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Uveal melanoma(UM)is the most frequent and life-threatening ocular malignancy in adults.Aberrant histone methylation contributes to the abnormal transcriptome during oncogenesis.However,a comprehensive understanding of histone methylation patterns and their therapeutic potential in UM remains enigmatic.Herein,using a systematic epi-drug screening and a high-throughput transcriptome profiling of histone methylation modifiers,we observed that disruptor of telomeric silencing-1-like(DOT1L),a methyltransferase of histone H3 lysine 79(H3K79),was activated in UM,especially in the high-risk group.Concordantly,a systematic epi-drug library screening revealed that DOT1 L inhibitors exhibited salient tumor-selective inhibitory effects on UM cells,both in vitro and in vivo.Combining Cleavage Under Targets and Tagmentation(CUT&Tag),RNA sequencing(RNA-seq),and bioinformatics analysis,we identified that DOT1 L facilitated H3K79 methylation of nicotinate phosphoribosyltransferase(NAPRT)and epigenetically activated its expression.Importantly,NAPRT served as an oncogenic accel-erator by enhancing nicotinamide adenine dinucleotide(NAD+)synthesis.Therapeutically,DOT1L inhi-bition epigenetically silenced NAPRT expression through the diminishment of dimethylation of H3K79(H3K79me2)in the NAPRT promoter,thereby inhibiting the malignant behaviors of UM.Conclusively,our findings delineated an integrated picture of the histone methylation landscape in UM and unveiled a novel DOT1L/NAPRT oncogenic mechanism that bridges transcriptional addiction and metabolic reprogramming.
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Since the enrollment in 2002, the cultivation model of "4+4" program of clinical medicine in Shanghai Jiao Tong University School of Medicine has been continuously explored and practiced. With the goal of cultivating high-level compound outstanding medical innovative talents with multi-disciplinary cross-capacity, through strengthening the heuristic teaching, establishing the medical-engineering cross-course, emphasizing the training of scientific research ability, and taking teaching reform in the basic clinical single-circulation organ system integration course, we have established a talent training system with the characteristics of Shanghai Jiao Tong University School of Medicine, which is characterized by "thick foundation, strong practice, re-transformation, shaping norms, and international integration", and intend to make further exploration in the field of post-graduation education convergence.
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Learning from the clinical medicine program of North American medical schools, Shanghai Jiao Tong University School of Medicine (SJTUSM) has taken the lead in carrying out the "4+4" program of clinical medicine specialty in China since 2002, recruiting outstanding non-medical graduates to study for four years of medical courses. After 20 years of practice, SJTUSM has accumulated a series of effective school-running experience with Chinese characteristics, but there are also problems and puzzles. Based on the analysis and comparison of the "4+4" Clinical Medicine Program of SJTUSM with leading medical schools in the United States, such as Harvard Medical College and Stanford University Medical College, this paper discusses the training objectives, enrollment methods and scale, curriculum setting, degree-granting standards, etc. SJTUSM needs to strengthen the educational reform, improve the enrollment methods and curriculum system, strengthen the characteristics of compound talents training, and rationally balance the training of clinical and scientific research ability, so as to help promote the "4+4" clinical medical talents training mode to excellent.
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National education, medical industry demand and external environment all put forward the demand of training "medical + X" compound medical talents. In recent years, the development of "medical + X" has provided a foundation for the establishment of related majors in the undergraduate stage. This paper analyzes the current situation of medical interdisciplinary development at home and abroad, summarizes the existing "medical + X" training model at the undergraduate level, and argues that the new "medical + X" majors should be supported by optimizing the system design and focusing on the interdisciplinary frontier. At the same time, the setting of new majors of "Medical + X" should also pay attention to the three characteristics of livelihood, faculty and employment.
