Exosomes are nanoscale extracellular vesicles that are secreted by a variety of cells in the body. They carry particular miRNA, protein molecules, transcription factors, and other information molecules, and they play a role in the pathophysiological regulation of a number of diseases in the body. Exosomes can persist steadily in biological tissues and bodily fluids. Exosomes have quickly advanced in ophthalmology in recent years due to the extensive studies of exosomes in a variety of fields, such as diabetic retinopathy, age-related macular degeneration, autoimmune uveitis, corneal disease, glaucoma, and other diseases. The number of people who are blind caused by diabetic retinopathy is rising as living standards rise. However, it is still unclear how diabetic retinopathy works. In recent years, many studies have found that exosomes play an important role in diabetic retinopathy. In this paper, the most recent developments in exosome studies as they relate to the pathogenesis and progression of diabetic retinopathy are reviewed.

Background: The accessory tendon of the extensor hallucis longus (ATEHL) muscle is a common abnormal structure, and its clinical significance remains debatable. In this study, we provide the incidence of the ATEHL and characterize its morphological types in Asian cadavers and investigate its clinical applications. Methods: The tendons from 50 adult cadaveric feet, fixed in 10% formalin, were analyzed. We measured the length and width of both the ATEHL and the extensor hallucis brevis (EHB). Results: All dissected specimens had an ATEHL. The first metatarsophalangeal joint was surrounded by an accessory tendon that inserted onto the joint capsule and the dorsal base of the proximal phalanx. We classified the ATEHL into 3 types based on their directions. Differences in ATEHL type based on sex were not statistically significant. Conclusions We found an ATEHL in all cadaveric specimens in this study. We surmise that the ATEHL acts as an antagonist with the EHB when the toe is extending, which might help prevent the occurrence of hallux valgus deformity.

Background: The accessory tendon of the extensor hallucis longus (ATEHL) muscle is a common abnormal structure, and its clinical significance remains debatable. In this study, we provide the incidence of the ATEHL and characterize its morphological types in Asian cadavers and investigate its clinical applications. Methods: The tendons from 50 adult cadaveric feet, fixed in 10% formalin, were analyzed. We measured the length and width of both the ATEHL and the extensor hallucis brevis (EHB). Results: All dissected specimens had an ATEHL. The first metatarsophalangeal joint was surrounded by an accessory tendon that inserted onto the joint capsule and the dorsal base of the proximal phalanx. We classified the ATEHL into 3 types based on their directions. Differences in ATEHL type based on sex were not statistically significant. Conclusions We found an ATEHL in all cadaveric specimens in this study. We surmise that the ATEHL acts as an antagonist with the EHB when the toe is extending, which might help prevent the occurrence of hallux valgus deformity.

Oocyte cryopreservation is widely used for clinical and social reasons. Previous studies have demonstrated that conventional slow-freezing cryopreservation procedures, but not storage time, can alter the gene expression profiles of frozen oocytes. Whether vitrification procedures and the related frozen storage durations have any effects on the transcriptomes of human metaphase II oocytes remain unknown. Four women (30-32 years old) who had undergone IVF treatment were recruited for this study. RNA-Seq profiles of 3 fresh oocytes and 13 surviving vitrified-thawed oocytes (3, 3, 4, and 3 oocytes were cryostored for 1,2, 3, and 12 months) were analyzed at a single-cell resolution. A total of 1987 genes were differentially expressed in the 13 vitrified-thawed oocytes. However, no differentially expressed genes were found between any two groups among the 1-, 2-, 3-, and 12-month storage groups. Further analysis revealed that the aberrant genes in the vitrified oocytes were closely related to oogenesis and development. Our findings indicated that the effects of vitrification on the transcriptomes of mature human oocytes are induced by the procedure itself, suggesting that long-term cryostorage of human oocytes is safe.
Adult ; Cryopreservation ; Female ; Humans ; Metaphase ; Oocytes ; RNA-Seq ; Vitrification

ObjectiveTo assess the diagnostic performance of deep learning elastography （DLE） for liver fibrosis. MethodsTotally 545 chronic liver disease patients with liver biopsy were retrospectively enrolled. The results of DLE， two dimensional shear wave elastography （2D-SWE）， serological markers and transient elastography （TE） were collected. Area under receiver operating curve （AUC） was calculated and inter-compared while evaluating liver fibrosis. Then we tested the diagnostic performance of the trained DLE model in different validation groups when evaluating the same liver fibrosis stage， respectively， to assess the stability of DLE. ResultsDLE showed statistically significantly （P＜0.05） better results than any other methods. When evaluating F=4， F≥3 and F≥2， the AUC of DLE was 0.99， 0.98 and 0.92， respectively. 2D-SWE showed a second high diagnostic performance， while the AUCs were 0.89， 0.86 and 0.86， respectively. Little difference in diagnostic performance was showed among other methods， while the highest AUC was no more than 0.81. Besides， no statistical difference was showed among the three validation groups， while accessing the same liver fibrosis stage. ConclusionsDLE can be used to accurately assess liver fibrosis， whose diagnostic performance is higher than that of 2D-SWE， serological markers and TE. Moreover， with good stability， DLE is expected to become a new method for noninvasive assessment of liver fibrosis.

