Low Degree Of Differentiation Research Articles

Morphogenesis of limph nodes in Muscovy ducks during early posnatal onthogenesis

The dynamics of mass and linear parameters of lymph nodes of ducks is a direct reflection of structural and functional transformations of their lymphatic parenchyma. The peculiarities of quantitative dynamics of tissue components of peripheral lymphatic organs at early stages of postnatal ontogenesis are to a great extent determined by advanced growth rates of their absolute mass against the background of sharp increase of their antigenic stimulation intensity. Parenchyma of lymph nodes of newborn ducklings is characterized by relatively low degree of differentiation and is represented by diffuse lymphatic tissue with no pronounced signs of its division into separate functional zones. Internally, the lymphatic channel is represented by only two lymphatic sinuses - the central one, which is located in the central part of the organ and occupies a large relative area and a discrete edge sinus, which borders on the node capsule and has a much smaller relative area and, accordingly, is located at its periphery. The organ parenchyma is a diffuse cluster of stromal and lymphatic cells in the enlarged lymphatic vessel between the central (inner) and edge (outer) lymphatic sinuses, without signs of its division into cortical and brain matter. Among the lymphatic tissue of the lymph node, reticular stroma cells and the population of small lymphocytes have the largest relative amount.

Immunization with Mycobacterium tuberculosis-Specific Antigens Bypasses T Cell Differentiation from Prior Bacillus Calmette-Guérin Vaccination and Improves Protection in Mice.

Despite the fact that the majority of people in tuberculosis (TB)-endemic areas are vaccinated with the Bacillus Calmette-Guérin (BCG) vaccine, TB remains the leading infectious cause of death. Data from both animal models and humans show that BCG and subunit vaccines induce T cells of different phenotypes, and little is known about how BCG priming influences subsequent booster vaccines. To test this, we designed a novel Mycobacterium tuberculosis-specific (or "non-BCG") subunit vaccine with protective efficacy in both mice and guinea pigs and compared it to a known BCG boosting vaccine. In naive mice, this M. tuberculosis-specific vaccine induced similar protection compared with the BCG boosting vaccine. However, in BCG-primed animals, only the M. tuberculosis-specific vaccine added significantly to the BCG-induced protection. This correlated with the priming of T cells with a lower degree of differentiation and improved lung-homing capacity. These results have implications for TB vaccine design.

Prognostic factors and therapeutic effects of different treatment modalities for colorectal cancer liver metastases.

BACKGROUNDColorectal cancer (CRC) is one of the most common malignant tumors in China, and the liver is the most common metastatic site in patients with advanced CRC. Hepatectomy is the gold standard treatment for colorectal liver metastases. For patients who cannot undergo radical resection of liver metastases for various reasons, ablation therapy, interventional therapy, and systemic chemotherapy can be used to improve their quality of life and prolong their survival time.AIMTo explore the prognostic factors and treatments of liver metastases of CRC.METHODSA retrospective analysis was conducted on 87 patients with liver metastases from CRC treated at the Liaoning Cancer Hospital and Institute between January 2005 and March 2011. According to different treatments, the patients were divided into the following four groups: Surgical resection group (36 patients); ablation group (23 patients); intervention group (15 patients); and drug group (13 patients). The clinicopathological data and postoperative survival of the four groups were analyzed. The Kaplan-Meier method was used for survival analysis, and the Cox proportional hazards regression model was used for multivariate analysis.RESULTSThe median survival time of the 87 patients was 38.747 ± 3.062 mo, and the 1- and 3-year survival rates were 87.5% and 53.1%, respectively. The Cox proportional hazards model showed that the following factors were independent factors affecting prognosis: The degree of tumor differentiation, the number of metastases, the size of metastases, and whether the metastases are close to great vessels. The results of treatment factor analysis showed that the effect of surgical treatment was better than that of drugs, intervention, or ablation alone, and the median survival time was 48.83 ± 4.36 mo. The drug group had the worst prognosis, with a median survival time of only 13.5 ± 0.7 mo (P < 0.05). For patients with liver metastases of CRC near the great vessels, the median survival time (27.3 mo) of patients undergoing surgical resection was better than that of patients using other treatments (20.6 mo) (P < 0.05).CONCLUSIONPatients with a low degree of primary tumor differentiation, multiple liver metastases (number of tumors > 4), and maximum diameter of liver metastases > 5 cm have a poor prognosis. Among drug therapy, intervention, ablation, and surgical treatment options, surgical treatment is the first choice for liver metastases. When liver metastases are close to great vessels, surgical treatment is significantly better than drug therapy, intervention, and ablation alone.

