thyroid carcinoma combined with papillary thyroid carcinoma are similar to those of pure MTC. Therefore, clinical treatment decisions can be similar to pure MTC.

Objective:To investigate the etiology, clinical features and treatment of familial exudative vitreoretinopathy (FEVR) secondary glaucoma.Methods:A retrospective clinical study. From January 1, 2016 to January 1, 2022, 15 patients (17 eyes) were diagnosed with FEVR secondary glaucoma in Beijing Tongren Hospital, Capital Medical University were included in the study. All patients underwent systematic ophthalmological evaluation. According to the patient's age, visual acuity, intraocular pressure, anterior segment, vitreous body and retina condition, the choice of translimbal lensectomy combined with vitrectomy, goniectomy, cyclophotocoagulation, intravitreal injection of anti-vascular endothelial growth factor (VEGF) treatment were chosen. The follow-up time was 3 to 37 months. The clinical characteristics of the affected eye, and the changes of intraocular pressure, anterior chamber depth and complications after surgery were observed.Results:Among the 15 patients, there were 11 males with 13 eyes, and 4 females with 4 eyes. Age was 6.14±7.37 years old. FEVR stages 2B, 3B, 4A, 4B, 5A, and 5B were 1, 1, 5, 6, 3, and 1 eye, respectively. The intraocular pressure of the affected eye was 42.74±9.06 mm Hg (1 mm Hg=0.133 kPa). All eyes had shallow anterior chamber and angle closure, anterior or posterior iris adhesions, lens opacity, retinal detachment, iris neovascularization in 4 eyes, and vitreous hemorrhage in 2 eyes. Sixteen eyes were treated with translimbal lensectomy combined with vitrectomy and goniotomy, of which 8 eyes were treated with anti-VEGF treatment; 1 eye was treated with cyclophotocoagulation combined with anti-VEGF treatment. After operation, the intraocular pressure of 16 eyes returned to normal range, and the depth of anterior chamber of 16 eyes returned to normal, and no obvious complications occurred.Conclusions:The main etiology of secondary glaucoma in FEVR is the structural and functional abnormalities of the anterior chamber and angle, which are found in the 2B and above stages of FEVR. The lensectomy and vitrectomy via limbal approach can effectively control the intraocular pressure and restore the anterior chamber, with no serious complications.

Objective:To review the outcome of intravitreous anti-vascular endothelial growth factor (VEGF) treatment in patients with X-linked retinoschisis (XLRS) complicated with vitreous hemorrhage (VH).Methods:A retrospective clinical study. From March 1, 2016 to April 1, 2022, 18 patients (19 eyes) diagnosed with XLRS complicated with vitreous hemorrhage in Beijing Tongren Hospital, Capital Medical University of Eye Center were included. All the patients were male, with a median age of 7.05±3.8 years. Best corrected visual acuity (BCVA) and wide-angle fundus photography were performed in all the patients. BCVA was carried out using international standard visual acuity chart, and converted into logarithm of minimum resolution angle (logMAR) in statistics analysis. According to whether the patients received intravitreal injection of ranibizumab (IVR), the patients were divided into injection group and observation group, with 11 eyes in 10 cases and 8 eyes in 8 cases, respectively. In the injection group, 0.025 ml of 10 mg/ml ranibizumab (including 0.25 mg of ranibizumab) was injected into the vitreous cavity of the affected eye. Follow-up time after treatment was 24.82±20.77 months. The VH absorption time, visual acuity changes and complications were observed in the injection group after treatment. Paired sample t test was used to compare BCVA before and after VH and IVR treatment. Independent sample t test was used to compare the VH absorption time between the injection group and the observation group. Results:LogMAR BCVA before and after VH were 0.73±0.32 and 1.80±0.77, respectively. BCVA decreased significantly after VH ( t=-3.620, P=0.006). LogMAR BCVA after VH and IVR were 1.87±0.55 and 0.62±0.29, respectively. BCVA was significantly improved after IVR treatment ( t=6.684, P<0.001). BCVA records were available in 5 eyes before and after IVR, and the BCVA values after VH and IVR were 0.58±0.31 and 0.48±0.20, respectively, with no statistically significant difference ( t=1.000, P=0.374). BCVA increased in 1 eye and remained unchanged in 4 eyes after treatment. BCVA records were available in 5 eyes before VH and after VH absorption in the 8 eyes of the observation group. LogMAR BCVA before VH and after VH absorption were 0.88±0.28 and 0.90±0.26, respectively, with no significant difference ( t=-1.000, P=0.374). After VH absorption, BCVA remained unchanged in 4 eyes and decreased in 1 eye. The absorption time of VH in the injection group and the observation group were 1.80±1.06 and 7.25±5.04 months, respectively. The absorption time of VH was significantly shorter in the injection group than in the observation group, the difference was statistically significant ( t=-3.005, P=0.018). Multivariate linear regression analysis showed that IVR treatment was significantly correlated with VH absorption time ( B=-6.66, 95% confidence interval -10.93--2.39, t=-3.40, P=0.005). In the injection group, VH recurrence occurred in 1 eye after IVR treatment. Vitrectomy (PPV) was performed in one eye. In the 8 eyes of the observation group, VH recurrence occurred in 2 eyes, subsequent PPV in 1 eye. The rate of VH recurrence and PPV was lower in the injection group, however, the difference was not statistically significant( P=0.576, 1.000). In terms of complications, minor subconjunctival hemorrhage occurred in 2 eyes and minor corneal epithelial injury occurred in 1 eye in the injection group, and all recovered spontaneously within a short time. In the injection group, 9 eyes had wide-angle fundus photography before and after IVR treatment. There was no significant change in the range of peripheral retinoschisis after treatment. No obvious proliferative vitreoretinopathy, infectious endophthalmitis, retinal detachment, macular hole, complicated cataract, secondary glaucoma or other serious complications were found in all the treated eyes, and there were no systemic complications. Conclusion:Intravitreous anti-VEGF treatment may accelerate the absorption of vitreous hemorrhage in patients with XLRS. No impact is found regarding to the peripheral retinoschisis.

