Neurofibromatosis type 1 is a term of Von Recklinghausenan.It is an autosomal dominant inherited disease which derived by neural crest cell.Prevalence of this disease is 1/3000 1/3500 and is a disease with the highest mutation rate.The pathogenesis of neurofibromatosis type 1 is associated with the deficiency of NF1 gene.Recently,the genetics and genomics research of neurofibromatosis make a great progress.With the development of gene linkage and position cloning technology,the gene sequence of neurofibromatosis type 1 has been found.Recent research of genetics and genomics of NF1 and the structure and function,abnormal expression,the relation of genotype and phenotype,the mutation sensitivity domain of NF1 gene were reviewed.

Objective To investigate the relationship between exposure intensity and illumination time of blue light and replicative senescence of rat retinal pigment epithelial (RPE) ceils.Methods Thirty-six 12-14 weeks Wistar rats were kept in the cage with a blue-light bulb [(450±10) nm],and were randomly divided into four groups (no light,nature light,500 lx light and 1000 lx light illumination),each has nine rats.The rats in each group were further divided into three subgroups according to illumination time (one month,two months or three months).Eyeballs were collected after intraperitoneal injection of 10% chloral hydrate.The right eye of each rat was embedded in paraffin and sectioned for hematoxylin-eosin (HE)staining,while frozen sections of the left eye were stained for the senescence-associated β-galactosidase (SA-β-Gal).The data were analyzed by SPSS11.5 statistical software.Results The amounts of SA-β-Gal positive RPE cells were significantly different between all groups under the same illumination time 17 (P=0.000),and between all subgroups of different illumination time with same exposure intensity (P＜0.01)except for the control group (no light).Conclusion Blue-light can induce replicative senescence in rat RPE cells in an intensity and time-dependent manner.

Objective:To analyze the risk factors of neovascular glaucoma (NVG) after 25G pars plana vitrectomy (PPV) in proliferative diabetic retinopathy (PDR).Methods:A retrospective study. From January 2017 to December 2018, 340 PDR patients (340 eyes) with vitreous hemorrhage (VH) who were first treated with PPV in Tianjin Medical University Eye Hospital were included in the study. Among them, 185 were male and 155 were female, with an average age of 55.79±10.82 years. The duration of diabetes was 13.01±7.70 years, the fasting blood glucose was 7.55±2.15 mmol/L. Nineteen patients combined coronary heart disease, and 20 patients combined cerebral infarction. All patients underwent best-corrected visual acuity (BCVA), intraocular pressure (IOP), non-contact fundus examination, and fundus color photographs. BCVA was measured using an international standard Snellen visual acuity chart, and the values were converted to logarithm of the minimum angle of resolution (logMAR) scores for data analysis. The baseline logMAR BCVA was 2.04±0.73, The baseline IOP was 15.45±2.93 mmHg (1 mmHg=0.133 kPa). The duration of VH was 2.98±1.46 months, ranged from 3 weeks to 6 months. Three hundred and forty eyes included 93 eyes of PDR Ⅳ stage (27.35%), 107 eyes of Ⅴ stage (31.47%), and 116 eyes of Ⅵ stage (34.12%), combined tractional retinal detachment (TRD) 83 eyes. All patients underwent 25G standard three channel vitrectomy through the pars plana of the ciliary body. Preoperative anti-VEGF injection was performed in 57 eyes, internal limiting membrane (ILM) peeling in 234 eyes, combined phacoemulsification cataract surgery in 262 eyes and 141 eyes intravitreal anti-VEGF injection at the end of surgery. The patients were followed up for at least 12 months, with an average follow-up time of 10.80±5.79 months. NVG was defined as the presence of neovascularization in the anterior chamber angle or iris with an IOP higher than 21 mmHg after vitrectomy. Kaplan-Meier method and Cox univariate and multivariate regression were used to analyze the relationship between baseline factors, ocular factors, surgical factors and the occurrence of NVG after surgery.Results:Among 340 eyes, 66 eyes (19.41%) developed NVG after vitrectomy during 12 months of observation, NVG occurred from 6 to 335 days after surgery, and the mean period between vitrectomy and developing NVG was 98.00±5.79 days. The incidence of NVG was 11.50%, 15.29% and 20.75%, respectively in the 3rd, 6th and 12th month after PPV. The result of univariate analysis with the Cox regression analysis showed that the development of NVG at 12 months after surgery and age, combined coronary heart disease or cerebral infarction, combined with cataract phacoemulsification, ILM peeling, preoperative anti-VEGF injection had effect on postoperative NVG ( P<0.05). Ocular factors such as PDR staging, combined TRD, preoperative logMAR BCVA, preoperative intraocular pressure, etc. had no effect on the occurrence of NVG after surgery ( P>0.05). Combined cataract phacoemulsification surgery, internal limiting membrane peeling, surgical factors such as intracavity injection of anti-VEGF drugs 3 days before surgery, had an impact on the occurrence of NVG after surgery ( P<0.05). The meaningful variables of the Cox univariate analysis were incorporated into the multivariate Cox proportional hazard model for analysis, and the influencing factors of NVG after surgery were gradually regressed. The results showed that age, coronary heart disease or cerebral infarction, combined with phacoemulsification of cataract, and internal limiting membrane removal during surgery were independent risk predictors of NVG after surgery ( P<0.05). Conclusions:Younger, coronary heart disease or cerebral infarction, combined with cataract phacoemulsification are the risk factors of NVG in PDR patients after PPV. The removal of internal limiting membrane can reduce the incidence of NVG.