Mitochondrial apurinic/apyrimidinic endonuclease 1 enhances mtDNA repair contributing to cell proliferation and mitochondrial integrity in early stages of hepatocellular carcinoma

BackgroundHepatocellular carcinoma (HCC) is the leading cause of primary liver cancers. Surveillance of individuals at specific risk of developing HCC, early diagnostic markers, and new therapeutic approaches are essential to obtain a reduction in disease-related mortality. Apurinic/apyrimidinic endonuclease 1 (APE1) expression levels and its cytoplasmic localization have been reported to correlate with a lower degree of differentiation and shorter survival rate. The aim of this study is to fully investigate, for the first time, the role of the mitochondrial form of APE1 in HCC.MethodsAs a study model, we analyzed samples from a cohort of patients diagnosed with HCC who underwent surgical resection. Mitochondrial APE1 content, expression levels of the mitochondrial import protein Mia40, and mtDNA damage of tumor tissue and distal non-tumor liver of each patient were analyzed. In parallel, we generated a stable HeLa clone for inducible silencing of endogenous APE1 and re-expression of the recombinant shRNA resistant mitochondrially targeted APE1 form (MTS-APE1). We evaluated mtDNA damage, cell growth, and mitochondrial respiration.ResultsAPE1’s cytoplasmic positivity in Grades 1 and 2 HCC patients showed a significantly higher expression of mitochondrial APE1, which accounted for lower levels of mtDNA damage observed in the tumor tissue with respect to the distal area. In the contrast, the cytoplasmic positivity in Grade 3 was not associated with APE1’s mitochondrial accumulation even when accounting for the higher number of mtDNA lesions measured. Loss of APE1 expression negatively affected mitochondrial respiration, cell viability, and proliferation as well as levels of mtDNA damage. Remarkably, the phenotype was efficiently rescued in MTS-APE1 clone, where APE1 is present only within the mitochondrial matrix.ConclusionsOur study confirms the prominent role of the mitochondrial form of APE1 in the early stages of HCC development and the relevance of the non-nuclear fraction of APE1 in the disease progression. We have also confirmed overexpression of Mia40 and the role of the MIA pathway in the APE1 import process. Based on our data, inhibition of the APE1 transport by blocking the MIA pathway could represent a new therapeutic approach for reducing mitochondrial metabolism by preventing the efficient repair of mtDNA.

Tissue Microarray Detection of Estrogen Receptor, Progesterone Receptor, and C-erbB-2 in Patients with Ovarian Cancer and a Preliminary Study on the Molecular Typing of Ovarian Cancer

We evaluated the expression of estrogen receptor (ER), progesterone receptor (PR), and C-erbB-2 in patients with ovarian cancer using tissue microarrays (TMA) and preliminarily analyzed molecular typing data. Specimens from 119 ovarian cancer patients were collected and were analyzed by TMA. The expression of ER, PR, and C-erbB-2 was examined by IHC and the clinicopathological associations were analyzed. The results indicated that higher ER expression was observed in SC and EC, whereas PR exhibited a similar expression pattern, but relatively lower compared with ER expression. Conversely, very weak expression was observed in CCC and MC, especially for PR (All P &lt;0.05). C-erbB-2 exhibited no expression pattern differences among the different histological types (All P &gt;0.05), but exhibited higher positive expression in FIGO III and IV stages, whereas there was no difference in ER and PR expression among the different stages. Higher PR expression was observed in middle and highly differentiated tumors, whereas higher C-erbB-2 expression was associated with low degree of differentiation (P &lt;0.05). Patients with ER (+) PR (+) C-erbB-2 (?) had a better prognosis and patients with ER (?) PR (?) C-erbB-2 (+) had the worst prognosis. In conclusion, ER and PR tend to be highly expressed in less malignant ovarian cancer subtypes such as SC and EC. Ovarian cancer patients with ER/PR double-positive and C-erbB-2 negative expression patterns survive longer.

