Evidence for Chiral Wobbler in Nuclei.

Three ΔI=1 bands with the πg_{9/2}⊗νg_{9/2} configuration have been identified in _{35}^{74}Br_{39}. Angular distribution, linear polarization, and lifetime measurements were performed to determine the multipolarity, type, mixing ratio, and absolute transition probability of the transitions. By comparing these experimental observations with the corresponding fingerprints and the quantum particle rotor model calculations, the second and third lowest bands are, respectively, suggested as the chiral partner and one-phonon wobbling excitation built on the yrast band. The evidence indicates the first chiral wobbler in nuclei.

[Assessment of biomechanical properties of paraspinal muscles in adolescent idiopathic scoliosis].

Objective: To assess the bio-mechanical properties of paraspinal muscles in adolescent idiopathic scoliosis (AIS). Methods: The MyotonPro® device and shear wave elasticity imaging(SWEI) technique were applied to detect the paraspinal muscle tone (F), stiffness (S), relaxation time (R), Deborah number (C) and elasticity (D) of paravertebral muscles on the concave side and convex side of scoliosis curvature at several points: apex of the curve (a), upper (b) and lower (c) limits of the curve in 23 cases of AIS treated from October to December 2017 in Beijing Chaoyang Hospital.Cobb angle of the main curve was measured on the standing anteroposterior whole spine radiograph.Pearson correlation analysis was applied to detect the relation between the bio-mechanical properties and Cobb angle of the main curve. Results: A total of 23 AIS patients [3 males and 20 females, mean age was (15±4) years] were assessed in this study.The mean Cobb angle was (66±33) degrees.The MyotonPro® data showed that the muscle tone on the concave side were all significantly greater than those on the convex side [a: (18.9±2.2) Hz vs (17.4±1.6) Hz, t=4.435, P<0.05; b: (18.2±2.0) Hz vs (16.7±1.7) Hz, t=4.183, P<0.05; c: (18.0±2.3) Hz vs (16.8±1.7) Hz, t=4.520, P<0.05]. The muscle stiffness on the concave side were all significantly greater than those on the convex side at the three points (t=1.974, 2.048, 1.749, all P<0.05). The relaxation time were all longer on the convex side (t=-3.422, -2.713, -2.380, all P<0.05). The Deborah number were greater on the convex side at a and b points (t=-2.939, -2.466, both P<0.05). No significant difference in elasticity was found between the muscles of the two sides.The SWEI results also indicated that the elasticity of the paraspinal muscles of the two sides were similar.The Pearson correlation analysis showed that stiffness on the concave side was moderate positively correlated with Cobb angle of the main curve (r=0.582, P<0.05). Deborah number on the two sides and relaxation time on the concave were moderate negatively correlated with Cobb angle of the main curve (r=-0.632, -0.432, -0.611, all P<0.05). Conclusions: The bio-mechanical properties of paraspinal muscles in AIS are different significantly between the concave and convex side and affected by the severity of scoliosis.

Effects of lysine deficiency or excess on growth and the expression of lipid metabolism genes in slow-growing broilers.

This experiment was conducted to evaluate the effects of lysine deficiency or excess on growth and the expression of lipid metabolism genes in slow-growing birds. A total of 360 one-day-old chicks were randomly divided into 3 groups, with 6 replicates of 20 birds each. The birds fed the basal diet with a total lysine 0.60% (LL), 1.00% (ML), or 1.40% (HL). The amount of lysine (ML) as the control group, LL and HL as the experimental group, the trial period last 3 wk. The results showed that compared with ML, LL significantly decreased average daily gain and average daily feed intake and remarkably increased feed conversion ratio of birds at 21 day old (P < 0.01), while the above indices in HL had no significant effects (P > 0.05). Besides, LL reduced the pectoral muscle rate (P < 0.01) and decreased the percentage of abdominal fat significantly (P < 0.05). In addition, compared with ML, the expression of fatty acid binding protein 1 (FABP1), acetyl-CoA carboxylase (ACC), malic enzyme (ME), and sterol regulatory element binding protein 1 (SREBP1c) mRNA of liver in LL was significantly decreased (P < 0.05), and the expression of cholesteryl ester transfer protein (CETP) mRNA was significantly increased (P < 0.01), whereas LL had no significant effects on the expression of peroxisome proliferator activated receptor alpha (PPARα) mRNA (P > 0.05). Moreover, compared with ML, HL significantly reduced the expression of FABP1, ACC, ME, SREBP-1c, and PPARα mRNA in the liver (P < 0.05), and had no significant effects on the expression of CETP mRNA (P > 0.05). The results of current research suggest that dietary lysine deficiency could reduce the growth and fat deposition of slow-growing broilers mainly by downregulating the expression of lipid synthesis genes.

