The retinal neurons can not repair or regenerate once they are injured.Repairing the injured neurons by stem cell therapy is a hotspot in current study field.Endogenous stem cells exist in retina,which have the potential to restore retinal neural cells.Stimulating the endogenous retinal stem cells and using them to repair the injured retina has important research value and broad application prospects.It draws attention from neurobiology and ophthalmology researchers all over the world.The retinal regeneration ability of fish and amphibians is strong,while it is quite limited in birds and mammals.The retina regrowth character varies in different species.Ciliary marginal zone,retinal pigmented epithelial cells,and Müller cells are all potential cell sources for retinal regeneration.In fish,birds and mammals,the regenerated retinal neurons derived from Müller cells,while in amphibians they derived from RPE cells.The endogenous retinal stem cells need to be activated before they generated into retinal neurons.Researchers reported several methods to activate those cells,including using excitatory amino acid,growth factor,transcription factor,and intracellular signals.Here we reviewed the recent advances about retinal regeneration in different species including fish,amphibians,birds,and mammals;also the different source of endogenous retinal stem cells,including ciliary marginal zone,retinal pigmented epithelial cell,and Müller cell.Also,we reviewed the activation factors which could activate the endogenous retinal stem cells to proliferate and differentiate.

Objective To investigate the thyroid ultrastructural pathological changes of diabetes mellitus (DM) rats as well as the intervention effects of insulin and aminoguanidine. Methods Totally 87 rats were treated with streptozotocin to establish DM animal models and divided into DM group(n=27),insulin intervention group(n=32) and aminoguanidine intervention group(n=28),25 rats were taken as normal controls. Twelve and 20 weeks after the animal model establishment, animals were sacrificed, thyroid tissue was taken and ultrastructure was observed. Results In the thyroid of DM rats, follicular epithelial cells present as applanate shape, microvilli were depleted, rough endoplasmic reticulum dilated to irregular vesicular. None pinocytotic vacuole and casual primary or secondary lysosome were seen. Follicular cavity was dilated, colloid in the cavity had higher electronic-density. Interstitial edema, capillary base lamian was thickened at different stage. Proteo-substance deposition with granulo-shape, cloud shape or homogeneity appeared. The number of thyroid parafollicular cells increased. But endocrine granule in parafollicular cells was few. When compared with DM group, the thyroid tissue injury of insulin intervention group and aminoguanidine intervention group were lessened to different degree. Conclusion The hypofunctional thyroid follicular cells, large quantity of proteo-substance deposition in the interstitium and increased parafollicular cells of DM rats may be related with hyperglycemia toxicity. Insulin and aminoguanidine treatment have some protection effects.

Noninfectious uveitis refers to a category of inflammatory diseases involving the uvea,vitreous,optic disk and retina,with the exception of infectious factors or masquerade syndrome.These kind of blinding diseases are frequently recurrent,and the diagnosis and follow-up require fundus imaging techniques.OCT angiography (OCTA) is a rapid,noninvasive and quantifiable blood flow imaging modality that provides a depiction of the microvasculature morphology of the retinal and choroidal through different segmentation and detects the abnormal blood perfusion as well as the neovascularization.OCTA plays an important role in the diagnosis,assessment and follow-up for anterior uveitis,posterior uveitis and pan-uveitis such as Vogt-Koyanagi-Harada disease,Beh(c)et's disease,ocular sarcoidosis,birdshot chorioretinopathy,serpiginous choroiditis,multifocal choroiditis,punctate inner choroidopathy,acute zonal occult outer retinopathy,acute posterior multifocal placoid pigment epitheliopathy,multiple evanescent white dot syndrome,and also provides clue about their pathophysiologic mechanisms.

Noninfectious uveitis refers to a category of inflammatory diseases involving the uvea, with the exception of infectious factors or masquerade syndrome. The diagnosis and follow-up of noninfectious uveitis that involving retina or choroid require fundus imaging techniques. Fundus autofluorescence is a noninvasive imaging technique. Compared with fundus colorized photography, fundus fluorescein angiography and indocyanine green angiography, fundus autofluorescence indicates the functional status of retinal pigment epithelium and photoreceptor cells in a better way, thus playing a role in the pathophysiological mechanisms investigating, early diagnosis, disease progression monitoring and prognosis estimating of noninfectious uveitis, such as Vogt-Koyanagi-Harada disease, Beh?et disease, multifocal choroiditis, punctate inner choroidopathy, birdshot chorioretinopathy, multiple evanescent white dot syndrome, acute zonal occult outer retinopathy, acute posterior multifocal placoid pigment epitheliopathy and serpiginous choroiditis.