S2979 Type III Gastric Neuronendocrine Tumor: Case Report of a Rare Gastric Carcinoma

INTRODUCTION: Gastric neuroendocrine tumors (GNETs) are rare lesions that compromise 0.1-0.6% of all gastric cancers. The average of GNETs is 2.5 cases per 100,000 per year, with recently increased incidence in the United States due to widespread use of upper endoscopy. GNETs are classified into three groups, based on pathogenesis and histomorphologic characteristics; these types differ in biologic behavior and prognosis, ranging from benign to highly malignant with extremely poor prognosis. Type I is the major subtype of GNETs, associated with chronic atrophic/ autoimmune gastritis with pernicious anemia. Type II GNETs is associated with multiple endocrine neoplasia-1, and Zollinger-Ellison syndrome. Type III GNETs represent the second most common type, which behaves aggressively with rates of metastasis higher than 50%, and tumor related death over 25-30%. CASE DESCRIPTION/METHODS: The patient was a 63 year old who presented for reevaluation of recurrent anemia. Upon readmission, patient was found to be anemic and required PRBC transfusions. Repeat EGD showed a large 2-3cm ulcerated mass with clean base ulcer and rolled over edges in the proximal body/ greater curvature of the stomach, multiple biopsies taken. Tissue was sent for an expert opinion and was reported an unusual neuroendocrine carcinoma. Three endocrine marker stains: chromogranin, synaptophysin, and CD56, all tested strongly positive confirming the diagnosis. DISCUSSION: Type III NETs develop in the absence of hypergastrinemia, and tend to pursue an aggressive clinical course compared to Type I and Type II NETs. Type III NETs have the greatest potential to generate metastasis, with survival also being worse (75-80% at five years compared to 90-95% for Type I). They are sporadic and usually present as a single large ( >2cm) mass with normal gastrinemia. Immunohistochemical analysis is essential in GNETs, which allows diagnostic confirmation and permits classifying lesions according to histological grades. For diagnostic confirmation chromogranin A and synaptophysin are necessary; while for prognostic definition proliferation index Ki-67 and number of mitoses per high magnification field are required. Poor prognosis factors are: lesion >2cm, deep submucosal invasion or beyond; Ki-67 > 3%, vascular invasion, low degree of structural differentiation, presence of atypia and/or necrosis. Type III lesions should be managed aggressively with total or subtotal gastrectomy, if metastasis are found systemic cytotoxic chemotherapy should be provided.Figure 1.: Type III Gastric Neuroendocrine Tumor.Figure 2.: Type III GNET (retroflexion).

Characterization of KIR+ NKG2A+ Eomes- NK-like CD8+ Tcells and their decline with age in healthy individuals.

KIR+NKG2A + Eomes+ CD8+ T cells, which are preferentially found with a TEMRA (CD45RA + CCR7-) phenotype while having the capacity to rapidly produce IFN-γ in response to innate stimulation (IL-12 and IL-18), have been demonstrated to exist in human cord blood and the adult blood circulation. This highly responsive T-cell type was termed NK-like CD8+ T cells due to their capability to act in an innate immune fashion in mice similar to NK cells. However, KIR+NKG2A + CD8+ T cells that are Eomes- represent a small proportion of unconventional T cells that have not been described until now. We compare the distribution of the memory phenotypes and senescence-associated markers of two T-cell subsets by multicolor flow cytometry in 10 cord blood samples and 105 healthy individuals (HIs) ranging from 6 to 84 years of age. We found that the Eomes+ population has a higher differentiation degree than the Eomes- population. T cells in the Eomes- subset show proportionally less TEMRA phenotypes while instead preferentially displaying a more naïve and TCM phenotype. Furthermore, the Eomes- population was shown to linearly decrease with age, while the Eomes+ population exhibited more senescence-associated characteristics, such as CD57 expression and loss of CD28. Overall, the KIR+NKG2A + Eomes- CD8+ T-cell population shares similar characteristics with the Eomes+ population, although with a lower degree of differentiation, lower senescence marker expression, and a proportional decrease with age. Thus, we suspect that KIR+NKG2A + Eomes-CD8+ T cells may represent a less differentiated stage of the NK-like CD8+ T-cell subset.

Circ_0000105 promotes liver cancer by regulating miR-498/PIK3R1.