ObjectiveTo assess the effect of PM2.5 on sympathetic innervation and the relationship with cardiac nerve growth factor in healthy rat hearts,identify the ability to the sympathetic nerve reconstruction,and explore the possible arrhythogenic mechanism of PM2.5.MethodsForty healthy SD rats were instilled into trachea with two different solutions twice per week for four weeks:control group with saline and experimental group with PM2.5 25 mg/kg.Then these rats were killed,and biatrial appendages,two ventricular anterior walls were left.Immune cytochemical staining of cardiac nerves was performed using anti-tyrosine hydroxylase antibodies and cardiac nerve growth factor was detected by western blotting.ResuitsCompared with the control group,both the density of sympathetic nerves and the expression of cardiac NGF protein in the experimental group were much higher in the left ventricular anterior wall ( P＜0.01 and P＜0.05) and in the right ventricular anterior wall ( P＜0.01 and P＜0.05).ConclusionsPM2.5 can induce regional sympathetic hyperinnervation in both ventricular anterior walls in healthy rats by stimulating the NGF protein secretion,and the sympathetic nerve reconstruction effect of PM2.5 was confirmed.

Objective To investigate the effect of ischemic preconditioning (IPC) on the expression of a disintegrin and metalloprotease with thrombospondin type 1 motifs (ADAMTS-1), and to study whether the application of small interfering (si)RNA specifically targeting ADAMTS-1 would help to recover IPC protection in the aged heart. Methods The 32 young (4 months) and 32 aged(24 months) male Sprague-Dawley (SD) rats were assigned randomly to IPC group (n=20) and sham operated group (n= 12) respectively. Myocardial samples from the ischemic-reperfused region were harvested for detecting the ADAMTS-1 expression. In addition, the 110 aged SD rats were assignedrandomly to ADAMTS-1 siRNA group and control group (n=55, each). The effects of ADAMTS-1siRNA transfcction on the expression of ADAMTS-1 protein, myocardial infarction survival rate,heart function and myocardial infarction size after IPC were observed.Results Twenty-four hours after IPC, the ADAMTS-1 protein expression increased significantly in iscbemic-reperfused region both in young and aged rats (P＜0. 05), and the protein expression was higher in aged rats than in young rats (P＜0.05). In young-IPC group, the absorbency showed ADAMTS-1 protein expression at 0 hrs and 24 hrs after IPC were 0. 05±0.01 and 0.12±0.03 by immunohistochemical staining, and were 0.68±0. 16 and 1. 17±0.21 by Western blots respectively. In aged-IPC group, the absorbency showed ADAMTS-1 protein expression at 0 hrs and 24 hrs after IPC were 0.07±0. 03 and 0.21 ±0.04 by immunohistochemical staining, and were 0. 76±0. 21 and 1. 48±0. 17 by Western blots. In the aged rats, ADAMTS-1 siRNA transfection inhibited ADAMTS-1 protein expression (0. 66±0. 19and 0.78±0.21, by Western blots at 0 hrs and 24 hrs after IPC, P＞0.05), but didn't improve myocardial infarction survival rates [ADAMTS-1 siRNA group and sham operated group: 14.3% (5/35) vs. 17.1 %(6/35), P＞0.05], left ventricular fractional shortening [(14.0±3.2)% vs. (13.0±2.9)%, P＞0.05] and myocardial infarction size[(39.0±4.1)% vs. (38.0±5.3)%, P＞0.05].Conclusions ADAMTS-1 expression induced by IPC increases significantly in aged versus in young rats. ADAMTS-1 knockdown by siRNA inhibits ADAMTS-1 protein expression but cannot recover the age-associated loss of IPC protection.

