Objective:To investigate the clinical and pathological features of pediatric NTRK-rearranged tumors.Methods:Four NTRK-rearranged soft tissue tumors and one renal tumor at Shanghai Children′s Medical Center, Shanghai Jiaotong University and Singapore KK Women′s and Children′s Hospital from January 2017 to September 2019 were identified. Pan-TRK immunohistochemistry, and the ALK and ETV6 gene break-apart fluorescence in situ hybridizations (FISH) were performed. NTRK gene rearrangement was detected using sequencing-based methods.Results:There were 3 males and 2 females in this study. The patients were between 3 months and 13 years of age. Histologically, the tumors were infiltrative spindle cell tumors with variable accompanying inflammatory cells. Immunohistochemistry showed positive reactivity for pan-TRK in all tumors, with nuclear staining for NTRK3 fusion, and cytoplasmic staining for NTRK1 fusion. The molecular testing revealed NTRK gene fusions (one each of TPM3-NTRK1, ETV6-NTRK3 and DCTN1-NTRK1, and two cases of LMNA-NTRK1). Two patients were receiving larotrectinib. The others were are well without disease, with follow-up durations of 9 to 29 months.Conclusions:NTRK-rearranged mesenchymal tumors from soft tissue sites and kidney are identified. A novel DCTN1-NTRK1 fusion is described. Pan-TRK immunohistochemistry is useful for diagnosis. NTRK-targeted therapy may be an option for unresectable, recurrent or metastatic cases.

In this study, rats were used to evaluate the effect of Radix glycyrrhiza on reducing liver toxicity of Tripterygium wilfordii. Metabonomics techniques were used to analyze the changes of small molecular metabolites and the metabolic pathways involved in the beneficial process. Different groups of rats were given for the extractions from Tripterygium wilfordii and Tripterygium wilfordii together with Radix glycyrrhiza. The general state, pathological changes of liver tissue, biochemical indexes of liver function and the changes of inflammatory factors in rats were observed. The results showed that the liver tissue injury of Tripterygium wilfordii group was significant, and the injury was reduced by Radix glycyrrhiza. Biochemical indexes and inflammatory factors also suggested that Tripterygium wilfordii together with Radix glycyrrhizaeffectively decreased the liver toxicity. HPLC-MS/MS-IT-TOF was used to characterize the difference of serum metabolism in rats. Multivariate statistical analysis was used to screen 15 potential biomarkers, such as fatty acid, glycerol ester, glycerol phosphate, phosphatidylethanolamine and phosphatidylcholine. It mainly involved in 7 metabolic pathways, such as glycerol phospholipid metabolism, linoleic acid metabolism, alpha linoleic acid metabolism, and glycosyl phosphatidylinositol terminal biosynthesis. The results showed that the Tripterygium wilfordii compatibility of Radix glycyrrhizaeffectively decreased the liver toxicity induced by Tripterygium wilfordii. Phospholipid metabolism may be the key metabolic pathway of Tripterygium wilfordii hepatotoxicity and the target of Radix glycyrrhiza. This study provides a reference for the control of liver toxicity of Tripterygium wilfordii.

According to different toxicities of various aqueous extracts of Polygonum multiflorum on hepatocyte, the impacts of chemical composition on the safety of P. multiforum was studied. In this study, 8 main chemical compositions in aqueous extracts of P. multiflorum were determined by the established HPLC method; at the same time, the inhibition ratios of different aqueous extracts of P. multiflorum on L02 cell were determined. Afterwards, the potential compounds related to the toxicity of P. multiforum were tentatively found through a multiple correlation analysis. The results showed that P. multiforum with different chemical compositions exhibited great differences in dissolution. The hepatocyte toxicity of P. multiflorum powder was much greater than P. multiflorum lumps. In addition, three constituents closely related to toxicity of P. multiflorum were found by multiple correlation analysis. The study revealed that chemical composition of P. multiflorum is closely related to the hepatotoxicity, and the hepatotoxicity of P. multiflorum powder is greater than that of other dosage forms. This study indicates that P. multiflorum with different chemical compositions show varying toxicity, which therefore shall be given high attention.