A growing number of studies demonstrate that circular RNA (circRNA) has a prominent role in the regulation of numerous biological behaviors of tumor cells. The present study aimed to investigate the expression, function and molecular mechanisms of circ_0000105 in liver cancer. A quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to obtain the expressions of circ_0000105 and miR-498 in liver cancer tissues and cells. The association between the expression level of circ_0000105 and the clinicopathological characteristics of liver cancer patients was analyzed. qRT-PCR and western blotting were utilized to investigate the expression of phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) in cells. Cell counting kit-8, bromodeoxyuridine and flow cytometry assays were utilized to determine liver cancer cell proliferation and apoptosis, respectively. Bioinformatics, a luciferase reporter gene experiment and a RNA immunoprecipitation experiment were conducted to predict and confirm the targeting correlation of circ_0000105 and miR-498, as well as miR-498 and PIK3R1. Circ_0000105 was highly expressed in liver cancer tissues and cell lines. Moreover, its high expression was associated with an increase in the T stage of liver cancer patients and a low degree of tumor differentiation. Circ_0000105 overexpression promoted liver cancer cell proliferation and inhibited apoptosis, whereas knocking down circ_0000105 triggered the opposite effect. miR-498 was a downstream target of circ_0000105, inhibiting liver cancer cell proliferation and promoting apoptosis. Mechanistically, circ_0000105 indirectly up-regulated the expression of PIK3R1 by adsorbing miR-498. Circ_0000105 plays a cancer-promoting role in liver cancer by regulating the miR-498/PIK3R1 axis.

Effects of ANCR lncRNA on the biological behaviors of lung cancer cells A549 and the mechanism.

BackgroundANCR lncRNA has been reported to participate in many cancers, but its role in lung cancer remains unclear. FOXO1 is involved in the growth inhibition and prognosis of lung cancer. We aimed to evaluate the effects of ANCR lncRNA on the biological behaviors of lung cancer cells and the mechanism.MethodsThe lung cancer and paracancerous tissues of 50 patients were collected. The expression levels of ANCR lncRNA and FOXO1 were detected by RT-qPCR and subjected to Pearson’s correlation analysis. The correlations between ANCR lncRNA expression and clinicopathological features of lung cancer patients were analyzed. The interaction between FOXO1 and ANCR lncRNA was studied by RNA pull-down and RNA immunoprecipitation assays. Human lung cancer A549 cells were transfected with lentiviral plasmids packaging ANCR lncRNA and FOXO1. The cells were divided into control group (untransfected), NC group (transfected with empty lentiviral plasmid), ANCR lncRNA group (transfected with pHRi-ANCR lncRNA), sh-ANCR lncRNA group (transfected with pHRi-sh-ANCR lncRNA), FOXO1 group (transfected with pHRi-FOXO1) and sh-ANCR lncRNA + sh-FOXO1 group (transfected with pHRi-sh-ANCR lncRNA and pHRi-sh-FOXO1). The expression levels of FOXO1 after ANCR lncRNA overexpression or inhibition were measured by RT-qPCR. Cell proliferation, cell cycle and apoptosis were detected with 5-ethynyl-2'-deoxyuridine labeling and flow cytometry respectively. Bcl-2, Bax, cyclin D1 and P27 protein expressions were detected by Western blot.ResultsCompared with paracancerous tissue, ANCR expression in lung cancer tissue significantly increased, and FOXO1 significantly decreased (P<0.01), being negatively correlated (P<0.01). The patients with higher TNM stage, lower differentiation degree and lymph node metastasis had higher relative expression of ANCR lncRNA. ANCR lncRNA bound FOXO1 and inhibited its expression. Compared with the NC group, sh-ANCR lncRNA and FOXO1 groups had fewer proliferative cells, more significant arrest in the G0/G1 phase, more apoptotic cells, increased expressions of Bax and P27, and reduced expressions of Bcl-2 and cyclin D1 (P<0.05). Compared with the sh-ANCR lncRNA group, the above results of the sh-ANCR lncRNA + sh-FOXO1 group were reversed (P<0.05).ConclusionsANCR lncRNA had high expression in lung cancer, and regulated the proliferation and apoptosis of lung cancer cells by modulating FOXO1 expression.

Studying the interrelation between the HPV infection status and the morphological features of bladder cancer.

