Application and prospect of gene therapy for fundus vascular diseases / 国际眼科杂志(Guoji Yanke Zazhi)

Fundus vascular diseases, including neovascular age-related macular degeneration(nAMD)and diabetic retinopathy(DR), are the leading causes of visual impairment worldwide. With the accelerated aging and increased incidence of diabetes, the prevalence of these two fundus diseases will continue to rise. Currently, intraocular injection of anti-vascular endothelial growth factor(anti-VEGF)remains the first-line treatment for fundus vascular diseases, but disadvantages exist, such as frequent intraocular injections, high cost and poor compliance, thus more durable and effective therapeutic strategies need to be explored. The successful application of gene therapy in inherited retinal diseases(IRDs)provides a new idea for the treatment of fundus vascular diseases. With the ongoing of several clinical trials, gene therapy for fundus vascular diseases is expected to be employed in the clinical setting. But there still remain some concerns, including the optimal therapeutic targets selection, administration route and safety issues. This review focuses on the application and prospect of gene augmentation and gene editing-mediated anti-VEGF therapy for the treatment of nAMD and DR.

Comparative Study for the Prognosis of Intra-aortic Balloon Pump Counter-pulsation Supported Primary PCI Between Very Elderly and Elderly STEMI Patients / 中国循环杂志

Objective: To compare the prognosis of intra-aortic balloon pump (IABP) supported primary percutaneous coronary intervention (PPCI) between very elderly (age ≥ 80 years) and elderly (age < 80 years) patients with ST-segment elevation myocardial infarction (STEMI). Methods: A total of 288 STEMI patients received IABP supported PPCI in our hospital from 2004-01 to 2015-12 were retrospectively studied. Clinical condition, coronary angiography and follow-up data were analyzed; the patients with pre-operative cardiac shock, mechanical complication and non ST-segment elevation acute coronary syndrome were excluded. Eligible patients were divided into 2 groups: Very elderly group, n=51 and Elderly group, n=237. Major adverse cardiac and cerebral events (MACCE) as death, cardiac shock, new or worsen heart failure, re-MI and stroke were studied at 1 month and 1, 2 years after PPCI. Independent predictors for MACCE occurrence were investigated by Cox proportional hazard model analysis.Results: Compared with Elderly group, Very elderly group had increased incidence of MACCE at 1 month after PPCI (41.2% vs 24.5%), P=0.029 and obviously elevated incidence of stroke (9.8% vs 0.8%), P<0.001. Mortalities were similar between 2 groups at 1 month and 1 year after PPCI (17.6% vs 15.2%) and (25.5% vs 16.9%), both P>0.05; mortality was higher in Very elderly group at 2 years after PPCI (35.3% vs 20.7%), Log-rank P=0.037. Cox proportional hazard model analysis indicated that post-operative TIMI flow < 3 was the strong independent predictor for MACCE occurrence (HR=3.41, 95% CI 2.09-5.56, P<0.001), which was also the strongest predictor for death at different time points as at 1 month after PPCI (HR=9.51, 95% CI 5.23-17.29), at 1 year after PPCI (HR=7.24, 95% CI 4.13-12.69) and at 2 years after PPCI (HR=5.85, 95% CI 3.45-9.94), all P<0.001. Patients ≥ 80 years had no obvious predictors for end point event occurrence. Conclusion: Very elderly STEMI patients had the higher mortality at 2 years after IABP supported PPCI and increased incidence of MACCE at 1 month after PPCI. Patients≥80 years had no obvious predictors for end point event occurrence.

Expression and prognostic effect of DEPTOR in rectal carcinoma / 局解手术学杂志

Objective To clarify the expression of DEPTOR in rectal cancer,and to further explore the relationship between the expres-sion level of DEPTOR and histopathology and prognosis,in order to provide reference for the clinical diagnosis and treatment of rectal cancer. Methods The clinical data of 102 patients who underwent radical resection of rectal cancer in our hospital from January 2011 to January 2013 were analyzed retrospectively.The expression of DEPTOR in cancer tissues and adjacent tissues were evaluated by immunohistochemis-try and immunoblotting.The patients were divided into high expression group and low expression group by the median value of integrated opti-cal density(IOD);the relationship between the expression level of DEPTOR and clinical,histopathology and prognosis was analyzed. Results The results ofImmunohistochemistry and immunoblotting showed that the expression level of DEPTOR in cancer tissues was higher than that in adjacent tissues,the differences were significant(P<0.05). Univariate analysis showed that there was no significant differences in gender, age,and BMI(P>0.05),and there were significant differences in tumor diameter,T stage,N stage,and differentiation between the high-ex-pression and low-expression group (P<0.05).The independent influencing factors of DEPTOR expression was analyzed by the Logistic re-gression model,which showed that T stage and tumor diameter were independent influencing factors of high expression of DEPTOR.Compared with low expression group,the serum CEA level in patients with high expression group was higher,the differences was statistically significant ( P < 0.05 ). There was no significant difference in serum CA199 level between the expression group and the low expression group (P>0.05).Spearman correlation analysis showed that the expression level of DEPTOR was positively correlated with serum CEA level in rectal cancer patients (r=0.509,P<0.01).Compared with low expression group,the 5-year cumulative recurrence rate and the 5-year cumulative mortality rate in the high-expression group of DEPTOR were higher,the differences were statistically significant ( P <0.05). Conclusion DEPTOR is highly expressed and is associated with the degree of disease progression in rectal cancer,its elevation suggests a poor prognosis.

Significance of detecting free DNA from maternal plasma for the diagnosis of fetal chromosomal aneuploidies / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To determine the feasibility and accuracy of detecting numerical chromosomal abnormalities by high-flux sequencing analysis of free fetal DNA from maternal plasma.</p><p><b>METHODS</b>High-flux sequencing was applied to analyze fetal chromosome sequence copy numbers in 153 pregnant women. Fetal karyotyping was also carried out on amniocentesis samples.</p><p><b>RESULTS</b>Six cases were detected with fetal chromosomal abnormalities by high-flux sequencing analysis, among which five were confirmed by karyotyping to be chromosomal aneuploidies (47,XYY; 45,X; 47,XY,+18; 47,XY,+21 and 47,XY,+13), 1 case was confirmed to be structural rearrangement, i.e., 46,XY,der(13;21)(q10;q10),+21. Furthermore, 3 chromosomal polymorphisms (one 46,XY,21p+ and two 46,XY,Yqh-) were identified. The two methods yielded similar results on fetal chromosome copy number detection.</p><p><b>CONCLUSION</b>High-flux sequencing analysis of free DNA derived from maternal plasma is efficient for detecting fetal chromosomal aneuploidies, and is non-invasive, highly sensitive and specific. It therefore has a broad application in antenatal diagnosis.</p>