[Value analysis of preoperative and intra-operative ultrasound in diagnosis and treatment of parathyroid adenoma].

Objective:To explore the value characteristics of preoperative and intra-operative ultrasound in the diagnosis and treatment of parathyroid adenoma,and to further clarify the value of ultrasound in the diagnosis and treatment of parathyroid adenoma.Method:A total of 62 cases of parathyroid adenoma confirmed by postoperative pathology from March 2016 to November 2017 were collected, and the pre-operative ultrasound parameters were analyzed;and 26 cases were detected by intra-operative ultrasound.Result:In 62 cases of parathyroid adenoma, 58 cases of parathyroid adenoma were diagnosed by ultrasound before operation,and the sensitivity was 93.54%. Among the 26 cases,the lesions of 24 cases were detected by intra-operative ultrasound,and the sensitivity was 92.31%.Conclusion:Preoperative ultrasonography has a high diagnostic value for the qualitative diagnosis and location diagnosis of parathyroid adenoma, and intra-operative ultrasound can help to detect lesions quickly and safely, which is of great significance to shorten the operation time and improve the safety of operation. It is an important development space of ultrasound in the diagnosis and treatment of parathyroid glands.

Expression of CD4 is correlated with an unfavorable prognosis in wild-type NPM1, FLT3-ITD-negative cytogenetically normal adult acute myeloid leukemia.

INTRODUCTION: In the cytogenetically normal population of AML (CN-AML), FLT3-ITD-positive and wild-type NPM1 is correlated with a worse outcome, and FLT3-ITD-negative with NPM1-mut is correlated with a better outcome. This leaves a large subpopulation of CN-AML patients without NPM1 or FLT3-ITD mutations with heterogeneous outcomes with overall survivals (OS) ranging from several weeks to years. Therefore, new prognostic markers are needed to better risk stratify this subset of patients. METHODS: The retrospective study included 60 de novo adult AML patients diagnosed at our institution with normal karyotype, no FLT3-ITD or NPM1 mutations, and who did not receive allogeneic hematopoietic stem cell transplantations. We investigated the prognostic significance of immunophenotypic markers and clinical laboratory features in this double-negative population. RESULTS: Older age (>60) and CD4 expression (14%) were significantly correlated with shorter event-free survival (EFS) (P < 0.001, P = 0.016, respectively). Expression of CD56 (12%), as well as lack of CD34 expression (19% of the cases), was also associated with a worse EFS (P = 0.048, P = 0.028, respectively). On multivariable analysis, CD4 expression and old age (>60) were identified as independent predictors for worse EFS (P = 0.016; P = 0.001, respectively) and OS (P = 0.048; P = 0.028, respectively). CONCLUSIONS: Our results indicate that CD4 expression and older age are adverse prognostic factors in wild-type NPM1, FLT3-ITD-negative CN-AML.

alphaPIX nucleotide exchange factor is activated by interaction with phosphatidylinositol 3-kinase.