Objective To investigate the clinical characteristics and prognosis of patients with synchronous or metachronous liver metastasis of colorectal cancer. Methods Clinical data of patients with colorectal cancer liver metastasis from 1994 to 2006 in the First Affiliated Hospital of Sun Yat-Sen University was retrospectively analyzed. The Kaplan-Meier method and long-rank test were used for bivariate comparisons. Multivariate analysis was done by the Cox regression model (Backward Wald). Results A total of 486 patients with colorectal cancer liver metastasis, including 191 synchronous and 295 metachronous liver metastasis, were analyzed. The overall 5-year cumulative survival rate was 16.2%, 9. 3% forsynchronous and 21.5% for metachronous liver metastasis respectively ( P ＜ 0. 01 ). Liver metastasis was surgically resected in 267 patients, 151 received radiofrequency ablation and 68 underwent conservative therapy with 5-year cumulative survival rates of 22. 1%, 10. 3% and 0 ( P ＜ 0. 01 ) respectively. On univariate analysis, poor prognosis was associated with older age, synchronous metastasis, higher serum CEA level, advanced N stage and poor differentiation of the primary tumor, bowel obstruction, ascites, tumor longitudinal length over 8cm, non-surgery therapy. Multivariate analysis indicated that synchronous metastasis, serum CEA level, ascites and therapy method were independent prognosis factors. Conclusions The time at which a metastasis occur, serum CEA level,ascites and curative surgical therapy determine the prognosis of patients with colorectal cancer liver metastasis. Surgical resection of metastasis in selected patients could prolong survival.

The first robotic heart surgery was performed more than two decades ago. Less invasive cardiac surgical techniques have become increasingly popular in recent years. The integration of emerging materials, computers and engineering technologies has provided the conditions for the application of robotic surgery in various cardiac procedures. Coronary artery bypass grafting (CABG), mitral valvuloplasty/valvuloplasty and radiofrequency/cryoablation for atrial fibrillation are some of the most common surgical procedures. Currently, only a few international cardiac centers have teams specializing in total endoscopic coronary artery bypass grafting. Although some studies have shown good results in robot-assisted heart surgery, questions remain about its safety, cost-benefit ratio, and long-term clinical outcomes. Robotic heart surgery poses higher challenges to myocardial protection and precise anastomosis. The role of stabilizers is to provide a relatively stable field of vision for heart surgery, which is the basis of all non-stop heart surgery. Because of their importance, researchers around the world are constantly exploring how to develop new, more sophisticated stabilizers. This review focuses on the research and development status and development trend of the stabilizer, summarizes the advantages and disadvantages of the current commonly used stabilizer, closely follows the clinic, makes in-depth analysis, and puts forward the key points of the future development of the stabilizer in coronary artery bypass surgery.

OBJECTIVETo explore the expression of cancerous inhibitor of phosphatase 2A (CIP2A) protein in small cell lung cancer and their relationship with clinicpathological features and prognosis.

METHODSA total of 112 cases of surgical specimens or bronchoscopic biopsies of small cell lung cancer were collected. There were specimens of 94 cases of SCLC tissues and 40 cases of paracancerous lung tissues. Quantitative RT-PCR and immunohistochemistry analysis were performed to determine the CIP2A expression in SCLC tissues. Kaplan-Meier curves were used to estimate the association between CIP2A expression and clinicopathological characteristics and prognosis of the patients.

RESULTSThe expression of CIP2A in SCLC tissue was 7.605 ± 1.893, significantly higher than that in the paracancerous tissues (1.041 ± 0.786) (P < 0.01). The positive rate of CIP2A expression in cancer tissues was 82.8%, significantly higher than that in the paracancerous tissues (13.3%) (P < 0.01). The median disease-free survival was 9.88 months in the CIP2A-high expressing patients, significantly shorter than the 20.92 months in CIP2A-low expressing patients (P < 0.001). CIP2A expression was significantly correlated with the tumor stage, chemotherapeutic sensitivity, and survival (P < 0.05 for all).