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Retinoblastoma (RB) is the most serious eye disease that causes blindness, disability and death in infant. Loss of tumor suppressor gene RB1 leads to tumorigenesis of RB. With continuous innovation and development of new methods, the management of retinoblastoma has experienced a dramatic change from enucleation, external radiotherapy, intravenous chemotherapy, to intra-arterial chemotherapy combined with local treatment, enabling a more favorable outcome for survival, salvage and vision. However, the pathogenesis of RB is unclear in many aspects, the rate of eyeball removal in children with advanced RB remains high, and the innovation of new treatment are needed to be further promoted. Therefore, the key to improve the overall treatment level of RB is to pay attention to the study on pathogenesis, early diagnosis and treatment, as well as strengthen multi-center clinical trials and translational medicine research.
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Graves′ ophthalmopathy(GO) is an autoimmune disease closely related to thyroid diseases. Clinical manifestations of GO are various, making it hard to be diagnozed and treated. There are a number of treatments available clinically, however etiological treatment remains scarce. The choice of treatment, the evaluation of therapeutic effect and the prediction of patients′ outcomes should be rooted in the evaluation of patients′ condition. In this review, the clinical characteristics of GO were analyzed, and key points of assessment including risk factors, clinical activity, disease severity, quality of life and psychological status were also proposed. Clinicians are encouraged to shed more focus on the assessment of GO.
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Thyroid-associated ophthalmopathy (TAO) is an organ specific autoimmune disease with complex pathogenesis.In recent years, great progress has been made in the pathogenesis of TAO primarily in immune and molecular mechanism aspects, including related autoantigens, lymphocytes, inflammatory factors, and autoimmune target tissue, that is, the role and biological behavior of orbital fibroblasts.Accordingly, various biological agents and immunosuppressive agents have emerged in an endless stream and have shown good effects and safety in clinical trials.Some important researches seem to be promising, but many novel therapies still are not extensively applied in clinical practice up to now.Therefore, it is of great significance to strengthen the basic research of TAO, fully understand its pathogenesis, research and develop more targeting drugs and precise clinical diagnosis and management of TAO, as well as improve the prognosis of patients.
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Dry eye affects a large number of people worldwide.A vicious cycle involving multiple factors tends to be implicated in its pathophysiology.Tear secretion is regulated by the sympathetic and parasympathetic nervous systems.Corneal nerve fibers secrete neurotransmitters and neuropeptides, which together participate in the maintenance of ocular surface homeostasis.Abnormal neuromodulation can cause abnormal tear secretion and a disruption of ocular surface homeostasis, leading to dry eye.The persistent abnormal tear film in dry eye can damage the normal repair system of ocular surface and leave the ocular surface and the lacrimal gland in a chronic inflammatory state.The cornea in dry eye patients is more sensitive to temperature change and mechanical stimulation than in healthy individuals.Symptomatic eye pain may be related to the effect of chronic inflammation on the corneal pain signal pathway.In vivo confocal microscopy and corneal esthesiometry can be used to evaluate the corneal nerve morphology and function in dry eye patients.This may ead to a more comprehensive treatment of dry eyes through the use of nerve related factors to nourish the cornea and the stimulation of neural pathways or related neural receptors to increase tear secretion.This study reviewed the relationship between neurosensory abnormalities and dry eye.
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Orbital venous malformation (OVM) is a congenital vascular disease. As a common type of vascular malformation in the orbit, OVM may result in vision deterioration and cosmetic defect. Classification of orbital vascular malformations, especially OVMs, is carried out on the basis of different categories, such as angiogenesis, hemodynamics, and locations. Management of OVM is complicated and challenging. Treatment approaches include sclerotherapy, laser therapy, embolization, surgical resection, and radiotherapy. A satisfactory outcome can be achieved only by selecting the appropriate treatment according to lesion characteristics and following the sequential multi-method treatment strategy. This article summarizes the current classification and treatment advances in OVM.