p21-activated kinase (PAK) is a common effector protein of the small GTPases Cdc42 and Rac, leading to the activation of downstream mitogen activated protein kinases. PAK also mediates polarized cytoskeletal changes induced by these GTPases. The recently identified PAK-interacting exchange factor (PIX) acts as a guanine nucleotide exchange factor on Rac, and colocalizes with PAK in a focal complex, but little is known about the associated signaling cascades, including upstream activators of PIX. In this study, we show that one of the isoforms of PIX, alphaPIX, is activated by signaling cascades from the platelet-derived growth factor (PDGF) receptor and EphB2 receptor, and from integrin-induced signaling through phosphatidylinositol 3-kinase (PI3-kinase). alphaPIX is activated by forming a complex with these receptors either via association with PAK and Nck, or direct association with the p85 regulatory subunit of PI3-kinase. Synthetic phosphoinositide and membrane targeted PI3-kinase augmented the alphaPIX activity in vivo. In Xenopus, aggregates of mesodermal cells derived from embryos microinjected with alphaPIX significantly increased the peripheral spreading on fibronectin substrate in response to PDGF through PI3-kinase. These results indicate that alphaPIX is activated by PI3-kinase, and is involved in the receptor mediated signaling leading to the activation of the kinase activity of PAK, and the migration of mesodermal cells on extracellular matrix.

A study on the induction of differentiation of human leukemic cells by harringtonine combined with cytarabine.

Both harringtonine (Harr) and Ara-C are effective for treatment of ANLL. Since it was suggested that Harr could induce leukemic cells to differentiate and Ara-C might be a weak inducer of leukemic cell differentiation, we investigated the effect of Harr in combination with Ara-C on inducing differentiation of leukemic cells. Ten patients with ANLL were treated with low dose Harr in combination with low dose Ara-C. Complete remission was achieved in 8 of the 10 patients. After therapy, severe pancytopenia and moderate myelosuppression occurred in two patients who achieved remission. Four patients demonstrated a decrease in blast cells with an associated transient increase in mature granulocytes during therapy. Auer bodies appeared in 7-8% mature granulocytes in peripheral blood and in bone marrow on the 14th day of combination therapy in one patient. Freshly isolated leukemic cells from six pretreatment patients were cultured in liquid in the presence of Harr in combination with Ara-C. Apparent evidence of differentiation of leukemic cells and Auer bodies in the cytoplasm of mature granulocytic cells were observed in two of the six patients. The above results seem to suggest that the therapeutic effect of low dose Harr plus low dose Ara-C may result from both differentiation induction and cytotoxicity of the leukemic cells.

Binary logistic regression analysis of solid thyroid nodules imaged by high-frequency ultrasonography, acoustic radiation force impulse, and contrast-enhanced ultrasonography.

OBJECTIVE: The common clinical techniques used for examining thyroid tumors include palpation, imaging, immunoassays and tissue biopsy. Ultrasonography is easy, non-invasive, non-radioactive and highly reproducible imaging technique; however, due to the disease polytropism, diagnosis may become difficult sometimes. Ultrasound elastography, particularly acoustic radiation force impulse (ARFI) imaging and contrast-enhanced ultrasonography (CEUS) have been successfully used to diagnose the thyroid tumors. The objective of this retrospective study was to analyze and compare the solid thyroid nodules imaged by high-frequency ultrasonography (HFUS), ARFI imaging, and CEUS. PATIENTS AND METHODS: For this purpose, images of the 80 solid thyroid nodules (58 benign and 22 malignant) with surgical pathology were obtained and data were compared using binary logistic regression analysis. RESULTS: Morphology (p < 0.001), and internal calcification (p = 0.007) were statistically different. The mean shear wave velocity (SWV) measured by ARFI was significantly different (p = 0.029). Three sets of comparison on CEUS (p = 0.019) and time to peak (TTP) of CEUS were significantly different (p = 0.001). The logistic regression analysis indicated that the morphology, mean SWV of ARFI and TTP were independent risk factors for malignancy. The diagnostic accuracy for solid thyroid nodules was 85.1% (68/80) and the area under the receiver operating characteristic (ROC) curve was 0.945±0.033. CONCLUSIONS: Logistic regression analysis can effectively screen significant parameters for the differential diagnosis of solid thyroid nodules imaged by ultrasonography.

