基于生物信息学筛选炎症相关结直肠癌基因及其特征分析

目的通过对炎症性肠病差异基因的筛选以及结直肠癌队列生存特征和表达模式的探究,为炎症相关结直肠癌的发生与发展的后续研究提供候选基因。 方法从GEO数据库中选择RNA测序表达谱数据集GSE95473和GSE107597,通过常规转录组表达谱差异分析,筛选出炎症性肠病差异表达基因（DEG）,利用GO数据库获取DEG的功能注释,并利用KEGG数据库进行通路富集分析。同时基于TCGA数据库进一步在结直肠癌数据集中筛选具有预后意义的基因,并评价其在结直肠肿瘤中的表达特征。 结果两个数据集筛选到了共有DEGs 100个,通过主成分分析证实这些基因能够对结直肠癌肿瘤和黏膜区分良好。进一步筛选,获得ALDOB,SPINK4,REG4,IL1B,C2CD4A,CXCL8,NOS2,CXCL3等候选基因。这些基因在结直肠肿瘤中高表达,并且这些基因的高表达往往提示患者预后较好。 结论ALDOB,SPINK4,REG4,IL1B,C2CD4A,CXCL8,NOS2,CXCL3可能在炎症相关结直肠癌的发生发展中发挥重要作用,有待于后续炎癌转化相关功能验证和机制探究。     

Ca 19-9 serum course and prognosis of pancreatic cancer

Conclusion CA 19-9 measurement is a simple test that can be used for diagnosis as well as for prediction of resection, survival rate after surgery, and recurrences. Methods Serum expression of the tumor marker CA 19-9 was studied in 2119 patients. Results The discriminating capacity between benign and malignant disease was high for CA 19-9, especially in patients with pancreatic cancer (n=347). The sensitivity of CA 19-9 was 85%. In patients who were Lewis blood type positive, the sensitivity increased to 92%. CA 19-9 levels were significantly lower in patients with resectable tumors (n=126) than in those with unresectable tumors (n=221,p<0.0001) (sensitivity 74 vs 90%). CA 19-9 dropped sharply after resection, but normalized only in 29, 13, and 10% in patients with stage I, II, and III, respectively. In unresectable tumors no significant decrease of CA 19-9 after laparotomy or bypass operation was found. In patients of the same tumor stage, the median survival time in those whose CA 19-9 levels returned to normal after resection was significantly longer than in those with postoperative CA 19-9 levels that decreased, but did not return to normal (in stage I, 33 vs 11.3 mo, in stage II, 41 vs 8.6 mo, and in stage III, 28 vs 10.8 mo). In patients with recurrent disease, 88% had an obvious rise in CA 19-9 levels.     

Lymphocyte subset changes between 3 and 15 months of age in infants born to HIV-seropositive women in South Africa

The evolution of T‐lymphocyte subsets during infancy in perinatally HIV‐infected African babies has not been previously described. In a hospital‐based cohort study, T‐lymphocyte subset changes were investigated in 72 South African black children born to HIV seropositive mothers. Sixteen (22.2%) children were classified as infected and 56 (77.8%) as uninfected by 18 months of age. Four (25%) of the infected infants died before the age of 9 months from HIV‐related disease.
The CD4 and CD8 T‐lymphocyte subsets, expressed in absolute numbers, as percentages, percentiles or as ratios, were clear indicators of HIV infection at all ages between 3 and 15 months. The most marked changes were a decreased percentage of CD4 cells and an increase in percentage of CD8 cells in the infected group. In the 4 infected infants who died, CD8 count and CD4:CD8 ratio clearly predicted poor clinical outcome at 3 months. Taken together, both CD4:CD8 ratio and CD4 percentage are reliable markers of HIV infection in an African paediatric population; however, a raised CD8 lymphocyte count rather than a CD4 count is a more specific prognostic marker of disease progression in HIV infected children.     

Clinical significance of receptor shedding-platelet GPVI as an emerging diagnostic and therapeutic tool

Platelet membrane bedecked with a wide array of receptors offers a platform to regulate platelet responsiveness, thrombotic propensity, inflammatory disposition, and immune reactivity under diverse pathophysiological conditions. Ectopic proteolytic cleavage of such receptors irreversibly inactivates receptor-mediated intracellular signaling governing cellular functions, further releases soluble fragments into circulation which might modulate functions of target cells. Glycoprotein VI-(GPVI) is a membrane glycoprotein expressed in platelets and megakaryocytes. Platelet GPVI surface expression is enhanced following acute ischemic events like myocardial infarction and cerebral stroke, serves as an imminent diagnostic tool independent of markers of tissue necrosis, and is associated with poor prognosis. Platelets undergo GPVI shedding and thereby contribute to soluble plasma levels of sGPVI, with distinct diagnostic and prognostic attributes. This review summarizes the functional significance and mechanistic basis whereby GPVI surface availability is up- or downregulated on platelets and the impact of GPVI in diagnostic, prognostic, and therapeutic strategies in diseases where platelets play a regulatory role. Further, we also highlight how novel non-invasive platelet-based diagnostic and therapeutic strategies have evolved utilizing GPVI for lesion-directed antithrombotic therapy or to counteract atherosclerotic disposition to ameliorate care of patients particularly in the context of cardio-cerebro-vascular medicine.     

Should a platelet limit of 600 × 109/l be used as a diagnostic criterion in essential thrombocythaemia? An analysis of the natural course including early stages

In order to evaluate the natural history of essential thrombocythaemia (ET), clinical data and prognostic factors of 143 patients with ET were retrospectively analysed (mean observation time 6.1 ± 4.6 years). In 42 patients the early phase of the disease with initial platelet counts between 250 and 600 × 10⁹/l was assessed. In most early cases, ET was suggested by clinical symptoms (79%) and increased megakaryopoiesis (95%) with abnormal megakaryocytes in bone marrow histology (n = 34) and cytology (n = 5). Other myeloproliferative disorders and reactive thrombocytosis were excluded according to the diagnostic criteria of the Polycythemia Vera Study Group. During follow-up of the 38 early cases not treated cytoreductively at diagnosis, the platelet counts increased to >600 × 10⁹/l in 28 patients (74%) and remained between 450 and 600 × 10⁹/l in 10 patients (26%). In primarily asymptomatic patients (n = 46) with initial platelet counts above (n = 37) and below 600 × 10⁹/l (n = 9) the rates of increase of symptomatic patients were similar at about 7% per year. No influence of the initial platelet count on survival was seen in multivariate analysis of prognostic factors which included all 143 cases. Survival was mainly influenced by the rate of ET-related complications during follow-up (P = 0.002). Analysing the influence of cytoreductive therapy on symptom-free survival, platelet reduction benefited patients under 60 years (19 cytoreductively treated v 65 untreated patients, P = 0.075). The results demonstrate the possible clinical relevance of the early stages of ET and suggest that the features of pathologic megakaryopoiesis in the bone marrow are a more reliable diagnostic criterion than a definite platelet limit. Therefore, further therapeutic studies should include all stages of the disease and all age groups.     

Beware of hidden trains: simultaneous discovery of a MYH9‐related disease and chronic lymphocytic leukaemia

The diagnosis and follow‐up process of adult patients with acute myeloid leukaemia (AML) is challenging to clinicians and laboratory staff alike. While several sets of recommendations have been published over the years, the development of high throughput screening and characterization for both genetic and epigenetic events have evolved with astonishing speed. Here we attempt to provide a practical guide to diagnose and follow adult AML patients with a focus on how to balance the wealth of information on the one hand, with the restriction put on these processes in terms of time, feasibility and economy when caring for these patients, on the other.