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Objective · To improve the surgical procedure of correcting upper eyelid retraction.Methods · Patients suffering upper eyelid retraction of 2-5 mm caused by thyroid-associated ophthalmopathy were treated with modified levator lengthening technique in Shanghai Ninth People's Hospital (Shanghai Jiao Tong University School of Medicine,China) from July 2013 to December 2014.Results· Of the 34 patients underwent the modified levator lengthening surgery for upper eyelid retraction correction,there were 7 males and 27 females.After 6 months,upper eyelid retraction got fully resolved in 25 cases and partly improved in 9 cases.The palpebral fissure height demonstrated an average decrease of 3.7 mm (P=0.000).Patient's ocular discomfort such as photophobia and tearing were either cured or improved.Conclusion · Modified levator lengthening surgery can effectively correct upper eyelid retraction,improve the patient's appearance and cure their ocular discomfort.
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In this paper, we present a new method which can reconstruct the three-dimensional model of nasolacrimal duct. We firstly resampled the volume data along nasolacrimal duct direction, then segmented the nasolacrimal duct into slices, and finally, completed the 3D reconstruction from the two-D contours. Using this method, we can not only reconstruct normal nasolacrimal duct, but also reconstruct catagmatic nasolacrimal duct. It overcomes the current shortcomings of some traditional methods. Consequently, the technology proposed is of great significance in computer aided technique and surgical planning related to ophthalmonogy.
Subject(s)
Humans , Image Processing, Computer-Assisted , Methods , Imaging, Three-Dimensional , Methods , Nasolacrimal Duct , Diagnostic Imaging , General Surgery , Plastic Surgery Procedures , Methods , Tomography, X-Ray ComputedABSTRACT
The curriculum construction of medical students' occupational career planning has its own character. Principles of curriculum construction siuh as practical object, professional content and target-oriented organization should be sticked to and four aspects of curriculum construction such as target,content, organization and evaluation. are discussed in detail.
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Background Many ophthalmologists have proved that the intravitreal injection of plasmin can safely induce posterior vitreous detachment(PVD),but if it can generate the complete PVD need further to seek confirmation.Researches showed that the safe dose and toxicity dose of dispase are very near,so its application is limited.Whether hyaluronidase can induce PVD is still in controversy.Objective This study is to clarity the mechanism of pharmacological vitreolysis with plasmin and hyaluronidase.Methods Plasmin 4μmol/L,2μmol/L and 1μmol/L,plasmin 1μmol/L+ hyaluronidase 20μmol/L,hyaluronidase alone were intravitreally injected in lateral eye of 4 clean New Zealand white rabbits respectively,and 0.1mL BSS was injected as control group.Electron immunocytochemical technique was used to detect the laminin and fibronectin of interface between vitreous and retina in 7 days after intravitreal injection.Other 14 eyes of 7 clean New Zealand white rabbits were used in this study.Plasmin 1μmol/L + hyaluronidase 20μmol/L was intravitreally injected in the lateral eyes,and only plasmin 1μmol/L was injected in the fellow eyes.Plasmin activity in vitreous was evaluated in 15 and 30 minutes,1 hour,2,3,6,12 hours after intravitreal injection.The use of animals followed the Regulations for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission.Results The amounts of laminin and fibronectin in the vitreoretinal interface were decreased in 4μmol/L plasmin group,2μmol/L plasmin group,1μmol/L plasmin group,1μmol/L plasmin+20μmol/L hyaluronidase group compared with control group(P＜0.01).No significant difference was seen in the density of gold particles of anti FN between 20μmol/L hyaluronidase group and control group (P＞0.05).The change of amounts of fibronectin in the vitreoretinal interface was similar to that of laminin.Plasmin activity remained the highest level 1 hour after injection and thereafter gradually decreased and extincted in 12 hours and presented the same trend between plasmin 1μmol/L+hyaluronidase 20μmol/L group and only plasmin 1μmol/L group.Conclusion The mechanism of pharmacological vitreolysis is to dissolve laminin and fibronectin in the interface between vitreous and retina and therefore induce PVD.Combination of plasmin with hyaluronidase can increase the efficiency of pharmacological vitreolysis.The optimum selection of drug in inducing PVD should consider not only its role of lysis laminin and fibronectin but also the role of liquefying the vitreous.