Mutational analyses of multiple target genes in histologically heterogeneous gastric cancer with microsatellite instability.

It has been recognized that gastric cancer often shows histological heterogeneity in a single tumor. Although microsatellite instability (MSI) has been reported in gastric cancer, the significance of genomic instability in gastric cancers with histological heterogeneity within a single tumor has never been addressed. We investigated MSI at 8 microsatellite loci in 40 normal/tumor DNA pairs from 20 gastric cancers with histological heterogeneity. Six of 20 patients (10 DNAs of 40 tumor DNAs) had severe MSI in more than 3 loci. Four of the MSI-positive cases had frameshift mutations in the poly(A)10 tract of the TGF beta RII gene. This mutation was found only in the MSI-positive component in the 2 cases (cases 4 and 5) in which only 1 component exhibited MSI. The other 4 cases demonstrated homozygous or heteroclonal mutations (1 and 2 base deletions) in the poly(A)8 tract of the hMSH3 gene; no mutation was detected in the poly(C)8 tract of the hMSH6 gene in any of the MSI-positive cases. The profile of alterations in multiple targets was different between the 2 components in most of the cases (5/6). These findings suggest that mismatch repair deficiency in MSI-positive tumors causes multiple gene inactivations through frameshift mutations in short repetitive sequences in a heterogeneous way within a histologically heterogeneous tumor.

Microsatellite instability of papillary subtype of human gastric adenocarcinoma and hMLH1 promoter hypermethylation in the surrounding mucosa.

Gastric cancer has striking heterogeneity in histological pattern, cellular phenotype, genotype, biomarkers, and biological behavior. We focused on the specific morphological papillary phenotype of gastric adenocarcinoma and attempted to identify its distinct molecular characteristics. In our comparative study, early stage papillary (papillary-dominant) gastric cancer showed a significantly higher and more widespread high-frequency microsatellite instability (MSI-H) than other morphological types. Analysis of mutations in a panel of five putative microsatellite instability (MSI)-associated genes in the MSI-H cases revealed that papillary or papillary-dominant cancer displays a unique profile of mutations compared to profiles previously reported in gastric cancer. Immunohistochemical staining and methylation analysis revealed that silencing of hMLH1 by methylation in its promoter region was responsible for the failure of mismatch repair in papillary-type gastric cancer, whereas aberrant promoter methylation of hMLH1 was not found in any cases without the unique mutator phenotype. Promoter hypermethylation of the hMLH1 genes was found to a lesser degree in the adjacent non-tumor mucosa in four of the 10 cases with tumor having the mutator phenotype. Microsatellite instability itself could not be detected in the adjacent non-tumor mucosa. Inactivation of hMLH1 expression by promoter hypermethylation may be an early event in carcinogenesis of this type of gastric cancer, preceding the development of the clear MSI phenotype of papillary carcinoma.

Analyses of mutation and loss of heterozygosity of coding sequences of the entire transforming growth factor beta type II receptor gene in sporadic human gastric cancer.

Mutations in the transforming growth factor beta type II receptor (TGFbetaRII) gene have been detected in several human cancer types exhibiting microsatellite instability. Using intron primers previously reported for examination of the entire coding region of the TGFbetaRII gene, 29 sporadic gastric cancers were screened with non-radioactive single strand conformation polymorphism and subsequent DNA sequencing analysis. Mutations of the TGFbetaRII gene were detected in three out of 29 tumors (10%). Two cases showed deletions in a polyadenine tract in both alleles and was positively associated with replication error. One case had an insertion of GA dinucleotide sequence in one allele. Mutations of the TGFbetaRII gene were restricted to exon 3 and other coding regions were not affected. Loss of heterozygosity was detected by analyzing a polymorphic site in intron 2. Three out of nine (33%) informative cases, which were all of intestinal type and advanced cases, showed loss of heterozygosity but neither TGFbetaRII mutation nor replication error was found in these cases. Immunoreactivity of TGFbetaRII in tumor tissues was reduced to a different extent in the gastric cancer with genetically abnormal transforming growth factor. Although the numbers studied are small, homozygous (A)10 deletion or loss of heterozygosity of TGFbetaRII is involved in tumorigenesis and progression of at least some part of sporadic gastric cancer.