Objective To study the effect and mechanism of the dysfunction of CD4

Dietary pattern has been revealed to be associated with metabolic syndrome. However, the association was not well documented in Chinese due to the complexity of Chinese foods. We mainly assessed the dietary patterns and examined their effects on metabolic syndrome among Chinese adults. Four dietary patterns including 'Refined Grains & Vegetables' Pattern, 'Dairy & Eggs' Pattern, 'Organ Meat & Poultry' Pattern, and 'Coarse Grains & Beans' Pattern were extracted. 'Dairy & Eggs' Pattern was associated with a decreased odds of metabolic syndrome in women, and 'Coarse Grains & Beans' Pattern was associated with a decreased odds of hypertension in men. These results provided a scientific basis for future research and dietary guideline perfection.
Adult ; Aged ; Diet ; Feeding Behavior ; Female ; Food ; classification ; Humans ; Male ; Metabolic Syndrome ; epidemiology ; etiology ; Middle Aged

The study is to report the establishment of a method of screening the antitumor compounds based on the dynamic bio-response profile of cells to make up for the shortages of conventional end-point tests such as tedious operation and low sensitivity. Based on the principle of electric impedance of cells, the real-time cell electronic sensing (RT-CES) system was used to monitor the effect of epirubicin (EPI), cisplatinum (DDP) and carboplatin (CBP) on the growth of HepG2 cells, with the cell index (CI), half maximal inhibitory concentration (IC50) and detachment curve as evaluation indexes. Meanwhile, cell counting kit-8 (CCK-8) and microscopy were applied for verification. The results showed that CI curve could sensitively real-time profile the inhibitory effect of model drugs on HepG2 cells. The IC50 of EPI, DDP and CBP were 0.53 +/- 0.04, 9.79 +/- 0.26 and 597.00 +/- 3.79 microg x mL(-1), respectively. What's more, the significant differences of detachment curves of the three drugs indicated that their functional mechanisms might be different, this is consistent with the literature. The RT-CES system with non-invasive, label-free and real-time characteristics could be used to monitor the bio-response profile of the three drugs to HepG2 cells, allowing to qualitatively and quantitatively distinguish the antitumor activities of the three drugs, and could be a complementary method for the present screening of antitumor compounds.
Antineoplastic Agents ; pharmacology ; Biosensing Techniques ; methods ; Cell Count ; Cell Line, Tumor ; Cisplatin ; pharmacology ; Drug Screening Assays, Antitumor ; Electric Impedance ; Humans

This study aims at trying to establish a novel method of sterility test for injections based on biothermodynamics, in order to overcome the deficiencies of routine sterility tests such as long detecting cycle, low sensitivity and prone to misjudgments. A biothermodynamics method was adopted to rapidly detect the microorganism contamination of injections by monitoring the heat metabolism during the growth of microbe. The growth rate equal to or greater than zero and the heat power difference of P(i) and P(0) with three folds higher than the noise of baseline were chosen as indexes to study the heat change rule of microbe. In this way, the effectiveness of the new method to detect strains required by conventional sterility test or in injection samples was also investigated. Results showed that the Gram-positive bacteria, Gram-negative bacteria and fungi demanded by sterility testing methodology could be detected by biothermodynamics method within 10 hours, with the sensitivity lower than 100 CFU x mL(-1). Meanwhile, this method was successfully applied to the sterility test of Compound Yinchen injection (FFYC), Shuanghuanglian powder injection (SHL) and Compound Triamcinolone injection (TAND) which were sterilized with different degrees. Therefore, the biothermodynamics method, with advantages of fast detection and high sensitivity, could be a complementary solution for conventional sterility tests.
Anti-Inflammatory Agents ; administration & dosage ; chemistry ; Drug Contamination ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Fungi ; isolation & purification ; Gram-Negative Bacteria ; isolation & purification ; Gram-Positive Bacteria ; isolation & purification ; Hot Temperature ; Injections ; Microbiological Techniques ; methods ; Sensitivity and Specificity ; Sterilization ; Triamcinolone ; administration & dosage ; chemistry

