[Study of neurotrophic factor receptor tyrosine kinase gene fusion in the precise treatment of wild-type gastrointestinal stromal tumor].

The neurotrophin receptor kinase (NTRK) gene encodes neurotrophic factor receptor tyrosine kinase (NTRK), which plays an important role in the development and function of the nervous system. NTRK gene fusion mutation results in the production of chimeric NTRK proteins, which have carcinogenic potential through constitutive activation or overexpression. NTRK gene fusion mutation can lead to a special type of wild type gastrointestinal stromal tumor (GIST), whose clinical manifestations and treatment are completely different from other types of GIST. This fusion mutation can be detected clinically by a variety of methods, including tumor DNA and RNA sequencing and immunohistochemical staining. In patients with NTRK fusion positive tumors, NTRK inhibitors such as larotrectinib and entrectinib have shown good antitumor efficacy, with clinical response rates as high as 75%. Therefore, there is a need to improve the recognition and detection of fuch patients and to improve their prognosis by individualized and precise treatment with TRK inhibitors.

[Effect of early-life antibiotic exposure on allergic symptoms in children aged 6-11 months and 18-23 months based a birth cohort study].

Objective: To analyze the associations between prenatal and 1-year-old exposure to antibiotics and allergic symptoms in children aged 6-11 months and 18-23 months. Methods: In this study, a prospective birth cohort study was adopted. A total of 2 122 pregnant women were enrolled in Maternal and Child Health Care Center of Ma'anshan from June 2015 to June 2016, and they were followed up from the beginning of pregnancy to children's 24 months of age. Excluding 564 pairs of mothers and children who were lost to follow-up or with incomplete information on the use of antibiotics and children's allergic symptoms, a total of 1 558 pairs of mothers and children were included in the analysis of this study. The parents and children's general demographic information, early-life antibiotic exposure and other data were collected, the information about allergic symptoms in children aged 6-11 months and 18-23 months were investigated by reference to the "International Study of Asthma and Allergies in Childhood (ISAAC)". The univariate and multivariate binary unconditional logistic regression model was used to was used to estimate associations between the effects of early-life antibiotic exposure on allergic symptoms in 2-year-old children. Results: The antibiotic usage rate of pregnant women during pregnancy was 3.4% (53), and the antibiotic usage rates of children between 0 to 2 months, 3 to 5 months, and 6 to 11 months were separately 15.2%(237), 15.5%(242) and 17.3%(269). The total prevalence of allergic diseases in children aged 6 to 11 months was 24.1% (375 children), and the total prevalence of allergic diseases in children aged 18 to 23 months was 22.0% (342 children). After adjust parental (maternal) education level, family monthly income per capita, parental (maternal) allergy history, parental (maternal) age at pregnancy, mother's Body Mass Index (BMI) before pregnancy, exposure to second-hand smoke during pregnancy, delivery method, child gender, birth weight, preterm birth, the use of antibiotics when children were 3-5 months old (RR=1.61,95%CI:1.19-2.17) and 6-11 months old (RR=1.43,95%CI:1.06-1.93) were the risk factors for allergic symptoms at 6-11 months of age; and the use of antibiotics when children were 0-2 months old (RR=1.41, 95%CI: 1.03-1.95), 3-5 months old (RR=1.54, 95%CI: 1.12-2.11) and 6-11 months old (RR=1.58, 95%CI: 1.17-2.14) were the risk factors for allergic symptoms at 18-23 months of age. Conclusion: Children's exposure to antibiotics within 1 year of age was a risk factor for allergic symptoms in children aged 6-11 months and 18-23 months, children should avoid unnecessary antibiotic use in infancy.

[Pre-pregnancy BMI, gestational diabetes and different indicators of childhood obesity at the age of four: a prospective cohort study].