Transforming growth factor beta type II receptor (TGF beta RII) mutation in gastric lymphoma without mutator phenotype.

A new mutation in the serine-threonine kinase domain of the transforming growth factor beta type II receptor (TGF beta RII) was found in a case of diffuse, B cell non-Hodgkin's lymphoma of the stomach. A missense mutation (ACA to GCA, Thr to Ala) was detected in exon 5, and a wild type allele was also present. This is the first naturally occurring mutation in the kinase domain of this gene identified in human primary lymphoma. The replication error at three loci was negative, and the poly A tract of exon 3, which is frequently a target of mismatch repair genes, was intact. Malignant lymphoma of B cell origin in the stomach is an addition to an expanding catalogue of tumors with TGF beta RII alterations, and the biological sequelae of the change in the functional domain and the clinical characteristics of the patient in this study are intriguing.

Mxi1 mutations in human neurofibrosarcomas.

Mxi1 is thought to negatively regulate Myc function and may therefore be a potential tumor suppressor gene. Little effort has yet been made to find alterations involving this gene in human solid tumors. We screened 31 human gastric cancers, 7 esophageal cancers, 85 bone and soft tissue tumors of various types, including 4 neurofibrosarcomas. We also examined 29 human tumor cell lines consisting of 12 esophageal cancers, 7 glioma/glioblastomas and 10 others for Mxi1 mutations in exons 1, 2, 4 (HLH domain), 5 and 6. Polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and subsequent sequencing revealed three distinct polymorphisms in the intron-exon boundary upstream from exon 6. We discovered a missense mutation, GCA to GTA (Ala 54 Val), in exon 2 in a neurofibrosarcoma patient (case 1), two missense mutations, AAA to CAA (Lys 118 Gln) and GAA to GGA (Glu 154 Gly) in exon 5 of another neurofibrosarcoma patient (case 2), and 3 amino acid substitutions, GTG to GCG (Val 179 Ala), GTT to GCT (Val 181 Ala) and TTC to CTC (Phe 186 Leu), in a third neurofibrosarcoma patient (case 3). In case 3, loss of heterozygosity was also demonstrated by informative (TTC)3/(TTC)2 polymorphism. Our data demonstrate that mutations occur in the Mxi1 gene in neurofibrosarcoma. Missense mutations in the functional domain of Mxi1 in these cases may be involved in the pathogenesis of neurofibrosarcoma.

Changes in the rate of photosynthesis accompanying the yield increase in wheat cultivars released in the past 50 years.

Photosynthetic rates in different development stages were carefully investigated in 18 cultivars of winter wheat released in the period between 1945 and 1995 in the area of Beijing, China. During this period, the recorded grain yield has increased eightfold. However, when those cultivars were planted and managed in the same environment, the difference was reduced to only 36%, indicating that agronomic practices are the most important factors for grain yield. Agronomic features have changed greatly in the past 50 years, through increasing the harvest index (R2 = 0.89, P < 0.05), shortening plant height (R2 = 0.77, P < 0.05) and slightly increasing flag leaf areas (R2 = 0.45, P < 0.05), which is mostly in agreement with many other researchers. In contrast to many reports, however, this study found a genetic increase in the rate of photosynthesis per unit leaf area. From the mid-stem elongation to soft dough stages, the average photosynthetic rates at saturated photosynthetic photon flux density (P(sat)) increased by 44%. In the process, the stomatal conductance (g(s)) also increased by 122%. Grain yield was positively related to the mean values of P(sat) (R2 = 0.61, P < 0.01) and g(s) (R2 = 0.67, P < 0.01) in the six development stages. Our experiment may suggest that increase in grain yield was associated with the elevation of leaf photosynthetic rate and stomatal conductance over the past 50 years.