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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.
Subject(s)
Humans , Gastrointestinal Stromal Tumors/genetics , Gene Fusion , Neoplasms , Nerve Growth Factors , Protein Kinase Inhibitors , Receptor, trkA/genetics , Receptors, Nerve Growth Factor/geneticsABSTRACT
OBJECTIVE: To evaluate the effectiveness of endoscopic submucosal dissection(ESD) in treating colorectal polyps with diameter≥2.5 cm. METHODS: The clinical data of 567 cases of colorectal polyps with diameter≥2.5 cmtreated by ESD at Endoscopy Center,Zhongshan Hospital,Fudan University between January 2007 and November 2016 were analyzed retrospectively. The data included clinical and pathological characteristics, complications and follow-up.RESULTS: Of all lesions, the median diameter was 3.0 cm(2.5 to 15.0). Among them, 448 lesions(79.0%)were high grade intraepithelial neoplasia, and the other 119 lesions(21.0%)were intra-adenoma adenocarcinoma, focal cancerization or adenocarcinoma. The complete resection rate during operation was 99.1%(562/567). The en bloc resection rate was 78.3%(444/567), and the curative resection rate was 90.8%(515/567). Additional surgeries or endoscopic treatment were performed in 31 cases after ESD treatment. Postoperative bleeding occurred in 3.7%(21/567) of all cases. Penetration and electrocoagulation syndrome after ESD occurred in 1.2%(7/567) and 5.3%(30/567) of casesrespectively. The median length of follow-up was 40(12-90) months, with a local recurrence rate of 1.1%(6/536). Intraoperative complications were related to lesions ≥5.0 cm(P<0.001) and non-en bloc resection(P=0.034).Electrocoagulation syndrome was related to lesions ≥5.0 cm(P=0.004). Postponed bleeding after ESD was related to hypertension (P=0.008). Local recurrence was related to lesions ≥5.0 cm (P=0.037). CONCLUSION: Treating colorectal polyps ≥2.5 cm with ESD is safeand feasible, resulting in high rate of curative resection and an extremely low local-recurrencerate. However, polyps≥5.0 cm showld be cautionly evaluated before ESD.
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Objective: To observe the effect of modified Chaihu Shugantang on the expression of miRNA-204 in hippocampus of epileptic mice, and to explore its mechanism of neuroprotection. Method: The sixty mice were randomly divided into 6 groups:normal group, model group (pilocarpine 180 mg·kg-1), and modified Chaihu Shugantang group (7 g·kg-1·d-1), modified Chaihu Shugantang+miRNA-204 mimic group (7 g·kg-1·d-1+ 2 μL), modified Chaihu Shugantang+miRNA-204 inhibitor group (7 g·kg-1·d-1+2 μL), carbamazepine group (30 mg·kg-1·d-1),each was given intragastric administration for 2 weeks,using pilocarpine to cause epilepsy in mice, respectively, add flavor to Bupleurum after intragastric administration, inhibition and overexpression of miRNA-204, the mice were sacrificed and their hippocampus tissues were harvested.The indicators of each group were observed, Real-time quantitative PCR detecting system (Real-time PCR) was used to detect mouse hippocampal miRNA-204 expression, Western blot analysis of autophagy-related protein microtubule-associated protein light chain 3 (LC3), autophagy-associated marker protein 7 (ATG7) expression, hematoxylin pathological condition of hippocampus in each group was observed by hematoxylin-eosin(HE)staining.The autophagy of hippocampus in each group was observed by transmission electron microscopy. Result: Compared with normal group, the expression of miRNA-204 was significantly decreased in model group (P(P(PPPPPConclusion: Modified Chaihu Shugantang can improve the pathological changes of hippocampus in mice with epilepsy and play a neuroprotective role. The mechanism may be to increase the expression of miRNA-204 in hippocampus of mice with epilepsy, inhibit excessive autophagy of neurons and reduce apoptosis.
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Both the increasing prevalence and growing burden of diabetes mellitus have caused global public health concerns.With the development of bio-psycho-social medical model,the impact of psychosocial factors on diabetes has attracted more attentions among the researchers.This paper summarizes findings from epidemiological studies that focusing on the association between diabetes and related psychosocial risk factors.Foreign studies have shown that psychological factors are closely related to diabetes,but the conclusions on social factors are inconsistent.Domestic studies have only targeted on small-sample-sized and cross-sectional studies.More longitudinal research is needed to confirm the impact of psychosocial factors on the risk of diabetes.
ABSTRACT
Both the increasing prevalence and growing burden of diabetes mellitus have caused global public health concerns.With the development of bio-psycho-social medical model,the impact of psychosocial factors on diabetes has attracted more attentions among the researchers.This paper summarizes findings from epidemiological studies that focusing on the association between diabetes and related psychosocial risk factors.Foreign studies have shown that psychological factors are closely related to diabetes,but the conclusions on social factors are inconsistent.Domestic studies have only targeted on small-sample-sized and cross-sectional studies.More longitudinal research is needed to confirm the impact of psychosocial factors on the risk of diabetes.