e17003 Background: The etiological role of human papillomavirus (HPV) in the development of squamous cell carcinoma of the cervix and larynx is considered proven. At the same time, there are conflicting data in the literature on the role of HPV in the development of bladder cancer (BC). The aim of the present study was to evaluate the prevalence of HPV infection in patients with BC, identifying the relationship between the status of infection and the morphological characteristics of the tumor. Methods: The study included 46 patients (10 women and 36 men) with morphologically confirmed urothelial cancer. Samples of urine, tumor tissue and a healthy bladder mucosa were examined. HPV DNA was determined by real-time PCR. Results: 28 (60.9%) patients were infected with high-risk HPV, including 6 (60.0%) women and 22 (61.1%) men. In 14 (30.4%) patients, HPV DNA was found in the tissue of the bladder mucosa: in 6 (13.0%) cases it was only in tumor tissue, in 4 (8.7%) only in healthy mucosa, in 4 (8.7%) simultaneously in healthy and tumor tissue. HPV DNA was detected in urine in 22 (47.8%) patients. The simultaneous presence of HPV DNA in the tissue of the bladder mucosa and urine was found in 8 (28.6%) HPV-positive patients. Single HPV infection was found in 20 (71.4%) patients, two types were found in 8 (28.6%). When analyzing type diversity, it was found that HPV16 infected 14 (38.9%) patients; HPV18, 31, 39 and 56 were determined in 4 (11.1%) cases each; 33, 52 and 59 types in 2 (5.6%) cases. Chronic inflammation was noted in 12 (26.1%) patients, 6 (50.0%) of them were HPV-positive. Among HPV-positive patients, invasive cancer was registered in 18 (64.3%), non-invasive cancer in 10 (35.7%) patients. Among HPV-negative patients, these rates were 14 (77.8%) and 4 (22.2%), respectively (p &gt; 0.05). In the group of HPV-positive patients, tumors with a low degree of differentiation were found in 16 (57.1%), moderate in 6 (21.4%), high in 6 (21.4%). Among HPV-negative patients, these indicators were 4 (22.2%), 12 (66.7%) and 2 (11.1%), respectively (p &gt; 0.05). Conclusions: HPV infection was detected in 60.9% of patients, including tumor tissue infection in 21.7% of patients. The most common HPV type was HPV16. There was no statistically significant difference between HPV-positive and negative tumors.

Genetic Relationships and Reproductive Traits of Romanian Populations of Silver Fir (Abies alba): Implications for the Sustainable Management of Local Populations

Assessment of the diversity of reproductive traits and genetic variation is of great relevance to the conservation of genetic resources and management of silver fir (Abies alba) populations. We have evaluated reproductive characteristics associated with female cones and seed morphology, as well as seed germination after subjecting seeds to five storage methods, in nine Romanian populations of A. alba. The genetic diversity of the populations was assessed with 12 polymorphic simple sequence repeat (SSR) markers. We detected significant differences between populations for all reproductive traits and considerable differences in seed germination and storage methods; seed storage in wet sand was the method resulting in the highest germination in all populations. Genomic SSRs (gSSRs) were more informative on average than expressed sequence tag SSRs (EST-SSRs) in the populations studied. The nine populations were genetically diverse, with an average number of alleles (N) per SSR locus between 3.50 and 4.83. The observed heterozygosity (Ho) in the nine populations was always lower than the expected heterozygosity (He), which resulted in values of the inbreeding coefficient (Fis) between 0.261 and 0.709. Genetic distances between populations ranged between 0.077 and 0.410. The cluster analysis based on genetic distances did not group accessions according to their geographical proximity, and despite a positive trend, the correlation between geographic and genetic distances was non-significant. The results of an analysis of molecular variance (AMOVA) revealed that only 9.1% of the total molecular variance is attributable to differences between populations. This low degree of genetic differentiation between populations is confirmed by the intermingling of individuals of different populations in a principal coordinate analysis (PCoA). We found evidence of a positive relationship between He and germination, as well as a negative one between Fis and germination, suggesting that populations with low diversity and high consanguinity may have a reduced fitness and long-term viability. The results are relevant for the conservation and management of local genetic resources and populations, as well as for reforestation programmes of silver fir.

The Identification of Admixture Patterns Could Refine Pharmacogenetic Counseling: Analysis of a Population-Based Sample in Mexico.