OBJECTIVETo compare the expression of pinopodes, the marker of endometrial receptivity, during the implantation window in Kunming mice stimulated with two different doses of raloxifene (RAL).

METHODSForty-eight 8-week-old female Kunming mice were randomly divided into 4 groups (n=12), namely saline group, clomiphene citrate (CC, 18 mg/kg) group, RAL (33 mg/kg) group and RAL (44 mg/kg group). In each group, the mice received intragastric administration of 1 mL of normal saline containing CC or RAL at the specified doses or saline only as indicated for ovulation induction, once daily for 2 days. The mice received then injection with 5 IU human chorionic gonadotropin (HCG) and mated and on day 4.5 of gestation, the pregnant mice were sacrificed for examination of the uterus with scanning electron microscopy.

RESULTSAbundant and well developed pinopodes were observed in the endometrium of the mice in the 2 RAL groups and in the saline control group. The mice in CC group showed obviously reduced endometrial pinopodes with poor development.

CONCLUSIONSRAL at two different doses does not obviously affect the expression of pinopodes in the uterine epithelium of mice, suggesting the safety of RAL at these two doses for ovulation induction without causing adverse effects on endometrial receptivity.

PURPOSE: In this study, we aimed to evaluate lymphocyte-activation gene-3 (LAG-3) expression and its prognostic value in neoadjuvant-treated triple-negative breast cancer (TNBC). METHODS: LAG-3, programmed death-1 (PD-1), programmed death ligand-1 (PD-L1), and CD8⁺ tumor-infiltrating lymphocyte (TILs) levels were examined using immunohistochemistry in 148 preand 114 post-neoadjuvant chemotherapy (NACT) specimens of human TNBC tissue. Correlations between expression levels and clinicopathological features were analyzed. Prognostic values for combined detection in TNBC following NACT were evaluated. RESULTS: In pre-NACT specimens, LAG-3 expression showed a significant association with pathological complete response (pCR, p=0.038) and was correlated with PD-1 (p<0.001) and PD-L1 (p=0.008). In post-NACT specimens, high expression of LAG-3 showed significant effects on nodal status (p=0.023) and PD-1 (p<0.001). The expression of immune markers on TILs significantly increased following NACT. Multivariate analysis indicated that only nodal status (odds ratio [OR], 0.226; 95% confidence interval [CI], 0.079–0.644; p=0.005) and high quantities of CD8⁺TILs (OR, 3.186; 95% CI, 1.314–7.721; p=0.010) are independent predictors of pCR. Nodal status (hazard ratio [HR], 2.666; 95% CI, 1.271–5.594; p=0.010), CD8⁺TILs (HR, 0.313; 95% CI, 0.139–0.705; p=0.005), and the LAG-3-high/PD-L1-high group (HR, 2.829; 95% CI, 1.050–7.623; p=0.040) provided prognostic values for patients with TNBC following NACT. CONCLUSION: CD8+TILs were sensitive predictive markers in response to NACT. High expression of LAG-3 in residual tissues, especially in combination with PD-L1, was associated with poor prognosis.
Biomarkers ; Drug Therapy ; Humans ; Immunohistochemistry ; Lymphocytes, Tumor-Infiltrating ; Multivariate Analysis ; Neoadjuvant Therapy ; Polymerase Chain Reaction ; Prognosis ; Triple Negative Breast Neoplasms*

OBJECTIVETo compare the expression of DKKL1 in ejaculated spermatozoa of normal fertile men and men with asthenospermia and investigate the role of DKKL1 in the pathogenesis of asthenospermia.

METHODSThe characteristics of semen samples collected from normal fertile men and men with asthenospermia were analyzed using computer-assisted sperm analysis according to WHO criteria. The ejaculated sperms were isolated by Percoll discontinuous density gradients to detect the expression of DKKL1 mRNA and protein using real-time PCR and Western blotting.