Objective: To examine the relationship between pre-pregnancy BMI, gestational diabetes (GDM) and different indicators of childhood obesity at the age of 4. Methods: Based on Ma'anshan Birth Cohort Study, singleton children who were born in Ma'anshan of Anhui province from October 2013 to April 2015, were followed for 4 years, consecutively. During the first questionnaire survey, data including pre-pregnancy weight, height and socio-demography were collected. During 24-28 week of gestation, 75 g oral glucose tolerance test was conducted for them. Childhood height, weight, waist circumference and body composition were measured at the age of 4. Comparisons between groups were performed using chi-square test, analysis of variance or t-test. The relationship between pre-pregnancy overweight/obesity, GDM and childhood obesity-related characteristics were analyzed by logistic regression model and generalized linear model analysis. Results: The prevalence rates of overweight and obesity in children at the age of 4 were 13.08% and 6.03%, respectively. After adjustment for characteristics related to mothers and their children, significantly increased risk of obesity (OR=3.27, 95%CI: 2.15-4.98), larger waist circumference (OR=2.32, 95%CI: 1.72-3.14) and higher waist-to-weight ratio (OR=2.29, 95%CI: 1.73-3.02) were seen in the offspring of women with pre-pregnancy overweight/obesity. Body composition (skeletal muscle, body fat, body fat percentage) of the offspring were strongly correlated with pre-pregnancy overweight/obesity of the mothers (P<0.05). Maternal GDM was associated with higher risk of childhood obesity (OR=1.78, 95%CI: 1.14-2.79), on mothers without GDM during pregnancy. However, neither larger waist circumference, or higher waist-to-weight ratio seemed to increase the risk. Moreover, maternal GDM was not associated with body composition measures (skeletal muscle, body fat, body fat percentage). Conclusion: Pre-pregnancy BMI and maternal GDM were independent risk factors for obesity in 4-year-old children, and pre-pregnancy BMI was correlated with various indicators of body composition in children.

[Real world study and its application in gastrointestinal stromal tumor].

Gastrointestinal stromal tumor (GIST) is a relatively rare type of gastrointestinal tract tumors. Thus, it is difficult to perform randomized controlled trials (RCTs) of GIST in a single center, which are often plagued by a small number of participants. Real world study (RWS) is a complement to the evidence derived from traditional RCT. Emerging sources of real world data offer enormous opportunity for deeper understanding of why treatments work (or not) and for whom. Evidence generated from RWD can help clarify best use of treatments for individuals and populations, and care value. Thus, RWS of GIST has attracted much attention. RWS helps us better understand the diagnosis, treatment, prognosis and outcome prediction of GIST in clinical practice. GIST is often misdiagnosed as other tumor. A diagnostic test provides evidence on how well a test correctly identifies or rules out GIST. Therapeutic research aims to evaluate the effectiveness and/or safety of a therapy for GIST. Prognostic research aims to forecast the likely outcome of GIST, explore the factors affecting the outcome, and analyze quality of life. Predictive research aims to quantify the probability of identification or health outcome of GIST based on a set of predictors. Pharmacoeconomic data in real world can evaluate the cost-effectiveness of medicinal products for GISTs and serve as a guidance tool for optimal healthcare resource allocation. Attaching importance to data sourse and data quality, strenthening communicate with a qualified statistician, and the implementation of a standardized process are necessary for performing a high-quality RWS.

Regulation of CO on heterocyst differentiation and nitrate uptake in the cyanobacterium Anabaena sp. PCC 7120.

AIMS: The aim of the present investigation was to study the effects of different inorganic carbon and nitrogen sources on nitrate uptake and heterocyst differentiation in the culture of cyanobacterium Anabaena sp. PCC 7120. METHODS AND RESULTS: Anabaena was cultivated in media BG11 containing combined nitrogen and supplementary NaHCO3 or CO2. Cell growth, heterocyst differentiation, nitrate reductase (NR, EC 1.7.7.2), glucose-6-phosphate dehydrogenase (G6PDH, EC 1.1.1.49) and NO uptake were analysed. The cells cultivated in BG11(0) medium with aeration were taken as reference. Experimental results showed that the differentiation frequency of heterocysts when the cells were cultivated with elevated CO2 was higher than that of the cells grown with air or bicarbonate. Heterocysts appeared unexpectedly when CO2 was introduced into the medium containing nitrate. However, no heterocysts emerged when CO2 was added to medium containing NH or urea, or when NaHCO3 was supplied to the medium with nitrate. Both nitrate uptake rate and nitrate reduction enzyme activity were depressed by the supplement of CO2 to the culture. The activity of G6PDH was enhanced with the increase in heterocyst differentiation frequency. CONCLUSION: CO2 might compete with NO for energy and electrons in the uptake process and CO2 appears favoured. This led to a high intracellular C/N ratio and a relative N limitation. So the process of heterocyst differentiation was activated to supplement nitrogen uptake. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provided an attractive possibility to form more heterocysts by rapid growth of Anabaena cells cultivated in the medium containing nitrate in order to increase nitrogen fixation and hydrogen production.