Pharmacogenetic analysis has generated translational data that could be applied to guide treatments according to individual genetic variations. However, pharmacogenetic counseling in some mestizo (admixed) populations may require tailoring to different patterns of admixture. The identification and clustering of individuals with related admixture patterns in such populations could help to refine the practice of pharmacogenetic counseling. This study identifies related groups in a highly admixed population-based sample from Mexico, and analyzes the differential distribution of actionable pharmacogenetic variants. A subsample of 1728 individuals from the Mexican Genomic Database for Addiction Research (MxGDAR/Encodat) was analyzed. Genotyping was performed with the commercial PsychArray BeadChip, genome-wide ancestry was estimated using EIGENSOFT, and model-based clustering was applied to defined admixture groups. Actionable pharmacogenetic variants were identified with a query to the Pharmacogenomics Knowledge Base (PharmGKB) database, and functional prediction using the Variant Effect Predictor (VEP). Allele frequencies were compared with chi-square tests and differentiation was estimated by FST. Seven admixture groups were identified in Mexico. Some, like Group 1, Group 4, and Group 5, were found exclusively in certain geographic areas. More than 90% of the individuals, in some groups (Group 1, Group 4 and Group 5) were found in the Central-East and Southeast region of the country. MTRR p.I49M, ABCG2 p.Q141K, CHRNA5 p.D398N, SLCO2B1 rs2851069 show a low degree of differentiation between admixture groups. ANKK1 p.G318R and p.H90R, had the lowest allele frequency of Group 1. The reduction in these alleles reduces the risk of toxicity from anticancer and antihypercholesterolemic drugs. Our analysis identified different admixture patterns and described how they could be used to refine the practice of pharmacogenetic counseling for this admixed population.

Cancer

Cancer is a malignant neoplasm based on the uncontrolled proliferation of cells that are capable of invasion into surrounding tissues and subsequent metastasis. These cells are characterized by a low degree of differentiation – the lower it is, the more malignant the process is. Cancer has become a pandemic worldwide, yielding only to the diseases of cardiovascular system in terms of mortality. Etiology of this pathological process remains unclear. Development of medications and effective methods for the treatment of malignant neoplasms is extremely important today and it is still an unsolved scientific problem.

Lamin B1 Overexpresses in Lung Adenocarcinoma and Promotes Proliferation in Lung Cancer Cells via AKT Pathway.

PurposeThis study aims to investigate the biological effect and molecular mechanism of Lamin B1(LMNB1) in lung cancer cells and its significance for the prognosis of lung adenocarcinoma(LUAD) patients.MethodsIn this study, Bioinformatics was performed to analyze the expression at mRNA level and prognosis effect of LMNB1 in LUAD from TCGA dataset. The immunohistochemistry(IHC) assay was conducted to analyzed the expression of LMNB1 at the protein level in LUAD tissues. The correlation between the expression of LMNB1 and the clinical factors in patients with LUAD was analyzed. Next, LMNB1 transfected into LUAD cell lines (A549 and PC-9) which was proved by Western blot. CCK8 assay, cloning formation assay, and xenograft assay were conducted to explore the effect and mechanism of LMNB1 on the proliferation of LUAD cell lines in vitro and in vivo.ResultsThe results of the present study demonstrated that LMNB1 was highly expressed in LUAD tissues and related to tumor stage. High LMNB1 expression was related with more advanced clinicopathological factors such as low degree of differentiation (P=0.02), large tumor size (P<0.01), lymph node metastasis (P<0.01) and higher tumor stage (P<0.01). After knocking down LMNB1, the cell growth rate (P<0.01) and the number of colonies (P<0.01) were significantly reduced, and the level of the proliferating marker Ki67 (P<0.01) was significantly decreased. At the same time, in vivo experiments showed that the tumor volume and tumor of the mice were significantly reduced (P<0.01). Moreover, we found that knockdown LMNB1 can inhibit the proliferation of lung cancer cells by inhibiting AKT phosphorylation by Western blot.ConclusionIn summary, LMNB1 play an of vital roles in the growth of LUAD cells, highlighting its potential as a therapeutic target for the treatment of LUAD patients.

Effectiveness of Entropy Weight Method in Decision-Making

Entropy weight method (EWM) is a commonly used weighting method that measures value dispersion in decision-making. The greater the degree of dispersion, the greater the degree of differentiation, and more information can be derived. Meanwhile, higher weight should be given to the index, and vice versa. This study shows that the rationality of the EWM in decision-making is questionable. One example is water source site selection, which is generated by Monte Carlo Simulation. First, too many zero values result in the standardization result of the EWM being prone to distortion. Subsequently, this outcome will lead to immense index weight with low actual differentiation degree. Second, in multi-index decision-making involving classification, the classification degree can accurately reflect the information amount of the index. However, the EWM only considers the numerical discrimination degree of the index and ignores rank discrimination. These two shortcomings indicate that the EWM cannot correctly reflect the importance of the index weight, thus resulting in distorted decision-making results.