RESULTSThe expression of DKKL1 mRNA was significantly down-regulated by 11.1 times in asthenospermic men as compared with that in normal fertile men (P<0.01). Western blotting showed that the expression of DKKL1 protein was down-regulated by 2.4 times in asthenospermic men compared to normal fertile men.

CONCLUSIONThe expression of DKKL1, which may play an important role in sperm motility,is significantly decreased in ejaculated spermatozoa of men with asthenospermia.

The process of intervertebral disc degeneration,which could result in intervertebral disc structural and functional change,is a chronic one with multiple factors.The pathophysiologic process is still not completely find out.More and more research reports manifest that certain gene polymorphism also lead to increased risk of intervertebral disc degeneration except environmental factors.Discussions about related genetic factors and their pathophysiological role in the process of degeneration could have a further understanding to disease development.Elucidating genetic components which are associated with degeneration could not only provide insights into the mechanism of the process,but also have clinical significance for early diagnosis and prevention.In order to have a thorough understanding of functional role played by different genes,this paper summarize polymorphism and disease correlation by selecting 15 genes after reviewed the related literature published in recent years.Genetic polymorphisms in 15 genes have been analyzed in association with intervertebral disc degeneration,including aggrecan,collagen Types Ⅰ,Ⅸ and Ⅺ,fibronectin,HAPLN 1,CILP,MMP-1,2 and 3,PARK2,IL-1,6 and VDR.Each genetic polymorphism codes for a protein which has a functional role in the pathogenesis of disease.Among the 15 genes analyzed,polymorphisms in aggrecan,Type Ⅸ collagen,MMP3,IL1,IL6 and VDR show the most promise as functional variants.Genetic studies are necessary for understanding the mechanism of the degeneration.Relevant genetic information could be used as a predictive model for determining individuals' risk for intervertebral disc degeneration eventually.

Objective To investigate the effect of cystatin C (Cys C) on adventitia in rabbit abdominal aorta restenosis after angioplasty and its mechanism.Methods 48 New Zealand white rabbits were randomly divided into injury group (receiving balloon dilation of abdominal aorta),the treatment group (taking Cys C monoclonal antibody therapy) and the control group (receiving femoral artery puncture and catheter sheath without balloon dilation and intervention of Cys C monoclonal antibody injection),and each group had 16 rabbits.Peripheral vein blood was drawn to measure the serum level of cystatin C before and 8 h,1 day,1 week,3 weeks,6 weeks after the operation in all rabbits.After 6 weeks of operation,the abdominal aorta were taken and stained with HE.Vascular morphometry analysis and adventitial cell count were conducted.Smooth muscle actin (SM-actin) and proliferating cell nuclear antigen (PCNA) expressions in the adventitia were observed by immunohistochemical staining.The number of PCNA positive cell in the adventitia was counted and the PCNA proliferation index was calculated.The vascular remodeling index,vascular external elastic lamina area (EELA),internal elastic lamina area (IEIA) were used to evaluate the vascular remodeling and the residual stenosis and vascular cavity area was used to measure the vascular stenosis.Results Plasma Cys C level began to rise at 8h after operation and reached the peak at 1 week after operation,and continuously increased for 5 weeks in injury group,and reached to respectively at 3 weeks and 6 weeks after operation.The Cys C levels were significantly higher in injury group than in the treatment and control groups at different time points (all P＜0.05).There were no significant differences in Cys C levels at different time points between the treatment group and the control group.The injury group showed that the number of PCNA positive cells was higher in injury group than in treatment and control groups,both P＜0.05).Compared with the control group,the vascular luminal area,EELA and IELA were significantly increased (all P＜0.05).After treated with the monoclonal antibody Cys C intervention,the treatment group showed that lumen area,vascular EELA,IELA was significantly decreased (P＜0.05),and the vascular remodeling index and residual stenosis rate were decreased as compared with the injury group (0.871 vs.0.784,33.1％ vs.19.7 ％,both P＜0.05).Correlation analysis showed that Cystatin C level was positively correlated with the vascular lumen area,neointimal area,internal elastic lamina area,external elastic lamina area and the number of PCNA positive cells (r=0.812,0.797,0.876,0.932 and 0.822 respectively,all P＜0.01).Conclusions Plasma Cys C level is increased in rabbit after abdominal aorta balloon injury and has a positive correlation with the severity of arterial stenosis.High Cys C level can induce adventitial fibroblast activation,proliferation,phenotype transformation and migration,and accelerate the processes of atherosclerosis and stenosis.Cys C level is the independent risk factor for abdominal aortic stenosis.