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Serious defect of eyelid and periorbital tissue affects the appearance of patients and closure-eye function.Application of superficial temporal artery island flap to repair the defected tissue is considered to be an available method to reconstruct eyelid and periorbital tissue.ObjectiveThis study aims to investigate the indication,safety and effectivity of reconstructing the serious defect of eyelid and periorbital tissue by forward flow flap.MethodsEighteen eyes of 18 cases with serious eyelid and periorbital tissue defect were reconstructed by covering the defect zone with superficial temporal artery to form forward flow flap.The flap was made along the distribution of superficial temporal artery with the size over the tissue detect area and transferred to lesion via subcutaneous tunnel.The follow-up time was 6 months.Survival status of flap,plastic condition of lesion and surgical treatment were discussed.ResultsAmong 18 cases with eyelid and periorbital defect,the flaps were survived in 16 cases with the satisfactory repairing appearance,showing nice color,soft texture and normal sensation after plastic surgery.Reconstructed eyelids closed well.One case showed the temporary obstruction of venous refluence in early stage after operation and remained distal epidermal necrosis.Reoperation was performed in 6 patients because of flap hypertrophy and showed a successful outcome.One patients occurred the failure of plastic flap due to hypertrophy and underwent free-flap transplantation in 3 months following the first surgery and obtained a ultimately flap survival.ConclusionThe superficial temporal artery forward flow flap offers a stable and reliable blood supplying and provides adequate tissue of excellent color and texture match.It is an ideal and available flap for the reconstruction of serious eyelid and periorbital tissue defect.
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Dacryocystorhinostomy(DCR) has been regarded as the gold standard for the treatment of nasal lacrimal duct obstruction for over a hundred years.Currently,the treatment of nasolacrimal duct obstruction has grown along with the advances in endoscopic techniques developing and in-depth understanding of the mechanisms of lacrimal drainage.Endoscopic dacryocystorhinostomy,endolacrimal laser and intubation,lacrimal endoscopic recanalization and lacrimal bypass surgery have been employed to substitute for external DCR as treatment for nasolaerimal duct obstruction.The endoscope,laser and minimally invasive techniques provide higher successful rates with minimal wounds,lower rates of both recurrence and complications and allow quicker recovery after surgery.
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Objective To investigate the effect of cyclopentolate cycloplegic on the refraction measurement in adult guinea pigs. Design Experimental study.Participants 24 eyes of 12(10 weeks) adult guinea pigs.Methods 12 animals were randomly examined thrice by streak retinoscopy pre and post mydriasis.1%cyclopentolate hydrochloride was topically administrated to the eye every five minutes for three times.Main Outcome Measures The eye refraction of guinea pigs included the scope,cylinder and the equivalent power.Results The average refraction of guinea pigs in pre-mydriasis and post-mydriasis were 1.92?0.79 D and 2.08?0.79 D respectively. The average refraction that included the scope,cylinder and the equivalent power all showed no significant difference between pre and post mydriasis.The effect of mydriasis and measure time points on the refraction that included the scope,cylinder and the equivalent scope showed no significant difference either.Conclusions The effect of 1%cyclopentolate cycloplegic on adult guinea pigs in refraction is limited.The refraction of adult guinea pig can be measured naturally without cyclopentolate cycloplegic administrated.
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The dark adapted electroretinogram was recorded in 30 eyes of New Zealand rabbits and 30 normal eyes of human volunteers.With the visual electrophy- siologic recording system,each eye being tested with intensities of a range of 5 log units,to study the intensity-response function of the scotopic b- wave of electroretinogram.It was found that the intensity-response function of the scotopic b-wave was a sigmoidal curve which fitted to the Naka- Rushton Equation:R/Rmax=I~n/(I~n+K~n)only at low to moderate flash luminances:at high flash lumi- nances,a second limb appeared in the function,which represented a complex combination of the rod system response and the cone system response.