[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.

[Large nested variant of urothelial carcinoma of urinary bladder: a clinicopathological analysis of five cases].

Objective: To investigate the clinicopathologic features, diagnosis and differential diagnosis of large nested variant of urothelial carcinoma (LNUC) of urinary bladder. Methods: The clinical and pathologic data of five cases of LNUC of urinary bladder diagnosed between January 2014 and December 2018 at the Department of Pathology, Zhejiang Provincial People's Hospital were analyzed by immunohistochemistry (IHC) and Sanger sequencing. The relevant literature was reviewed. Results: All five patients were male with a mean age of 63 years (range, 48 to 81 years). The mean tumor size was 3.4 cm (range, 1.7 to 4.7 cm). Histologically, the invasive LNUC tumor cells formed medium to large sized nests of varying shapes, from regular round, bulbous, oval to irregularly fused, branched, dumbbell shaped glands, with mild stromal reaction. In all five cases, focal central necrosis and microcystic changes in the tumor nests were identified. Cytologically, the tumor cells were low grade in four cases; the remaining case was overall low grade with focal high grade areas. Mitoses were scarce. All cases possessed surface urothelial tumors, including three low-grade papillary carcinomas, one high-grade papillary carcinoma and one carcinoma in situ. Three of the LNUC were accompanied by small nested variant of urothelial carcinoma and two by conventional high grade invasive urothelial carcinoma. Perineural involvement and angiolymphatic invasion were each noted in four tumors. Radical cystectomy was performed in four cases with TNM stages as followings: pT3aN0M0 in two cases, pT4aN0M0 and pT4aN1M0 in one case each. The remaining case had transurethral bladder resection and was of pT2 stage. By IHC, all five cases were positive for CK7 and p40; four were positive for GATA3; two were positive for CK20; and the mean Ki-67 proliferation index was 18%. TERT promoter mutation status were successfully performed in three cases, with one showing mutation (C228T) and two were wild type. All patients received postoperative chemotherapy. At a follow-up of 2 to 11 months, one patient died of unrelated causes, two patients developed metastases, and two were alive with no evidence of disease. Conclusions: LNUC is a histologic subtype of urothelial carcinoma with deceptively benign features but aggressive behavior, and appreciation of its unique infiltration patterns can aid in diagnosis and differential diagnosis. LNUC tends to coexist with small nested variant of urothelial carcinoma, suggesting these may represent different manifestations of the same urothelial carcinoma subtype.

Effect of miR-29c on renal fibrosis in diabetic rats via the AMPK/mTOR signaling pathway.

OBJECTIVE: To explore the effect of micro-ribonucleic acid (miR)-29c on renal fibrosis in diabetic rats through the adenosine 5'-monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway, and to investigate its related mechanism by the research on the effect of miR-29c on the expression of fibrosis-related genes. MATERIALS AND METHODS: The rat model of diabetic nephropathy (DN) was established, and the levels of fasting blood glucose (FBG), 24 h urine protein (24h-Pro), blood urea nitrogen (BUN), and serum creatinine (sCr) were monitored. After the rats were executed, kidney tissues were dissected, stained with paraffin and embedded in hematoxylin and eosin (H&E). Then, Western blotting was used to detect the levels of miR-29c, phosphorylated-AMPK (p-AMPK), α-smooth muscle actin (α-SMA), tumor necrosis factor-α (TNF-α), and macrophage migration inhibitory factor (MIF). The human renal tubular epithelial HK-2 cell line was treated with high glucose (HG) to simulate DN cell status in vivo. After that, the expressions of miR-29c and the renal fibrosis marker α-SMA were examined via Western blotting. Finally, the level of α-SMA was measured by Western blotting after HG treatment combined with miR-29c silencing. RESULTS: The levels of FBG, BUN, sCr, and 24h-Pro in DN model rats were significantly higher than those in rats of control group. The data manifested that the DN model was successfully established. The expression level of miR-29c in DN model rats was markedly increased and that of the downstream protein p-AMPK also exhibited a significantly increasing trend. In addition, the levels of α-SMA, TNF-α, and MIF were elevated. The expression levels of miR-29c and α-SMA were increased markedly after the human renal tubular epithelial HK-2 cell line was treated with HG, but the expression of α-SMA was reduced after HG treatment combined with miR-29c silencing for 24 h. CONCLUSIONS: MiR-29c is probably related to the occurrence and development of DN. Besides, miR-29c silencing may inhibit the DN renal fibrosis through AMPK/mTOR signals, so miR-29c may be an effective target for the treatment of DN renal fibrosis.

Enhanced glycolysis in the process of renal fibrosis aggravated the development of chronic kidney disease.