[Studies on the growth characteristics of Spirulina cells under batch and continuous conditions].

The research paper focused mainly on the growth characteristics of Spirulina cells under batch and continuous conditions. It was found that the Richards and Exponential decay model could well express the relationships between the concentration of the cell, carbon in the medium and culture time respectively. The maximum cell growth rate and the cell yield coefficient against carbon under batch culture was 0.371 g/d/L and 3.439 g/gC respectively. The concentration of cell and that of carbon in the reactor increased and decreased with the dilution rate respectively under the continuous culture condition. The maximum cell growth rate and the optimum dilution rate was 0.362 g/d/L and 0.45/d respectively. The cell yield against carbon under continuous culture condition was 2.050 g/gC. The cell growth rate of batch culture was larger than that of continuous one when the cell concentration was relatively low, but it will be smaller than that of continuous culture when the cell concentration became high.

[Culture medium optimization and primary kinetics analysis for nisin production].

Response surface methodology was used to optimize a medium for nisin production of Lactococcus lactis. In the first optimization step the influence of sucrose, soybean peptone, yeast extract, potassium dihydrogen phosphate, sodium chloride, and magnesium sulfur on nisin production was evaluated using a fractional factorial design. Potassium dihydrogen phosphate influenced nisin production positively while soybean peptone affected nisin production negatively. The other components had no significant effect on nisin production. The path of steepest ascent was used to approach the optimal region of the medium composition. In the third step the optimal concentrations of KH2PO4 and soybean peptone were determined by a central composite design and response surface analysis. The optimized medium allowed nisin production to be increased from 1074 IU/mL to 2150 IU/mL. The kinetic analysis showed that nisin production fashion at optimized and non-optimized media was not changed and maintained partially growth-associated. But the specific growth rates and the specific nisin production rates for the strain at the optimized medium were bigger than the ones at the non-optimized medium after the cells entered the middle of exponential phase.

[Photoautotrophic cultivation of Synechococcus sp. PCC7002 in photobioreactor].

The Photoautotrophic cultivation of Synechococcus sp. PCC 7002 in a 15 L-airlift photobioreactor was carried out. The changes of light intensity with cell density and optical length in the cultivation system were investigated. Based on experimental results, the light attenuation could be described by I = I0exp [-(-0.0239 + 0.0777 OD750).L]. The effects of the variations of light intensity, CO2 concentration in gas inlet and culture temperature on the growth of cells during the cultivation process have also been studied. The optimized condition was determined and a high dry cell density of 3.4 g/L was obtained. The volumetric productivity reached 0.57 g/(L.d) under the optimized condition.

Evaluation of the air bronchogram sign on CT in solitary pulmonary lesions.

PURPOSE: Our goal was to evaluate the presence and the significance of the air bronchogram sign in solitary pulmonary lesions (SPL) on CT. METHOD: One hundred thirty-two patients with SPL who underwent chest CT scans and had histological diagnosis were studied retrospectively. We reviewed all chest CT scans to assess for the presence of the air bronchogram sign in the SPL and recorded the distribution of this sign in malignant and benign lesions. The morphology of the aerated bronchi in the lesion and its significance in differential diagnosis were also evaluated. RESULTS: Of 17 cases of benign lesions, only 1 (5.9%) had an air bronchogram; of 115 lung cancers, 33 (28.7%) had this sign (p < 0.05). The encased bronchi exhibited four morphologic patterns: normal, tortuous, ectatic, and cut-off. The morphology of the bronchus in the benign lesion was normal. However, bronchi in malignant lesions displayed all four types of morphology. The air bronchogram sign was seen in all histologic types of lung cancer (squamous cell 10, adenocarcinoma 9, bronchioloalveolar cell 12, small cell 1, non-small cell 1). Lesions of different sizes were noted to have air bronchograms, including those < 2 cm in diameter. CONCLUSION: The CT air bronchogram sign in SPL is significantly more common in malignant than in benign lesions. The sign is seen in all lung cancer cell types and demonstrates varied bronchial morphology.