ObjectiveTo investigate the clinical guiding significance of Guideline for diagnosis and treatment of herb-induced liver injury in the diagnosis of herb-induced liver injury (HILI). MethodsA retrospective analysis was performed for the clinical data of 595 hospitalized patients who were admitted to 302 Hospital of PLA from January 2009 to January 2014 and diagnosed with HILI according to HILI diagnostic strategies recommended by American College of Gastroenterology. The chi-square test was used for comparison of categorical data between groups. ResultsAccording to the Guideline for diagnosis and treatment of HILI, all 595 patients (100%) were diagnosed with suspected HILI, 234 (39.3%) were diagnosed with clinical HILI, and 52(8.7%) were diagnosed with definite HILI. Among the patients with clinical and definite HILI, 85.0% and 94.2%, respectively, had a clinical type of cell injury, and 52.6% and 423%, respectively, had a severe disease. There were no significant differences in prognosis between the patients with suspected, clinical, and definite HILI, and 81.5%, 82.5%, and 80.8%, respectively, were cured. ConclusionGuideline for diagnosis and treatment of HILI can effectively guide the diagnosis of HILI, avoid misdiagnosis in clinical practice, and guarantee the safe application of Chinese herbal medicine. Its clinical guiding significance in the diagnosis of HILI awaits more prospective studies.

COVID-19 associated fundus lesions are mostly vascular occlusion or inflammatory changes. The affected vessels include both retinal macrovessels and microvessels, and the inflammatory changes are mainly autoimmune lesions. Clinically, the different lesions present as various fundus diseases, with varying degrees of impact on visual function. The mechanism of these lesions is considered to be related to direct injury of SARS-CoV-2, abnormal coagulation or inflammatory response caused by SARS-CoV-2. Awareness of fundus lesions associated to COVID-19 is helpful to figure out the pathophysiological mechanism of COVID-19 and promote in-depth studies for a deeper and complete understanding of the occurrence and full impact of COVID-19, emphasizing the importance of early prevention and control of the disease, and highlighting the significance of early intervention of the fundus diseases caused by COVID-19.

Objective To observe the features of temporal macular thinning and its value for the diagnosis of Alport syndrome (AS) in young patients.Methods Eighty-one young patients with AS (81 eyes) from Peking University First Hospital during January 2016 and July 2017 were included in this study.There were 67 males (67 eyes) and 14 females (14 eyes),the aged from 3 to 17 years,with the mean age of 9.6 years.Among 81 patients (81 eyes),there were 64 patients with X-linked AS (XLAS,including 53 males and 11 females),17 patients with autosomal recessive AS (ARAS,including 14 males and 3 females).One hundred healthy subjects aged 4 to 17 years were included as controls.Clinical data were retrospectively evaluated,including visual acuity,slit-lamp microscopy,dilated fundus photography,and OCT.Retinal thickness was measured with an OCT scan and the temporal thinning index (TTI) was calculated as stated in a previous study.The TTI values of each group was compared by One-way ANOVA or independent sample t test.The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic effectiveness for AS.Results The TTI of the control group,XLAS and ARAS patients were 6.46 ± 1.58,10.93 ± 3.77,12.14± 4.05,respectively.Compared with the control group,the TTI value of males were larger in the XLAS and ARAS group (F=45.056,P＜0.001),the TTI value of females were larger in the ARAS group (F=26.541,P＜0.001).The difference of TTI value in females was significant between the XLAS and ARAS groups (F=26.541,P＜0.001).In males,the area under the ROC curve was 0.896 (95％CI 0.837-0.955,P＜0.001).The optimal cutoff value of the TTI was determined as 9.47,with a sensitivity of 73.1％ and a specificity of 100％.Conclusions TTI is a common ocular finding in young patients with AS.In males,a TTI ＞ 9.47 may differentiate AS from normal males.

Objective To analyze the preventive and therapeutic effects of a traditional Chinese medicine Taohe Chengqi decoction on a rat models of hepatic encephalopathy ( HE) induced by thioacetamide ( TAA) .Methods The rat model of HE was established by intraperitoneal injection of TAA,and the effects of Taohe Chengqi decoction were observed by neurobehavioral changes,neurological test,blood ammonia,serum biochemical indexes,and liver and brain pathological examination.Results The rat model of hepatic encephalopathy was successfully established.Low, medium and high dose Taohe Chengqi decoction markedly improved neuro-reflexes and liver and brain pathological damages, and significantly decreased the HE staging and serum biochemical indexes, and the results of high dose group was the best, similar to that of positive drug-treatment group.Conclusions Taohe Chengqi decoction exhibits promising preventive and therapeutic effects on the rat model of TAA-induced hepatic encephalopathy, and these results provide substantial experimetal evidence for its clinical application.

