Objective: To investigate the effects of long-term hyperglycemia on renal pathology of type 1 diabetic mellitus(T1DM) cynomolgus monkeys by establishing streptozotocin(STZ)-induced T1DM. Methods: Eight 4-year-old male cynomolgus monkeys were randomly divided into control and model groups. Four cynomolgus monkeys were used in the control group, and four cynomolgus monkeys were injected with streptozotocin to create a T1DM model. Hematoxylin-eosin(HE) staining and periodic acid-Schiff(PAS) staining were used to observe renal pathological changes.The histological characteristics and changes were observed under transmission electron microscope. Morphometric measurements were used to analyze the glomerular area, the thickness of the glomerular basement membrane, the proportion of glomerular podocyte foot processes and the average area of foot processes. Results: In comparison to the control group, the model group showed pathological changes in the kidneys, including increased glomerular area(P<0.01), thickened basement membrane, capillary loop compression, disordered arrangement of endothelial cell fenestrations, proliferation of mesangial cells, mesangial expansion, accumulation of mesangial matrix glycoproteins, a decrease in the number of foot processes(P<0.001), a decrease in the average size of the foot processes(P<0.05), widened podocyte slit diaphragm, and an increase in the number of fused foot processes(P<0.001). Conclusion Cynomolgus monkeys with T1DM suffer from renal pathological changes due to long-term hyperglycemia.

Objective To explore the efficacy and safety of evolocumab in elderly patients with high-risk cardiovascular diseases.Methods A total of 153 patients with poor lipid control after conventional statin therapy who were hospitalized in the cardiologic departments in the First,Sec-ond,Sixth and Eighth Medical Centers of Chinese PLA General Hospital from November 2019 to November 2022 were included,and divided into non-elderly group(＜60 years old,46 cases),eld-erly group(60-74 years old,66 case)and very elderly group(≥75 years old,41 cases).They were all given evolocumab treatment according to guidelines.Another 50 over-75-year-old patients with high-risk cardiovascular diseases and poor lipid control who were hospitalized in the above cardiologic departments during the same period were treated with a statin drug combined with ezetimibe,and served as conventional treatment group(control group).The baseline clinical data and the blood indicators at 4th and 12th week after drug administration,and the occurrence of ad-verse drug reactions and major adverse cardiovascular events(MACE)within 12 weeks were com-pared among the groups.Results The levels of LDL-C and TC were significantly decreased in the three evolocumab treatment groups at 4 and 12 weeks after medication when compared with the baseline values(P＜0.05,P＜0.01),but there were no obvious differences in the 2 levels among the 3 groups at 12 weeks(P＞0.05).At the time point,no statistical difference was observed in the incidence of adverse events in the three groups(2.2％vs 3.0％vs 2.4％,P＞0.05).The levels of LDL-C and TC were decreased significantly in the very elderly group and the conventional treatment group at the 12th week when compared with the baseline levels(P＜0.05,P＜0.01),and the LDL-C level at the week was notably lower in the very elderly group than the convention-al treatment group(1.36±0.44 mmol/L vs 1.87±0.56 mmol/L,P＜0.01).But no difference was seen in the incidence of MACE between the 2 groups(12.2％vs 16.0％,P＞0.05),either in sur-vival rate between them(P=0.576).Conclusion For patients of all ages,evolocumab has good short-term efficacy in lipid control,and for those over 75 years old,the drug also shows good effi-cacy and sound safety.