Objective:To investigate the efficacy of 532 nm wavelength laser using indirect ophthalmoscope combined with ranibizumab (IVR) in treating stage 2 and greater pediatric Coats disease.Methods:A retrospective, non-controlled clinical study. From February 2018 to August 2020, 21 eyes of 21 patients with Coats disease stage 2 and greater diagnosed by examination in the Eye Center of Beijing Tongren Hospital were included in the study. Among them, 20 patients were males; 1 patient was female. Mean age was 5.00±1.92 years old. Stage 2A, 2B, 3A, 3B, and 4 were 2, 8, 7, 2, and 2 eyes, respectively. All eyes underwent wide-field fundus color photography and fluorescein fundus angiography (FFA). Best corrected visual acuity (BCVA) was performed in 17 eyes. Abnormal dilated retinal blood vessels, interretinal and subretinal exudates were found in all eyes. Abnormally dilated capillaries and aneurysms in the retina was shown in FFA examination. All eyes underwent 532 nm laser photocoagulation using indirect ophthalmoscope combined with IVR. Patients with severe retinal detachment of stage 3B or greater were treated by external drainage of subretinal fluid (SRF). The subsequent treatment was the same as before. The follow-up time was 35.67±6.13 months. Relevant examinations were performed using the same equipment and methods before. The frequency of treatment, visual acuity changes, anatomic prognosis, and complications were observed.Results:The frequency of eye photocoagulation was 2.43±0.98. The number of IVR treatments was 2.00±0.89. Three eyes were treated with SRF drainage in the first time. At the last follow-up, visual acuity improved, no change, and decreased in 5, 11, and 1 eyes after BCVA examination, respectively. In 21 eyes, the retina was in situ in 17 eyes; 5 eyes with retinal cysts. During the follow-up, cataract and vitreous hyperplasia occurred in 1 eye, which was treated by vitrectomy, and mild vitreous hyperplasia occurred in 1 eye.Conclusion:Indirect ophthalmoscope 532 nm wavelength laser combined with IVR is an effective treatment for pediatric Coats disease.

