miRNA-126-3p 与先天性心脏病肺动脉高压发病机制相关性的临床研究

目的：探讨 miRNA-126-3p 与肺动脉高压（以下简称肺高压）发病机制的相关性。方法选取25例先天性心脏病患者,其中,肺高压患者11例,对照组14例,采用 qRT-PCR 法检测其肺组织 miRNA-126-3p 的表达,并采用 starBase 进行靶基因预测,并从 mRNA 水平和蛋白水平进行验证。结果肺高压患者与对照组在年龄、性别、生化指标检查等方面比较差异无统计学意义（P＞0．05）;肺高压患者 miRNA-126-3p 表达水平与对照组比较差异有统计学意义（P＜0．01）;生物信息学预测发现 miRNA-126-3p 的生物学功能主要与结合蛋白、信号转导、细胞分化、调控细胞形态、调控 MAPK 和胰岛素受体信号通路等有关,其靶基因主要有 VEGFA 、SPRED1、PIK3R2等;肺高压组的 VEGFA 表达在 mRNA 水平和蛋白水平与对照组比较差异有统计学意义（P＜0．01）;miRNA-126-3p 与 VEGFA 呈现正相关（P＜0．01）。结论 miRNA-126-3p 可能通过调控 VEGFA 参与先天性心脏病相关性肺动脉高压发病。     

Extensively Drug-Resistant New Delhi Metallo-β-Lactamase–Encoding Bacteria in the Environment,Dhaka, Bangladesh, 2012

Carriage of the New Delhi metallo-β-lactamase variant 1 (NDM-1) enables drug resistance to move between communities and hospitals. In Bangladesh, we found the bla_NDM-1 gene in 62% of environmental waters and in fermentative and nonfermentative gram-negative bacteria. Escherichia coli sequence type (ST) 101 was most commonly found, reflecting a common global relationship between ST101 and NDM-1.     

T cell subsets and cellular immunity in end-stage renal disease

The T lymphocyte population was studied by immunofluorescent staining with monoclonal antibodies and laser flow cytometry in the blood of 50 patients with end-stage renal disease undergoing long-term maintenance intermittent hemodialysis. The absolute number of T cells was lower in patients receiving dialysis for more than one year (p less than 0.001), as was the absolute count of helper T cells (p less than 0.005). In patients under 30 years of age, the absolute number of helper T cells was markedly reduced, whereas the number of suppressor/cytotoxic T lymphocytes was not changed. In patients between the ages of 30 and 60 years, both helper and suppressor cells were significantly reduced. In patients over 60 years of age, only the number of helper T cells was reduced. The in vitro response of patients' lymphocytes was reduced both in the mixed lymphocyte reaction (p less than 0.01) and after phytohemagglutinin stimulation (p less than 0.001). Natural killer cytotoxicity of patients' peripheral blood mononuclear cells, however, was unaffected.     

A search for heterogeneity in insulin dependent diabetes mellitus (IDDM): HLA and autoimmune studies in simplex, multiplex and multigenerational families

HLA antigens (A, B, C and DR loci), serum islet cell antibodies, thyrogastric antibodies, and insulin antibodies were studied in 77 families (25 simplex, 42 multiplex, and 10 multigenerational). In order to test for intrafamilial constancy and intergroup variation, we compared simplex with multiplex families, HLA identical and non identical siblings within families, as well as groups of families characterized by different DR alleles (DR3, DR4, and DR3/DR4) for various immunologic and clinical characteristics. These comparisons did not reveal all the distinct subgroups suggested by different cross-sectional population studies, but did provide evidence for a compound form having an aggregation of different high risk alleles. This study suggests that in many cases (and possibly especially in families with multiple affected individuals), there are several different genetic influences leading to IDDM.     