Objective:To explore the effect of constructing WeChat platform and introducing PPT (PowerPoint) optimized by Media studio pro editing technology in the teaching of radiation therapeutics.Methods:Sixty undergraduates of medical imaging technology in Fujian Medical University were randomly divided into experimental group and control group in average. The experimental group set up a WeChat group and acquired the optimized PPT before class; control group received classroom teaching and clinical practice according to the traditional teaching mode. Twenty-four items of MCTQ (Maastricht clinical teaching questionnaire) were selected and translated. A total of 30 teachers majoring in tissue radiation oncology and medical imaging were randomly divided into two groups. The questionnaire was used to evaluate the two teaching models. To examine the academic performance of the two groups of students. SPSS 23.0 software was used for independent sample t-test. Results:By comparing the scores of MCTQ questionnaire between the two groups, it was concluded that the teaching mode of the experimental group had significant advantages in 11 aspects, such as clinical practice, obtaining more learning opportunities and so on ( P < 0.05). The scores of practice [(84.67±7.29) vs. (80.03±8.97)] and final evaluation [(81.53±8.78) vs. (76.77±9.49)] of the students in the experimental group were better than those in the control group ( P < 0.05). Conclusion:The application of optimized PPT by Media studio pro editing technology based on WeChat platform is worth popularizing in the teaching of radiation therapeutics.

Objective: To investigate the effects of long-term hyperglycemia induced ultrastructure of left ventricular myocardium in streptozotocin-induced type 1 diabetes mellitus(T1 DM) cynomolgus monkeys. Methods: The T1 DM cynomolgus monkeys were induced by intravenous administration of streptozotocin as the model group. The normal cynomolgus monkeys were distributed to the control group. Ultrastructural morphometric features of left ventricular myocardium in the model group and the control group were obtained using transmission electron microscope and quantitatively analyzed. Results: Ultrastructural observations indicated that the numbers of mitochondrion(P<0.01), the relative electron density of mitochondrion(P<0.000 1), the volume density(P<0.001) and the surface area density(P<0.05) of mitochondrion were observed to decrease in the cytoplasm of left ventricular cardiomyocytes of the model group compared to the control group. The ration surface and the average area of mitochondrion showed no difference between two groups. Massive lipid droplets were identified in the cytoplasm of left ventricular cardiomyocytes of the model group. Thickening of basement membrane(P<0.000 1) and decreasing of pinocytotic vesicles(P<0.000 1) were observed in the capillary endothelial cells in left ventricular myocardium of the model group compared to the control group. Conclusion The results indicate that long-term hyperglycemia induces left ventricular cardiomyocytes and capillary endothelial cells ultrastructural damage in TIDM cynomolgus monkeys.

[摘 要] 目的：基于已发表的芯片数据通过生物信息学方法筛选差异表达基因，以发现前列腺癌诊断/预后和耐药相关分子标志物。方法：筛选GEO数据库中已发表的前列腺癌mRNA芯片数据GSE6956和前列腺癌细胞多烯紫杉醇耐药mRNA芯片数据GSE33455进行差异表达分析；通过生物学功能注释、基因通路富集分析、蛋白质相互作用网络（protein-protein interaction，PPI）分析等生物信息学方法发现和识别与差异表达基因相关的生物学功能和信号通路；比对TCGA数据库，验证差异表达基因在前列腺癌组织及癌旁组织中的表达，并通过Kaplan-Meier分析差异表达基因对前列腺癌患者生存率的影响；用qPCR方法验证差异表达基因在前列腺癌细胞株PC3及多烯紫杉醇耐药细胞PC3-DTX中的表达情况。结果：共筛选出227个在前列腺癌和前列腺癌多烯紫杉醇耐药细胞芯片数据中共同差异表达基因。差异表达基因主要富集到了癌症相关通路（Lysosome、Sphingolipid、FoxO、Acute myeloid leukemia），并主要参与细胞黏附、自噬和胞内蛋白转运等生物学过程。构建PPI网络选取18个连接度最高的基因作为Hub基因。Hub基因和共同差异表达基因中，上调基因CITED2、LRP12和RPL17-C18orf32与前列腺癌患者的不良预后显著相关。qPCR验证显示CITED2在多烯紫杉醇耐药细胞PC3-DTX中高表达。结论：通过生物信息学方法筛选出在前列腺癌组织和耐药细胞中共同差异表达，且与前列腺癌患者的不良预后密切相关的基因，为前列腺癌诊断/预后和耐药分子标志物的研究提供了新的思路。