Objective:To study the long-term effects and outcomes of adjuvant intravitreal injection of conbercept (IVC) therapy in juvenile Coats disease.Methods:A retrospective case series study. From January 1, 2015 to December 31, 2018, 40 patients (40 eyes) who were diagnosed as juvenile Coats disease at Beijing Tongren Hospital Affiliated to Capital Medical University were included in the study. Among them, there were 37 males (37 eyes) and 3 females (3 eyes). All patients had unilateral Coats disease. The average age was 55.00 (44.75, 81.25) months. Five eyes were in stage 2B, 15 eyes were in stage 3A, 19 eyes were in stage 3B and 1 eye was in stage 4. Idiopathic retinal vascular telangiectasia associated with extensive subretinal fluid (SRF) (stage 3 or above) or massive foveal exudation and edema (stage 2B) were found in fundus examination. All affected eyes underwent wide-field color fundus images and fluorescein fundus angiography. Thirty-one eyes underwent best corrected visual acuity (BCVA) examination. The BCVA was carried out using a standard logarithmic visual acuity chart, which was converted into the logarithmic minimum angle of resolution (logMAR) visual acuity. All cases received adjuvant IVC combined with treatments such as retinal photocoagulation. The average number of injections was 4 (1, 5). The average follow-up after initial treatment was 59.00 (52.50, 63.00) months. The changes in BCVA, occlusion of abnormal blood vessels in fundus, absorption of SRF and ocular and systemic complications were observed.Results:At last follow-up, among 31 affected eyes with the examination of BCVA, 13 (32.5%, 13/40) eyes had an improved vision, 12 eyes(30.0%, 12/40) had a stable vision and 6 eyes (15.0%, 6/40) had a decreased vision. The difference between average logMAR BCVA of the affected eyes in each stage after treatment and that before treatment was not statistically significant ( Z=-0.56, -1.80, -0.84; P>0.05). Abnormal blood vessels in fundus were all partially or completely occluded, and SRF was obviously or completely absorbed in all cases; of which, 28 eyes (70.0%, 28/40) were completely occluded, and 12 eyes (30.0%, 12/40) were partially occluded. No patient underwent eye enucleation. Nineteen eyes (47.5%, 19/40) developed vitreoretinal fibrosis; 8 eyes (20.0%, 8/40) developed tractional retinal detachment; 15 eyes (37.5%, 15/40) developed complicated cataract. None had ocular or systemic complications related to IVC therapy during follow-up. Conclusions:IVC combined with classic treatments such as photocoagulation in juvenile Coats disease can keep or improve the visual acuity in most juvenile patients by reducing SRF. IVC is a long-term safe and effective adjuvant therapy in juvenile Coats disease.

Objective:To observe the efficacy of parsplana vitrectomy (PPV) combined with 0.7 mg dexamethasone sustained-release Ozurdex intravitreal implantation in the treatment of children with ocular toxocariasis (OT).Methods:A retrospective clinical study. Fifty-three pediatric patients (53 eyes) diagnosed with OT and underwent PPV in Beijing Tongren Eye Center of Beijing Tongren hospital from March 2015 to December 2021 were included. There were 30 males and 23 females, with an average age of 7.07±3.45 (4-14) years; all were unilateral. Color Doppler imaging, fundus color photography, optical coherence tomography examinations were performed for patients who can cooperated with the examiners. Forty-three eyes were examined by best corrected visual acuity (BCVA); 47 eyes were examined by intraocular pressure; 29 eyes were examined by ultrasound biomicroscopy. According to the location of granuloma, OT was divided into posterior pole granulomatous type (posterior type), peripheral granulomatous type (peripheral type), and chronic endophthalmitis type. According to whether Ozurdex was implanted into the vitreous cavity after PPV, the children were divided into the oral glucocorticoid group after PPV (group A) and the PPV combined with vitreous cavity implantation of Ozurdex group (group B), 37 cases with 37 eyes and 16 cases with 16 eyes, respectively. There was no significant difference in age ( t=0.432), sex composition ratio ( χ2=0.117), BCVA ( χ2=0.239), and clinical type ( χ2=0.312) between the two groups ( P>0.05). The follow-up time after surgery was ≥5 months. The intraocular pressure at 1 week and 1, 3, and 6 months after surgery, the changes of BCVA and the occurrence of complications such as concurrent cataract and epimacular membrane were observed at the last follow-up, and the incidence of obesity in the children during the follow-up period was recorded. The measurement data between groups was compared by independent sample t test; the enumeration data was compared by χ2 test. Results:One month after the operation, the intraocular pressure of group A and group B were 15.17±6.21 and 25.28±10.38 mm Hg (1 mm Hg=0.133 kPa) respectively; the intraocular pressure of group B was significantly higher than that of group A, the difference was statistically significant ( t=0.141, P=0.043). At the last follow-up, there was no significant difference in the percentage of visual acuity improvement between the two groups ( χ2=0.315, P=0.053); there was no significant difference in the incidence of concurrent cataract and epimacular membrane ( χ2=0.621, P >0.05). Among the 37 cases in group A, 32 cases (86.5%, 32/37) developed obesity symptoms during the follow-up period. Conclusion:PPV combined with intravitreal implantation of Ozurdex and oral glucocorticoid after PPV can effectively improve the visual acuity of the affected eye; the incidence of complications is similar, however, the incidence of obesity after oral glucocorticoid is higher.