[MRI diagnosis of mediastinal tumors: a report of 20 cases].

With the use of MRI, 20 pathologically proved cases of mediastinal tumor were analysed, of which 13 cases were also studied with CT. Compared with CT, the three-dimensional morphological study of the lesions by MRI provided better evaluation of their location and of their characteristics. The abnormal signals on T1WI, PDWI and T2WI images, particularly of lipoma, fluid-contained cyst, lymphoma and cystic teratoma, were highly accurate in diagnosing mediastinal tumors; in addition, MRI was ideal for demonstrating the tumor capsule in neurogenic tumor or fibrous septa within the lipoma. Specific MRI findings facilitate the diagnosis of an aneurysm. Finally, the limitations of MRI were also discussed.

Structural diversity of the classical H-2 genes: K, D, and L.

Twenty-three class I DNA sequences, representing alleles of the H-2K, D, and L loci, were analyzed to assess patterns of nucleotide and amino acid diversity. Comparisons of the allelic and nonallelic sequences revealed locus specificity in regions encoding the leader peptides and the carboxyl-terminal segments of the Ag presenting molecules. Analyses focusing on the sequences that determine the Ag binding domains revealed weak or insignificant allelic associations, a finding that is in sharp contrast to previously observed relationships among the homologous human sequences. The amino acid positions exhibiting high diversity in the encoded glycoproteins in both mice and humans are localized primarily to the Ag binding site. In the mouse, diverse amino acids were positioned similarly in the K and D/L glycoproteins, although in humans, the A and B glycoproteins exhibit distinctive differences in their locations within the Ag binding site. The absence of locus specificity among the sequences that determine the Ag binding domains of the mouse is consistent with the hypothesis that ectopic gene conversion leads to interlocus exchange of class I sequences. Comparable interlocus exchanges among human class I genes have not played a similar role in shaping human A and B sequences. The basis of this difference between mice and humans is not clear. The nature of amino acid substitutions distinguishing class I loci in mice and humans are comparable, and the role of natural selection in determining diversity appears to be similar in the two species.

Structure and diversity of class I antigen presenting molecules in the mouse.

Sequence comparisons among class I genes provide insight into the nature and origins of diversity in the human and mouse MHC. The profiles of diversity among alleles and between different loci indicate that genetic interactions among class I genes generate sequence diversity in both species. Humans and mice differ in the extent that sequence transfer occurs between loci. In mice, sequences encoding the antigen binding domain show little evidence of locus specificity. A series of mouse class I mutants have been analyzed, providing strong evidence that interlocus gene conversion plays a significant role in the exchange of sequences among class I genes. A similar process is suspected in human class I and both mouse and human class II genes. However, the transfer of sequence among genes in these groups appears to occur predominantly between alleles and only to a minor extent between loci.

Gene splicing by overlap extension: tailor-made genes using the polymerase chain reaction.

Gene Splicing by Overlap Extension or "gene SOEing" is a PCR-based method of recombining DNA sequences without reliance on restriction sites and of directly generating mutated DNA fragments in vitro. By modifying the sequences incorporated into the 5'-ends of the primers, any pair of polymerase chain reaction products can be made to share a common sequence at one end. Under polymerase chain reaction conditions, the common sequence allows strands from two different fragments to hybridize to one another, forming an overlap. Extension of this overlap by DNA polymerase yields a recombinant molecule. This powerful and technically simple approach offers many advantages over conventional approaches for manipulating gene sequences.