Objective To establish the apoptosis model in mouse cone cell line 661W cells and to investigate the viability of 661W cells in the conditions of different levels of autophagy.Methods Different concentrations of anti-Fas antibody were added to establish the apoptosis model of 661W cells,the expression of caspase-3 was detected by Western blot and the appropriate concentration of anti-Fas antibody was screened.Different concentrations of the autophagy inhibitor 3-methyladenine (3-MA) or autophagy inducer rapamycin were added to inhibit or induce autophagy,the expression of microtubule-associated protein 1 light chain 3 (LC-3) Ⅱ/LC-3 Ⅰ were detected by Western blot and the appropriate concentrations were also screened.The cultured cells were divided into 6 groups:control group,simple 3-MA group,simple rapamycin group,model group,model + 3-MA group and model + rapamycin group.Western blot was adopted to detect the expression of caspase-3,caspase-8,autophagy related genes 5 (Atg-5) and LC-3 Ⅱ/LC-3 Ⅰ at 0 hour,3,6,12,24 and 48 hours after induction.Flowcytometer was adopted to detect the apoptosis rate of 661W cells.Results The apoptosis model of 661W cells was successfully established,and the appropriate concentration of anti-Fas antibody was 2.0 μg/ml.After stimulated by the anti-Fas antibody,the expression of caspase-3 and caspase-8 of 661W cells increased from the time point of 6 hours,peaked at 12 hours,and sustained to 48 hours.However,the expression of Atg-5 and LC-3 Ⅱ/LC-3 Ⅰ raised from the time point of 3 hours,peaked at 24 hours,and decreased to the basic level at 48 hours.In addition,the appropriate concentrations of 3-MA and rapamycin were 20 nmol/L and 2.0 nmol/L,respectively.There was no statistical difference among the control group,simple 3-MA group and simple rapamycin group on the expression of caspase-3 and caspase-8 and the apoptosis rate of 661W cells at different time points (all at P＞0.05).The expressions of Atg-5 and LC-3 Ⅱ/LC-3 Ⅰ in the simple rapamycin group were significantly higher than those in the control group at different time points (all at P＜0.05).The expressions of caspase-3 and caspase-8 and the apoptosis rate in the model + 3-MA group were significantlly higher than those in the model group at 3,6,12,24 and 48 hours after induction,while the expressions of Atg-5 and LC-3 Ⅱ/LC-3 Ⅰ were obviously lower than those in the model group at 3,6,12 and 24 hours after induction (all at P＜0.05).The expressions of caspase-3 and caspase-8 and the apoptosis rate at 6,12,24 and 48 hours after induction in the model+rapamycin group were significantly lower than those in the model group,while the expressions of Atg-5 and LC-3 Ⅱ/LC-3 Ⅰ at the time points of 3,6,12 and 24 hours after induction were obviously higher than those in the model group (all at P ＜ 0.05).Conclusions Under the condition of anti Fas antibody inducing apoptosis,enhancing autophagy can reduce the apoptosis rate of cells,inhibiting autophagy can increase the apoptosis rate.Autophagy may play a protective role in 661W cells.

Objective:To analyze the consistency of the clinical phenotype of Alport syndrome between monozygotic twins.Methods:This retrospective study included identical twins with Alport syndrome who met the inclusion and exclusion criteria and were admitted to Peking University First Hospital from January 2000 to March 2019. Their clinical data and urinary epidermal growth factor (uEGF) level were extracted from the on-line registry system of hereditary kidney diseases, and analyzed retrospectively.Results:Three pairs of monozygotic twins with X-linked Alport syndrome from three non-consanguineous families were included. The consistency of the genotype status between the twins tended to confirm their monozygotic relationship. The first twins were term infants, and the twin 1A had a normal birth weight (2 500 g) while twin 1B was small for gestational age (2 450 g) . The other two pairs of twins were preterm, with different birth weights between twins 2 (2A is 2 450 g, 2B is 1 900 g) , but similar birth weights between twins 3. Although raised in the same environment, compared with twin 1A, 1B had obvious growth retardation. However, growth rate in the remaining twins were consistent. The renal abnormalities were not exactly the same between both twins 1 and twins 2, but was almost the same in twins 3. Both 1A and 1B were characterized by massive proteinuria and renal dysfunction, whereas 1B had worse renal function. At the last follow-up, 1A was diagnosed with stage 3 of chronic kidney disease (CKD) whereas 1B was CKD stage 4. Although renal function in twins 2 were normal, 2A had prominent proteinuria(24 h urinary total protein: 0.22 g) while 2B only had microalbuminuria(urinary albumin-to-creatinine ratio: 65 mg/g). Compared with the age-matched healthy controls, the concentration of uEGF normalized by urine creatinine (uEGF/Cr) were significantly lower in these twins. Besides, the twin-boy who had lower estimated glomerular filtration rates had lower uEGF/Cr. However, the extrarenal manifestations such as ocular and acoustic abnormalities were similar between the twins. Twins 2 and 3 showed bilateral temporal retinal thinning, and twins 1 both had binaural mild mid-low frequency sensorineural deafness.Conclusions:Renal manifestations of X-linked Alport syndrome in monozygotic twins may differ from each other, whereas the extrarenal manifestations including ocular and acoustic abnormalities may be consistent. Low birth weight and growth retardation may be associated with the progression of renal dysfunction.