The present study is to investigate the quality changes of ginseng stems and leaves before and after frost. The contents changes of ginsenoside, free amino acid, and total phenolic compounds, as well as DPPH radical scavenging effect before and after frost were measured. The content of 9 ginsenoside monomer in ginseng stems was decreased except for Rg, and Re after frost, but in ginseng leaves was all decreased. The total content of amino acids was decreased in ginseng stems after frost, while increased in ginseng leaves. The content of phenolic compounds in ginseng stems and leaves were both decreased after frost while the ability of DPPH radical scavenging was improved. The factor of frost has great impact on the quality of ginseng stems and leaves.
Drugs, Chinese Herbal ; chemistry ; Ecosystem ; Freezing ; Panax ; chemistry ; Plant Leaves ; chemistry ; Plant Stems ; chemistry ; Quality Control

In vitro neuraminidase inhibition assays and ultrafiltration liquid chromatography with diodearray detector coupled to time of flight mass spectrometer (UPLC-DAD-TOF-MS) were combined to screen bioactive compounds inhibiting neuraminidase from Isatidis Radix. By comparing the compounds from Isatidis Radix before and after ultrafiltration, we found that arginine, goitrin and adenosinea can bind with neuraminidase, and the binding degree of the three compounds were (36.23 +/- 1.12)%, (32.54 +/- 1.02)% and (9.38 +/- 0.47)%, respectively. The IC50 of arginine and goitrin were (1.16 +/- 0.02), (1.20 +/- 0.02) g x L(-1), respectively. While the IC50 of adenosinea was higher than 500 g x L(-1). The results showed that arginine and goitrin might be the main compounds with antiviral activity of Isatidis Radix. This study may provide a useful method for the screening of bioactive compounds and quality control of Isatidis Radix.
Antiviral Agents ; analysis ; pharmacology ; Arginine ; analysis ; pharmacology ; Drug Evaluation, Preclinical ; Drugs, Chinese Herbal ; analysis ; pharmacology ; Isatis ; chemistry ; Mass Spectrometry ; Neuraminidase ; antagonists & inhibitors ; metabolism ; Orthomyxoviridae ; drug effects ; enzymology ; Oxazolidinones ; analysis ; pharmacology ; Plant Roots ; chemistry ; Ultrafiltration ; Viral Proteins ; antagonists & inhibitors ; metabolism

AIM: To investigate the cytotoxic effects of the six protoberberine alkaloids (PAs) from Rhizoma Coptidis on HepG2 cells. METHOD: A systematic screening was conducted to investigate the dynamic response of HepG2 cells to the PAs using the impedance-based xCELLigence system. Cisplatin was selected as the positive control. The real time, concentration-response curves and the 50% inhibitory concentrations (IC50) were acquired to evaluate the anticancer activity of the PAs. RESULTS: All of the six PAs inhibited cell growth and induce death in HepG2 cells in a time- and concentration-dependent manner. The IC50 values of cisplatin, berberine, columbamine, coptisine, epiberberine, jatrorrhizine, and palmatine were 5.13, 42.33, 226.54, 36.90, 302.72, 383.54, and 456.96 μg·mL(-1), respectively. The results obtained using the xCELLigence system corresponded well with those of the conventional methods. CONCLUSION The xCELLigence system is a reliable and efficient tool for real-time screening of the cytotoxic effect of compounds in cell-based in vitro assays. Coptisine and berberine, with methylenedioxy group at C2 and C3 on the phenyl ring showed stronger effect.than the other four PAs. However, compared with cisplatin, the six PAs didn't show obvious cytotoxic effect on HepG2 cells. These results provided some useful data for the evaluation of the anticancer compounds, and the clinical application of traditional Chinese medicine.
Antineoplastic Agents, Phytogenic ; pharmacology ; therapeutic use ; Berberine ; analogs & derivatives ; pharmacology ; therapeutic use ; Berberine Alkaloids ; pharmacology ; therapeutic use ; Cell Death ; drug effects ; Cisplatin ; pharmacology ; therapeutic use ; Coptis ; chemistry ; Drug Evaluation, Preclinical ; methods ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Electric Impedance ; Hep G2 Cells ; Hepatoblastoma ; drug therapy ; physiopathology ; Humans ; Inhibitory Concentration 50 ; Liver Neoplasms ; drug therapy ; physiopathology ; Phytotherapy ; Rhizome ; chemistry