Objective This study was conducted to establish a stable and highly efficient method for isolation and purification of pancreatic islets from NOD mice and to evaluate their characteristics in vitro and in vivo. Methods The is-lets were isolated from mouse pancreas using modified collagenase digestion and Ficoll density gradient centrifugation. The endocrine secretory function was assessed by insulin secretion in either low or high dose glucose stimulation. To evaluate the function of the graft,body weight and blood glucose were monitored,and IVGTT was performed. In addition,to assess sur-vival of the implanted islets,Pathology using HE staining and insulin immunostaining of the graft were performed. Results The average islet yield was 116 ± 12 islets/pancreas and purity was higher than 90%. Compared with islets from Kunming mice,the islets isolated from NOD mice were poorly responsive to glucose challenge. Blood glucose levels and body weight changes of the islet-transplanted diabetic mice were significantly improved compared with the sham-operated mice. In addi-tion,blood glucose levels in vivo after an IVGTT also significantly improved. However,these improvements were only main-tained for 2 weeks. Furthermore,HE staining and immunostaining assays demonstrated that there were insulin-positive cell clusters and lymphocyte infiltration in the graft-bearing kidney. Conclusions A large number of quality islets can be isola-ted and purified from NOD mice by using the modified mouse islet isolation method, which can be used to develop thera-peutic strategies to protect transplanted islets from rejection and autoimmune attack.

Objective To comparatively analyze the image characteristic of contrast-enhanced ultrasound(CEUS)and contrast-enhanced computed tomography(CECT),and explore the diagnostic value of the two methods in benign and malignant lesions of gallbladder.Methods comparative analysis the image characteristic of CEUS and CECT,the preoperative diagnostic results of 86 cases of gallbladder diseases were confirmed by pathology.Results The enhancement patterns of CEUS and CECT in benign and malignant lesions of gallbladder are similar.The sensitivity,specificity and accuracy of CEUS were 77.9%(53/68),77.8%(14/18),77.9%(67/86),respectively.The sensitivity,specificity and accuracy of CECT were 75%(51/68),55.6%(10/18),70.9%(61/86),respectively.The sensitivity,specificity and accuracy of the combination of CEUS and CECT were 83.8%(57/68),55.6%(10/18),77.9%(67/86),respectively.The accuracy of the combination of CEUS and CECT was higher than that of CECT in the diagnosis of malignant gallbladder lesions [(53.9±10.00)s vs(35.50±6.72)s],the differences were statistically significant(t=6.729,P＜0.001).Conclusions The enhancement patterns of CEUS and CECT in benign and malignant gallbladder lesions are similar.The combination of CEUS and CECT is helpful for improving the diagnostic accuracy of malignant gallbladder lesions.CEUS and CECT could corroborate and complement each other,and provide more valuable information for the differential diagnosis of benign and malignant gallbladder lesions.