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The morbility of depression in epilepsy patients is relatively high,and children and adolescents are the main population of epilepsy.Because of the specific physical and mental development in children and adolescents,the incidence and medication in these population have their own characteristics.This paper reviews the research progress of the effects,causes,features,and interventions of epilepsy combined with depression in children and adolescents.
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Comorbid depression and chronic pain are highly prevalent in individuals suffering from physical illness .Here, we critically examine that inflammation is the possible mechanism of comorbidity of pain and depression .These mechanisms include direct effects of cytokines on the neuronal environment or indirect effects via downregulation of G protein -coupled receptor kinase 2, activation of the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase that generates toxic kynurenine metabolites .We review the role of in-flammation in the mechanism of the commorbidity of depression and pain .
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Objective 4-Hydroxyisoleucine (4-HIL) is the active component isolated from the seeds of Trigonella foenum-graecum. It exerts broad pharmacological effects such as anti-hyperglycemia,blood lipid lowing,improvement of insulin resistance,etc. As the Chinese traditional medicine,it can be used clinically in treating many diseases such as type 2 diabetes mellitus,dyslipidemia,metabolic syndrome,fatty liver and other diseases. Here the current research status and application prospect on 4-Hydroxyisoleucine were summarized.
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<p><b>OBJECTIVE</b>To explore the inhibitory effect of combined administration of bear bile powder (BBP) and cyclophosphamide (Cytoxan, CTX) on colorectal cancer liver metastasis by regulating tumor promotion inflammation microenvironment.</p><p><b>METHOD</b>The CRC liver metastasis mode in mice was established through in situ spleenic injection of SL4 tumor cells into spleens. The mice were randomly divided into 5 groups: the model group, the CTX (80 mg x kg(-1)) treatment group, the CTX + BBP high dose (300 mg x kg(-1)) group, the CTX + BBP middle dose (150 mg x kg(-1)) group and the CTX + BBP low dose (75 mg x kg(-1)) group. Mice were orally administered with drugs for 12 days, and sacrificed on the 13'h day for weighing their spleens and lives, HE staining, and immunofluorescence analysis. Their peripheral blood, and metastatic tumor in spleens and lives were analyzed with flow cytometry.</p><p><b>RESULT</b>Spleen and liver weights of the: CTX treatment group and other doses groups were significantly lower than that of the model group. HE staining and immunofluorescence analysis showed that lymphocyte infiltration was detected in normal tissues, and macrophages infiltration was observed around the tumor tissues. Flow cytometry analysis showed that the number of T-lymphocytes in peripheral blood of different doses groups were much higher than that of the CTX treatment group (P < 0.05), with the rise in the ratio of CD4/CD8; the total number of lymphocytes in spleen cell suspension increased in different doses groups, compared to the CTX treatment group, with notable increase in B cells (P < 0.05) and significant decrease in CD11b, F4/80 cells (P < 0.05). The combined treatment showed less monocyte macrophages in liver metastasis than that of the CTX treatment group.</p><p><b>CONCLUSION</b>The combined treatment of bear bile powder and cyclophosphamide has the effect in not only protecting liver and increase immunity, but also in anti-inflammation and antitumor by regulating tumor microenvironment and reducing the collection of mononuclear macrophages. Particularly, the combined administration of low dose of bear bile powder and CTX shows the most significant effect in reducing inflammatory cell infiltration.</p>
Subject(s)
Animals , Humans , Male , Mice , Bile , Chemistry , Colorectal Neoplasms , Drug Therapy , Mortality , Pathology , Combined Modality Therapy , Cyclophosphamide , Liver Neoplasms , Drug Therapy , Mortality , Mice, Inbred C57BL , Tumor Microenvironment , UrsidaeABSTRACT
This study was purposed to investigate the efficacy of different whole flow lysis reagents for lysis of red blood cells in flow cytometric analysis. The expression of immunocytes was detected by flow cytometry after lysis of red blood cells using commercial reagents (Optilyse C, FACS Lysing Solution) and self-made red blood cell lysis reagents (RBC Lysis Buffer), the detection results were analyzed comparatively. The results showed that there was no significant difference in the percentage of CD3e(+), CD3e(+)CD4(+), CD3e(+)CD8a(+), CD3e(-)CD19(+), CD3e(-)NK1.1(+) and Gr-1(+) cells between 3 different lysis reagent groups. However OptiLyse C solution was suitable to Gr-1(+) cell detection, but did not suit to Foxp3(+) Treg detection. The self-made RBC Lysis Buffer and FACS Lysing Solution were suited to Foxp3(+) Treg detection. It is concluded that the use of self-made RBC Lysis Buffer for flow cytometry can get the lysis efficiency of commercially available lysis solutions when samples are prepared in accordance with standardized procedure. The self-made RBC Lysis Buffer not only can satisfy experimental requirements, but also can reduce the experimental costs.