О ПОПЕРЕЧНОЙ ПЕТРОГЕОХИМИЧЕСКОЙ ЗОНАЛЬНОСТИ МЕЗОЗОЙСКИХ ВУЛКАНИТОВ В РУДНЫХ ПОЛЯХ ЗАБАЙКАЛЬСКОГО СЕГМЕНТА МОНГОЛО-ОХОТСКОГО СКЛАДЧАТОГО ПОЯСА

Актуальность работы обусловлена необходимостью изучения закономерностей формирования оруденения в Забайкальском сегменте Монголо-Охотского складчатого пояса. Цель работы состоит в установлении условий образования, выявлении наличия поперечной геохимической зональности в мезозойской вулканической дуге Забайкальского сегмента Монголо-Охотского складчатого пояса. Методы. Определение элементного состава пород производилось рентгенфлуоресцентным методом (ГИН СОРАН, г, Улан-Удэ). Концентрации редкоземельных элементов определялись методом сорбционно-атомноэмиссионного анализа с индуктивно-связанной плазмой (ГИН СОРАН, г, Улан-Удэ). Силикатный анализ проводился стандартным методом «мокрой химии» (ГИН СОРАН, г, Улан-Удэ). Результаты. Установлена поперечная геохимическая зональность мезозойских вулканитов Забайкальского сегмента Монголо-Охотского складчатого пояса, выраженная в увеличении концентраций от фронтальной части вулканической дуги Монголо-Охотского складчатого пояса к тыловым ее частям концентраций K, Rb, Sr, Zr, Sb, Ba, Th, U, Ce отношений K/Na, Th/U, Rb/Sr, ∑TR. Отмечена пространственная приуроченность золоторудных месторождений к фронтальной части мезозойской вулканической дуги, полиметаллических и оловополиметаллических месторождений – к тыловым ее частям. Вулканиты полиметаллических месторождений характеризуются более значительной степенью окисленности железа и меньшей степенью дифференциации магматических очагов. Окисленность железа (мера окислительных условий), соотнесенная к кремнекислотности пород в вулканитах золоторудных месторождений, варьирует от 0,19 до 0,90 (среднее значение – 0,53); в вулканитах полиметаллических месторождений – от 0,32 до 0,93 (среднее – 0,58). Такая закономерность типична для вулканитов островных дуг зон перехода континент–океан. Выявлено, что по мере удаления от фронтальной части вулканической дуги увеличиваются глубины генерации магм вулканитов Забайкальского сегмента Монголо-Охотского складчатого пояса. Такая закономерность характерна для Курило-Камчатской островной дуги. Это объясняется увеличением глубин зоны генерации магм по мере удаления от фронтальной части зоны субдукции. Глубины генерации магм вулканитов золоторудных месторождений, по данным Rb-Sr соотношений, составляют 15–20 км и более, полиметаллических и оловополиметаллических месторождений – 20–30 км и более.

MICROSATELLITE-UNSTABLE COLORECTAL CANCER IN ELDERLY PATIENTS: CLINICAL FEATURES AND THE ROLE OF IMMUNODEFICIENCY

Background. Tumors demonstrating the phenomenon of microsatellite instability (MSI) represent a special category of colorectal cancer (CRC). Such neoplasms account for up to 20 % of CRC and are characterized by specific molecular and clinical manifestations, including high immunogenicity and sensitivity to immunotherapy. MSI phenotype occurs in two different groups of patients: young individuals with Lynch syndrome and patients older than 70 years with non-hereditary CRC. We assume that the development of sporadic MSI-positive tumors in elderly patients may be associated with age-dependent decrease in immune defense. T he aim of the study was to investigate clinical and morphological characteristics in elderly patients with MSI-positive colorectal cancer. M aterial and methods . MSI status and mutations in the BRAF gene were tested in a group of 384 CRC patients older than 65 years by PCR-based techniques. A comparative analysis of clinico-pathological features was further conducted in the groups of 23 MSI-positive and 34 MSI-negative CRC cases. R esults. MSI-positive phenotype was associated with the proximal tumor location, low degree of differentiation and the presence of the mucinous component in the tumor (p&lt;0.0001, p=0.005, and p=0.0001, respectively). Patients with MSI-positive CRC containing BRAF mutations showed a significant prevalence of RhD-negative erythrocyte phenotype (53.3 % vs 11.8 %, p=0.004). In patients with MSI-positive carcinomas, the increased frequency of preoperative leukocytosis (p=0.009) and lymphopenia (p=0.014) was observed. Conclusion . The increased occurrence of Rh-negative erythrocyte phenotype and white blood formula changes in elderly patients with MSI-positive CRC may indicate the role of immune system disorders in the development of microsatellite-unstable carcinomas.