Objective To compare clinical data of the death in different intensive care unit,in order to provide the medical strategies for patients in EICU.Methods The clinical data of lethal cases from January 1,2013 to December 31,2014 in EICU,SICU and MICU of the First Affiliated Hospital of Sun Yat-sen University were compared.EICU (252 cases),SICU (93 cases) and MICU (80 cases) were enrolled.The demographics of each patient,clinical condition such as critical score (APACHE Ⅱ score),length of stay,overall costs,and the patient families' different opinions to the treatment in each ICU were analyzed.The data was analyzed with SPSS 13.0 software,averaged value was presented as mean ± standard and the non-normal distributions were expressed as median (25％,75％).The one-way analysis of variance was followed by the Tukey post hoc test for pairwise comparisons and chi-square test was used for comparison of percentage between two groups.Results Two hundred and fifty-two cases in EICU had gender ration of 148/96 (male/female),92 cases in SICU 68/24,80 cases in MICU 56/24.Ages of the fatal were EICU 72 ± 17 years,SICU 56 ± 17 years,and MICU 63 ± 20 years,respectively.Age of the fatal in EICU was significantly older than that of the SICU (P ＜ 0.01) and the MICU (P ＜ 0.01).APACHE Ⅱscores were 33 ± 8 in EICU,34 ± 10 in SICU,29 ± 10 in MICU,respectively.The severity scores in EICU patients were higher than those in MICU patients and SICU patients (P =0.01 and 0.021).Lengths of stay were 2 days (1,46) in EICU,14 days (1,84) in SICU,12 days (1,77) in MICU,respectively.EICU hospitalization time was significantly shorter than that of SICU (P ＜ 0.01) and the MICU (P ＜ 0.01).Total costs of hospitalization were 9 777 yuan (400,164 126) yuan in EICU,100 628 yuan (13 639,964 783) yuan in SICU,119 463 yuan (5 650,590 903) yuan in MICU,and that in EICU was significantly less than the total cost of hospitalization in SICU (P ＜ 0.01) and in MICU (P ＜ 0.01).The opinion of patient families was proposed to give up treatment associated with 165 dead cases in EICU,18 death cases in SICU and 20 dead cases in MICU,and the rate of discontinuous treatment in EICU patients was significantly greater than that in SICU (P ＜ 0.01) and in MICU (P ＜ 0.01).There were no significant differences in invasive procedures,invasive hemodynamic monitoring,mechanical ventilation,blood purification and deep vein puncture among three groups.The 5 leading causes in EICU were severe sepsis,stroke,sudden cardiac arrest,acute myocardial infarction and advanced malignancy.Conclusions The death of patients were due to advanced age with severe disease,poor prognosis,and the request of patient family members to give up treatment.The 5 leading causes were severe sepsis,stroke,sudden cardiac arrest,acute myocardial infarction and advanced tumors suggesting the establishment of corresponding treatment scheme to be made and preparation of abundant medical resources to be ready.Timely communication with the patients' families and let them participate in end-stage treatment decisions was the best strategies to improve the successful rate of treating severe patients and use EICU resource effectively.

Chronic kidney disease (CKD) is a chronic renal structure change and dysfunction caused by a variety of causes.The incidence and prevalence of CKD have been on the rise,becoming a major global health problem.An increasing number of studies had shown that one of the important indicators of CKD progression was the disorder of gut microbiome and elevated levels of sernm endotoxin.Modern physicians of traditional Chinese medicine (TCM) believed that the main pathogenesis of CKD was spleen and kidney deficiency.And the therapeutic regimen was invigorating spleen and nourishing the kidney.Spleen is in the middle burner.It has the function of transportation and resistance to evil,which was extremely similar to the function of gut microbiome in metabolism and immunity.The latter might be one of the biological bases of physiological function of spleen.This comprehensive review presented the modern theoretical basis of spleen-based TCM treatment methods for CKD from the insight of modern gut microbiome and metabolism.Firstly,gut microbiome and its metabolism were associated with the spleen in TCM theory.Gut microbiome affected individual metabolism and immune function,which could provide a modern biological basis for explaining the physiological function of the spleen.Secondly,gut microbiome and its metabolism were correlated with CKD:intestinal flora disturbance occurred in CKD patients,producing enterogenous toxins as their metabolites,which become the important factors affecting prognosis.Thirdly,as for its origin,development and current status based on the spleen theory,CKD was one of various consumptive diseases.Spleen insufficiency was one of their critical pathogenic mechanisms.Therefore,tonifying the spleen should be a treatment method to maintain throughout the entire treatment.On the basis of our previous clinical studies and the hypothesis of gut microbiome and metabolism,we proposed further studies which were also based on system biology and its technology.

[Summary] The epithelial‐mesenchymal transition (EMT) is a biological process in which epithelial cells are converted into cells with mesenchymal phenotype in specified physiological and pathological conditions. EM T plays a critical role in proper embryonic development ,tissue regeneration ,cancer metastasis and organ fibrosis. EM T can be divided into three subtypes (Ⅰ ,II and Ⅲ ) based on different biological context ,of which type II EMT contribute importantly to the development of organ fibrosis.Renal interstitial fibrosis (RIF) is an important pathological feature of diabetic nephropathy (DN). The understanding of molecular mechanisms of this process tubular EM T may provide a clue to intervene the development of DN through suppressing EM T and reversing RIF.