CONCLUSIONSCIP2A expression is associated with the pathogenesis of SCLC, and may become a potential prognostic indicator of SCLC.

Autoantigens ; metabolism ; Biomarkers, Tumor ; metabolism ; Disease-Free Survival ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lung ; metabolism ; Lung Neoplasms ; metabolism ; mortality ; Membrane Proteins ; metabolism ; Prognosis ; Reverse Transcriptase Polymerase Chain Reaction ; Small Cell Lung Carcinoma ; metabolism ; mortality

Neural stem cell is a kind of stem cells that can differentiate into neural and glial cells. While Müller cells, the main endogenous neural stem cell in retina,have the features to reentry into the cell cycle and differentiate into neural cells after retinal damage. Although it is highly effective for retinal Müller cell differentiation spontaneously after retinal injury in vertebrates, this feature is rigorous restricted in mammals. Recently, some transcription factors,such as Ascl1, Sox2, Lin28, Atoh7, are sufficient to drive quiescent Müller cells back in proliferation to generate new retinal neurons. Moreover, combining Ascl1 expression with a histone deacetylase inhibitor can bypass the limitation and increase the generation of new neurons in the adult retina. These regenerated neurons integrate the existing neuronal network and are able to respond to light, indicating that they can likely be used to restore vision. While these results are extremely promising, the regenerative response is still limited, likely because the proliferative capacity of mammalian Müller cells is low compared to their zebrafish counterparts. It is indeed necessary to identify new factors increasing the efficiency of the regenerative response.

Objective To observe the protective effect of polypyrimidine bundle-binding proteinrelated splicing factor (PSF) over-expression on RPE cell injury induced by advanced glycation end products (AGEs).Methods The human RPE cells cultured in vitro were divided into three groups:normal control group (N group),blank control group (N + AGEs group),empty vector control group (Vec + AGEs group),and PSF high expression group (PSF + AGEs).group).RPE cells in N group were routinely cultured;RPE cells in N + AGEs group were only transfected but did not introduce any exogenous genes combined with AGEs induction;Vec +AGEs group and PSF + AGEs group were transfected with pcDNA The empty vector or pcDNA-PSF eukaryotic expression plasmid was introduced into RPE cells and induced by AGEs.Except the N group,the other 3 groups of cells were transfected accordingly,and were stimulated with 150 μg/ml AGEs for 72 h after 24 h.HE staining and Hoechst 33258 staining were used to observe the effect of high PSF expression on the morphological changes of RPE cells;ROS level detection was used to analyze the effect of PSF high expression on the ROS expression of RPE cells induced by AGEs;MTT colorimetric method was used to detect the high PSF expression Effects on the viability of RPE cells;Western blot was used to detect the effects of different time and dose of PSF on the expression of heme oxygenase 1 (HO-1).Results HE staining and Hoechst 33258 staining observation showed that the cells in group N were full in shape,the nucleus was round,the cytoplasm was rich,and the staining was uniform;the cells in N + AGEs group and Vec + AGEs group were reduced in size,the eosinophilic staining was enhanced,and the nucleus was densely densely stained.Pyrolysis and even fragmentation;the morphology of cells in the PSF + AGEs group was still full,the cytoplasm staining was more uniform,and the nucleus staining was uniform.The results of MTT colorimetry showed that high expression of PSF can effectively improve the viability of RPE cells,but this effect can be effectively antagonized by ZnPP,and the difference is statistically significant (F=33.26,P＜0.05).DCFH-DA test results showed that compared with the N + AGEs group and Vec + AGEs group,the ROS production in PSF + AGEs group decreased,the difference was statistically significant (F=1 1.94,P＜0.05).Western blot analysis showed that PSF protein upregulated HO-1 expression in a time-and dose-dependent manner.The relative expression level of HO-1 at 24,48,and 72 h after PSF protein was significantly higher than that at 0 h,and the difference was statistically significant (F=164.91,P＜0.05).The relative expression level of HO-1 under the action of 0.1,0.5,1.0,1.5,and 2.0 μg PSF protein was significantly higher than 0.0 μg,and the difference was statistically significant (F=104.82,P＜0.05).Conclusion PSF may inhibit the production of ROS by up-regulating the expression of HO-1,thus protecting the RPE cells induced by AGEs.