The pancreatic islets in diabetes

Despite the fact that heterogeneity of diabetes in man has become more and more evident in recent years, its pancreatic pathology is still represented by two distinct entities, roughly corresponding to the classic juvenile-onset and maturity-onset types of the disease.In juvenile-onset, insulin-dependent diabetes, the pancreatic islets show severe and pathognomonic changes. B cells are greatly reduced in number already at clinical onset. Contrary to classic opinion they do not always disappear in the years to follow. Insulin's, a common finding in the pancreas of recent onset juvenile diabetic subjects, is compatible with a viral infection as well as with an autoimmune reaction as the cause of B cell destruction. In the pancreas of juvenile-onset diabetic subjects the islets, which in the past have been regarded as atrophic and inactive, are actually composed of cells containing glucagon and somatostatin. There is also a profound distortion of islet organization, and many endocrine cells are scattered as single cells in the exocrine tissue. These findings may well account for the abnormal secretory behavior of the glucagon-secreting A cells in insulin-dependent juvenile-onset diabetes.In maturity-onset, noninsulin-dependent diabetes, the pancreatic pathology is extremely variable and not pathognomonic. A numeric reduction of the B cells can be demonstrated in many maturity-onset diabetic subjects, but this reduction is much more moderate than in insulin-dependent juvenile-onset diabetic subjects and does not account for the disease. The same amount of B cell reduction can be found in many elderly subjects without clinical evidence of diabetes. In many maturity-onset diabetic subjects, the cytologic characteristics of the B cells suggest a decreased responsiveness to the stimulus of hyperglycemia. Islet fibrosis and hyalinosis (amyloidosis), although common, cannot explain this secretory dysfunction. The exact site of the defect in the B cells of maturity-onset diabetic subjects remains to be defined. Further investigations are necessary to assess the role of disturbed intraislet intercellular relationships in the pathogenesis of late-onset diabetes.The dual pattern of islet pathology in diabetes in man does not preclude a more profound heterogeneity in the etiology and pathogenesis of the disease.     

Correlation of 10-milliliter digital subtraction ventriculograms compared with standard cineangiograms

Left ventriculograms were obtained with the use of 10 ml of contrast media by passing fluoroscopic video images through a video image processor. The low concentration of dye in the left ventricle was enhanced by the technique of mask mode subtraction, and the images were postprocessed to increase visibility by manipulation of the gray scale and contrast levels. These digital subtraction angiograms were compared to standard cineangiograms by means of 40 ml of contrast media. Of 30 patients studied, six (20%) had runs of ventricular tachycardia during the cineangiogram and had to be excluded. In the remaining 24 patients, there was a good correlation between the two techniques for left ventricular end-diastolic volume (r = 0.77, end-systolic volume (r = 0.95), and ejection fraction (r = 0.97). Spatial resolution in the digital studies was adequate to appreciate wall motion abnormalities that were visualized on the cineangiograms. Left ventricular end-diastolic pressure (LVEDP) did not change after the 10 ml injection, but the mean LVEDP rose 6.0 mm Hg after the 40 ml cineangiograms (p < 0.01). Digital subtraction angiography can be used to obtain left ventriculograms with one-fourth the amount of contrast media and one-fourth the x-ray exposure compared to standard cineangiograms. This technology will permit multiple left ventriculograms to be obtained which, in turn, will allow intervention studies to be performed in the catheterization laboratory.     

Nineteen-year single-center experience in 76 patients with penile cancer treated with high-dose-rate brachytherapy