Subject(s)
Animals , Mice , Erythrocyte Count , Erythrocytes , Allergy and Immunology , Metabolism , Flow Cytometry , Methods , Immune System , Allergy and Immunology , Indicators and Reagents , Mice, Inbred C57BLABSTRACT
<p><b>OBJECTIVE</b>Functional defects in NK cells have been proposed to be responsible for the impairment of anti-tumor immune responses. However, it remained unclear whether the function of NK cells were impaired in patients with hepatocellular carcinoma. To address this issue, we analyzed the frequency and function of peripheral NK cell subsets in hepatocellular carcinoma (HCC) patients.</p><p><b>METHODS</b>35 HCC patients and 24 healthy controls (HC) were enrolled in the study. Peripheral NK frequency was analyzed using flow cytometry. In addition, the capacity of NK cells to produce IFN gamma and to lyse K562 cells was evaluated.</p><p><b>RESULTS</b>In contrast with the healthy controls, the frequency of peripheral NK cells in hepatocellular carcinoma patients was decreased (12.19%+/-10.85% vs 24.01%+/-8.78%, u = 4.01, probability value less than 0.01), while the frequency of CD56(bright)CD16(neg) NK cells was increased (0.62%+/-0.39% vs 0.48%+/-0.28%, u = 1.96, probability value less than 0.05), and the frequency of CD56(dim)CD16(pos) NK cells was significantly decreased (11.59%+/-7.49% vs 22.66%+/-8.84%, u = 3.92, probability value less than 0.01). In addition, peripheral NK cells from HCC patients exhibited decreased capacity to produce IFN gamma (effective cells 13.31%) and to lyse K562 cells (mixed ratio 30:1, 10:1, 1:1, effective cells 16.72%+/-7.33% vs 26.29%+/-12.36%, u = 2.52, P less than 0.05, 8.01%+/-4.40% vs 13.09%+/-5.03%, u = 3.32, probability value less than 0.05, 3.51%+/-2.82% vs 3.42%+/-1.64%, u = 1.56, probability value more than 0.05, respectively) as compared with healthy subjects.</p><p><b>CONCLUSION</b>Anti-tumor activity of NK cells in HCC patients was impaired.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , CD56 Antigen , Allergy and Immunology , Carcinoma, Hepatocellular , Allergy and Immunology , Case-Control Studies , Cytotoxicity Tests, Immunologic , Cytotoxicity, Immunologic , Flow Cytometry , Interferon-gamma , Metabolism , K562 Cells , Killer Cells, Natural , Allergy and Immunology , Liver Neoplasms , Allergy and Immunology , Lymphocyte Subsets , Allergy and Immunology , Receptors, IgG , Allergy and ImmunologyABSTRACT
The United Nations Environment Program estimates that approximately 20% of agricultural land and 50% of cropland in the world is salt-stressed. The gene NHX (Na+/H+ exchanger) encodes functional protein that catalyzes the countertransport of Na+ and H+ across membranes and may play an important role in plant salt tolerance. To clone the NHX from the wild plant Populus euphratica collected in Tarim basin and Xinjiang Wujiaqu district into a T-vector, designed primer was used to amplify 1kb NHX cDNA fragment with RT-PCR. Total RNA was extracted from Populus euphratica tissue (plant tissue was collected from Tarim basin and Xinjiang Wujiaqu district and stored in liquid nitrogen) according to the Plant RNA Mini Kits of Omega. First cDNAs were synthesized from 1 microg total RNA of Populus euphratica seedling. A pair of primers were used to perform RT-PCR. The amplified DNA fragment was purified and cloned into pMD18-T vector. However, 1kb and 2.3kb fragment were obtained from Tarim basin and Xinjiang Wujiaqu district and named as PtNHX and PwNHX, respectively. Sequence analysis reveals that the cloned PtNHX fragment of Populus euphratica contains partial NHX coding region with 98%, 86%, 84% and 80% identity comparing with Atriplex gemelini, Suaeda maritima, Arabidopsis thaliana and Oryza sativa, respectively. This analysis suggests that NHX gene would be highly conserved in terms of evolution in plant; and it also suggests that the NHX gene of Populus euphratica also would have the similarity with that of Arabidopsis. It may be of great importance in improvement of the plant salt tolerance and breed of crop. At the same time, sequence analysis shows that PwNHX gene includes a coding region about 1350bp with 99% identity comparing with transposon Tn10 IS10-left transposase of Shigella flexneri. On the one hand, the NHX gene may lose its function because it was inserted a fragment in coding region. On the other hand, its product may play a important role in salt tolerance. Populus grow in saline soil. It speculates that it may have other salt tolerance mechanism in Populus. The transposon can be used as transposon tagging to clone other genes and it will help us to understand farther the salt tolerance mechanism.