Objective:To investigate the difference of clinicopathological characteristics between mixed medullary and papillary carcinoma of thyroid and medullary carcinoma coexistent with papillary carcinoma.Method:The clinicopathological data of 3 MMPTC cases and 9 MTC-PTC cases treated at Tianjin Medical University Cancer Institute & Hospital during the past ten years were retrospectively analyzed. The differences in clinical characteristics, pathological characteristics, immunohistochemistry results, treatment and prognosis of the two groups were compared.Results:In the MMPTC group, the median onset-age was 59 years old. 3 patients were all medullary carcinoma colliding with micropapillary carcinoma. The immunohistochemistry results showed that medullary carcinoma and papillary carcinoma showed their distinctive immunohistochemical characteristics. The lymph node metastasis rate was 66.7% (2/3). In MTC-PTC group, the median onset-age was 55; 8 out of 9 patients had an increased preoperative calcitonin level. Medullary carcinoma and papillary carcinoma showed their distinctive immunohistochemical characteristics. Four out of the 9 cases had lymph node metastasis.Conclusion:Compared with MTC-PTC, MMPTC is more common in middle-aged and elder patients, with higher lymph node metastasis rate. The pathogenesis of MTC-PTC is similar to papillary thyroid carcinoma, and the treatment should be individualized. The prognosis of these two groups of patients is fair.

Objective:To investigate the BRAF(V600E)gene mutation of pediatric papillary thyroid carcinoma (PTC) and refine their clinicopathological correlates. Methods:Tumor tissue samples of pediatric PTCs (≤18 years old) were collected from tumor tissue bank of Tianjin Medical University Cancer Institute and Hospital from January 2012 to December 2016.The medical records of 22 patients with pediatric PTC were reviewed retrospectively.The frequencies of BRAF(V600E) mutation were evaluated and the correlation between BRAF(V600E) mutation and clinical characteristics were analyzed. Results:BRAF(V600E) mutations were present in 45.5% of cases (10 cases). BRAF(V600E) mutation in pediatric PTC was obviously lower than that in adults PTC(77.7%) ( χ2=11.250, P=0.001). BRAF(V600E) mutation in>12-year-old group (66.7%) was remarkably higher than that in ≤12-year-old group (20.0%) ( P<0.05). BRAF(V600E) mutation in female (69.2%) was greatly higher than that in male (11.1%) ( P<0.05). There was no significant correlation with BRAF(V600E) mutation and multiple tumor, tumor size, highly invasive subtype, extrathyroidal extension, lymph node metastasis and radiological history of infants (all P>0.05). The median follow-up time was 45 months.No patients died and BRAF(V600E) mutation was not associated with the increase of recurrence rate ( P>0.05). Conclusions:BRAF(V600E)gene mutation in pediatric PTC is lower than that in adults. BRAF(V600E) mutation does not portend a more aggressive clinical biological behavior in pediatric PTC.

Background/Aims: There is less acid burden in Chinese gastroesophageal reflux disease (GERD) patients. However, the Lyon consensus proposed a higher threshold of acid exposure time (AET > 6%) for GERD. The aims are to apply the updated criteria in Chinese GERD patients and clarify its influence on clinical outcome. Methods: Patients who were referred for both esophageal high-resolution manometry and 24-hour esophageal pH monitoring due to reflux symptoms were retrospectively screened. Those patients with AET > 4% was included and grouped into either AET 4-6% or AET > 6%. Their manometric profile, reflux profile, and response to proton pump inhibitors (PPIs) were evaluated. Adjunctive evidence proposed in the Lyon consensus was added in patients with AET 4-6% for therapeutic gain. Another group of patients (n = 144) with AET < 4% were included as non-GERD patients. Results: In total, 151 patients (102 males) were included with 113 patients AET > 6% (74.9%). GERD patients with AET > 4% were with more male, older patients, and higher body mass index compared with non-GERD patients. Meanwhile, GERD patients were less competent in esophagogastric junction pressure. However, the manometric and reflux profile were similar between patients with AET > 6% and 4-6%. The response rate of PPI therapy was 64.6% and 63.2%, respectively, in groups of AET > 6% and 4-6% (P > 0.05). When adjunctive evidence was added in patients with AET 4-6%, no therapeutic gain was obtained. Conclusions The efficacy of PPI therapy was similar in patients with AET > 6% and 4-6%. The increase of the AET threshold did not influence the clinical outcome of Chinese GERD patients.