OBJECTIVE: To explore the effect of glycometabolism on renal fibrosis and its underlying mechanism. MATERIALS AND METHODS: For in vivo experiments, unilateral ureteral obstruction (UUO) mouse model was constructed to induce renal interstitial fibrosis. Fibrosis and proliferation indicators in renal tissues were detected to observe the fibroblast phenotype changes during the process of renal fibrosis. Moreover, mRNA and protein levels of key enzymes in glycometabolism were also detected. For in vitro experiments, plasmid transfection was performed to overexpress pyruvate kinase M2 (PKM2) to explore the relationship between PKM2 and renal interstitial fibrosis. Energy metabolism monitoring was performed to detect changes in aerobic glycolysis and oxidative phosphorylation during the process of TGF-ß1-induced fibroblast phenotype changes. RESULTS: Fibroblast phenotype was changed. Both fibrosis and proliferation indicators were upregulated during renal fibrosis. Meanwhile, elevated expressions of key enzymes in glycometabolism and metabolic reprogramming of fibroblasts were observed. Overexpressed PKM2 activated fibroblasts and induced renal interstitial fibrosis, accompanied by increased glycometabolism level. CONCLUSIONS: Metabolic reprogramming promoted renal interstitial fibrosis, which leads to alteration of cell energy metabolism model.

[Interaction between passive smoking and folic acid supplement during pregnancy on autism spectrum disorder behaviors in children aged 3 years].

OBJECTIVE: To explore the interaction between passive smoking and folic acid supplement during pregnancy on children autism spectrum disorder(ASD)behaviors. METHODS: Children aged about 3 years were enrolled at kindergarten entrance in Longhua district of Shenzhen in 2014. Self-administered questionnaires were completed by their primary caregivers and the information about children' s age, gender, history of preterm birth and low birth weight, parents' education level, parents' reproductive age and family income were collected. The children ASD behaviors were assessed with Autism Behavior Checklist(ABC). According to the cut point of ABC, the children were divided into normal group with score less than 31, sub-clinical group with score ranging from 31 to 61 and suspect clinical group with score no less than 62. After controlling for potential confounders, multivariate logistic regression analysis was performed to evaluate the main effects and the interaction between passive smoking and folic acid supplement during pregnancy on children ASD behaviors. RESULTS: Maternal passive smoking during pregnancy was significantly associated with children ASD behaviors(sub-clinical group: OR=1.48; suspect clinical group: OR= 2.85), and maternal folic acid supplement during pregnancy was not related to children ASD behaviors(sub-clinical group: OR=1.04; suspect clinical group: OR=0.75). Stratified analysis showed that folic acid supplement during pregnancy was negatively associated with children ASD behaviors(suspect clinical group: OR=0.30)among children without mothers' passive smoking during pregnancy, and that mothers' passive smoking during pregnancy was positively associated with children ASD behaviors(sub-clinical group: OR=1.52; suspect clinical group: OR=4.45)among the children whose mothers had folic acid supplement during pregnancy. Furthermore, an interaction effect on children ASD behaviors was found between passive smoking and folic acid supplement during pregnancy(suspect clinical group: OR=5.30). CONCLUSION: Passive smoking and folic acid supplement during pregnancy were related to children ASD behaviors and had an interaction on children ASD behaviors.

Superchirped moiré grating based on an acousto-optic superlattice with a chirped fiber Bragg grating.

A superchirped moiré grating has multiple superimposed chirped Bragg gratings. We show that a superchirped moiré grating can be formed in an acousto-optic superlattice with a chirped fiber Bragg grating. There are multiple transmission peaks related to Fabry-Perot resonance in the transmission spectrum. The peak spacing is varied by the acoustic frequency. The proposed devices can be used as tunable multiple-passband transmission filters and switches.

Microcapsules through polymer complexation. I: Complex coacervation of polymers containing a high charge density.

Acidic and basic methacrylate co- and ter-polymers based on (respectively) methacrylic acid (MAA) and dimethylaminoethyl methacrylate (DMAEMA) were prepared by solution free radical polymerization and structurally characterized by NMR spectroscopy and dilute solution viscometry. Relationships between pKa/pKb/pH, solubility and extent of ionization were determined by acid/base titration. Yields and equilibrium water contents of complex coacervates from these polymers were measured, and microcapsule forming systems based on this effect were developed as potential prostheses for organ transplantation. Short term cell viability in these capsules was demonstrated using erythrocytes as a model cell line.

Kashin-Beck disease: a cross-sectional study in seven villages in the People's Republic of China.

Kashin-Beck disease (KBD) is an endemic disease that occurs in certain parts of the People's Republic of China and in Russia. The etiology of the disease is unknown. Selenium deficiency, mycotoxins, and chelating agents such as humic acid and decaying plant material from walnut tree forests have been suggested as causal agents. The primary lesion of this disease is the selective coagulative necrosis of the hypertrophic chondrocytes at the base of the articular and growth plate cartilages. A cross-sectional study was performed in the People's Republic of China in 7 villages, to focus on information about life styles, food consumption, and environmental factors from the village population where the disease is endemic. A total of 425 children were examined, of which 71 children had KBD. Results of detailed food consumption data analyses showed that certain combinations of food substances high in protein had a protective effect. It was also found that the disease was twice as prevalent in onset in boys as in girls, in the 12-yr-old age group. The overall onset of illness in this group of children ranged from 4 to 13 yr. Either the joints of the fingers or one ankle was affected first. Many of these children also had discolored teeth. However, this finding was unrelated to KBD.