PURPOSETo report the outcomes for 76 patients with penile cancer treated with high-dose-rate brachytherapy (HDR-BT) at a single institution.METHODSSeventy-six patients with penile cancer treated with HDR-BT in our department between October 1998 and September 2018 were analyzed. Seventy underwent interstitial HDR-BT (fractionation dose range of 3–3.5 Gy given twice a day with an interval of at least six hours between the fractions), and six underwent superficial treatment with mold applicators (fractionation dose range of 4–7 Gy given once or twice a week).RESULTSMedian follow-up was 76 months (7–204 months). In the whole group, 22/76 local failures (28.9%) were observed: 14/76 (18.4%) local recurrences and 8/76 (10.5%) cases of persistent disease. Median time to recurrence was 24 months (9–54 months). Inguinal lymph node metastases were observed in 18/76 cases (23.7%). Distant metastases occurred in 12/76 (15.8%) cases. Patients with local recurrence and persistent disease underwent salvage penectomies, except four who refused surgery and underwent a second course of interstitial HDR-BT. Five- and 10-year cause-specific survival were 85.0% and 77.8%, respectively. Local control at 5 and 10 years was 65.6%. Five- and 10-year penile preservation were 69.5% and 66.9%, respectively. There was no G3 or G4 acute toxicity. One urethral stenosis (1.3%) occurred in a patient with a T3 tumor and was treated successfully with dilatation.CONCLUSIONSHDR-BT provides good local control of penile cancer and is a good option for penis preservation therapy and in our experience achieves a penile preservation rate at 10 years of 66.9%.     

血清CA125、miRNA-139-5p、miRNA-15a水平检测在卵巢癌患者中的临床意义

目的:探讨血清糖类抗原125(CA125)、微小RNA-139-5p(miRNA-139-5p)、微小RNA-15a(miRNA-15a)水平检测在卵巢癌患者中的临床意义。方法:选取74例卵巢癌患者作为卵巢癌组,选取同期74名该院健康体检者作为对照组,比较卵巢癌组与对照组、不同分化程度卵巢癌患者、不同病理分期卵巢癌患者血清CA125、miRNA-139-5p、miRNA-15a水平,分析血清CA125、miRNA-139-5p、miRNA-15a水平与卵巢癌分化程度和病理分期的相关性。结果:卵巢癌组CA125、miRNA-139-5p水平均高于对照组,miRNA-15a水平低于对照组,差异有统计学意义(P<0.05);卵巢癌低分化患者血清CA125、miRNA-139-5p水平均高于中分化和高分化患者,且中分化患者高于高分化患者;卵巢癌低分化患者miRNA-15a水平低于中分化和高分化患者,且中分化患者低于高分化患者,差异有统计学意义(P<0.05);卵巢癌患者血清CA125、miRNA-139-5p水平随着病理分期升高而升高,即Ⅰ期<Ⅱ期<Ⅲ期<Ⅳ期,卵巢癌患者miRNA-15a水平随着病理分期升高而降低,即Ⅰ期>Ⅱ期>Ⅲ期>Ⅳ期,差异有统计学意义(P<0.05);Pearson相关性分析结果显示,CA125、miRNA-139-5p水平与卵巢癌分化程度呈负相关,与病理分期呈正相关,miRNA-15a水平与卵巢癌分化程度呈正相关,与病理分期呈负相关(P<0.05)。结论:卵巢癌患者血清CA125、miRNA-139-5p水平升高,miRNA-15a水平降低,且与卵巢癌分化程度、病理分期存在相关性,血清CA125、miRNA-139-5p、miRNA-15a水平可为临床卵巢癌患者诊治提供参考依据。     

miRNA-30 b纳米粒转染对甲状腺未分化癌细胞系TA -K 细胞生物学特性的影响

目的：研究miRNA-30b纳米粒对甲状腺未分化癌细胞株TA-K细胞的生物学特性的影响。方法转染不同浓度的miRNA-30b纳米粒进入TA-K细胞中,通过流式法检测TA-K细胞凋亡情况,后通过生物信息学预测miR-NA-30b的生物学靶点,并通过RT-PCR及Western Blot方法验证。结果发现转染了miRNA-30b纳米粒后,TA-K细胞的凋亡显著增加,而生物信息学显示miRNA-30b可靶向作用于Survivin,后经RT-PCR及Western blot 法证实Sur-vivin确实是miRNA-30b的生物学靶点。结论 miRNA-30b可以通过作用Survivin促进TA-K细胞的凋亡,这一现象也为将来甲状腺未分化癌的临床治疗提供了新的思路。