Cellular and morphological changes during leaf explant dedifferentiation and plant regeneration of Tagetes erecta

Plant tissue culture allows the maintenance of species of interest under controlled conditions. There have been few studies related to the morphological changes that take place during callus formation and redifferentiation processes. The aim of this work was to analyze the morphological changes during dedifferentiation and redifferentiation processes in leaf explants of marigold (Tagetes erecta L.) using transmission electron microscopy, digital image analysis and concepts of fractal dimension. Leaf explants were sown in MS medium supplemented with 2.0 mg L−1 of benzyladenine and 2.0 mg L−1 of 2,4-dichlorophenoxyacetic acid to induce dedifferentiation (callus formation). The redifferentiation process (bud formation) was obtained with explants sown in MS medium supplemented with 3.0 mg L−1 indoleacetic acid and 0.5 mg L−1 benzyladenine. During the first 8 days, the dedifferentiation process showed gradual changes in terms of the area and perimeter of the explants. The fractal dimension of the perimeter corresponding to the projected image of the calli changed from smooth to rough at day 20. These features indicate variations in tissue morphometry as a result of the callus formation process and further formation of cellular aggregates. Structural observations during the dedifferentiation process showed changes in shape and cellular organization as callus formation became evident. Round-shaped cells were observed in the callus, with few organelles and a low degree of differentiation. Indirect organogenesis was achieved over a period of 10 days; in addition, plantlets developed from the obtained buds in 20 days in growth regulator-free MS medium.

Serum miR-191 and miR-425 as Diagnostic and Prognostic Markers of Advanced Gastric Cancer Can Predict the Sensitivity of FOLFOX Chemotherapy Regimen.

PurposemiR-191 and miR-425 have been proved to be highly expressed in gastric carcinoma (GC). However, little research has been done on their clinical value in serum of patients with advanced GC. In addition, it is not clear whether they can be used as markers for the response and prognosis of GC patients treated with oxaliplatin combined with 5-fluorouracil and FOLFOX chemotherapy.Patients and MethodsA total of 230 patients with advanced GC admitted to our hospital were selected as the study objects, all of whom received FOLFOX chemotherapy regimen. Another 100 cases of healthy subjects were included. QRT-PCR was employed to detect the serum expression of miR-191 and miR-425 in patients.ResultsCompared with the healthy subjects, the serum expressions of miR-191 and miR-425 in GC patients were significantly upregulated, which were correlated with differentiation degree and TNM staging, respectively. According to the ROC curve, the AUC of miR-191 and miR-425 for GC diagnosis was 0.937 and 0.901, respectively, while the AUC for differentiation degree diagnosis was 0.854 and 0.822, and that for TNM staging diagnosis was 0.860 and 0.829, respectively. The predictive AUC of miR-191 and miR-425 for chemosensitivity was 0.868 and 0.835, respectively, with a combined predictive AUC of 0.935. Low differentiation degree, high TNM staging, high miR-191 and high miR-425 expressions were independent risk factors for chemotherapy insensitivity. Differentiation degree, TNM staging, chemotherapy effect, miR-191 and miR-425 were independent influencing factors for the prognosis of GC patients.ConclusionUp-regulated expression of miR-191 and miR-425 in the serum of patients with advanced GC are effective biomarkers for the diagnosis, chemotherapy and prognosis evaluation of GC.

Genetic diversity in natural range remnants of the critically endangered hirola antelope

AbstractThe hirola antelope (Beatragus hunteri) is considered to be the most endangered antelope in the world. In the ex situ translocated population at Tsavo East National Park, calf mortality and the critically low population numbers might suggest low genetic diversity and inbreeding depression. Consequently, a genetic study of the wild population is pivotal to gain an understanding of diversity and differentiation within its range before designing future translocation plans to increase the genetic diversity of the ex situ population. For that purpose, we assessed 55 individuals collected across five localities in eastern Kenya, covering its entire natural range. We used the complete mitochondrial DNA control region and microsatellite genotyping to estimate genetic diversity and differentiation across its range. Nuclear genetic diversity was moderate in comparison to other endangered African antelopes, with no signals of inbreeding. However, the mitochondrial data showed low nucleotide diversity, few haplotypes and low haplotypic differentiation. Overall, the inferred low degree of genetic differentiation and population structure suggests a single population of hirola across the natural range. An overall stable population size was inferred over the recent history of the species, although signals of a recent genetic bottleneck were found. Our results show hope for ongoing conservation management programmes and that there is a future for the hirola in Kenya.