Objective:To explore the cause of inconsistency between the results of trisomy 7 by expanded non-invasive prenatal testing (NIPT-PLUS) and trisomy 18 by prenatal diagnosis.Methods:A pregnant woman who received genetic counseling at Jiaozuo Maternal and Child Health Care Hospital on July 5, 2020 was selected as the study subject. NIPT-PLUS, systematic ultrasound and interventional prenatal testing were carried out. The middle segment and root of umbilical cord, center and edge of the maternal and fatal surface of the placenta were sampled for the validation by copy number variation sequencing (CNV-seq).Results:The result of NIPT-PLUS indicated that the fetus has trisomy 7. Systematic ultrasound has shown multiple malformations including atrioventricular septal defect, horseshoe kidney, and rocker-bottom feet. However, QF-PCR, chromosomal karyotyping analysis, and CNV-seq of amniotic fluid samples all showed that the fetus was trisomy 18. Validation using multiple placental samples confirmed that the middle segment of the umbilical cord contains trisomy 18, the center of the placenta contained trisomy 7, and other placental sites were mosaicism for trisomy 7 and trisomy 18. Notably, the ratio of trisomy 18 became lower further away from the umbilical cord.Conclusion:The false positive results of trisomy 7 and false negative trisomy 18 by NIPT-PLUS was probably due to the existence of placental mosaicism. Strict prenatal diagnosis is required needed aneuploidy is detected by NIPT-PLUS to exclude the influence of placental mosaicisms.

OBJECTIVE To study the effect and potential mechanism of eriodictyol on non-alcoholic fatty liver disease （NAFLD）. METHODS Sixteen C57BL/6J mice were randomly divided into control group， NAFLD model group， and eriodictyol low-dose and high-dose groups （50， 100 mg/kg）， with 4 mice in each group. Except for control group， the other groups were fed with high fat diet to induce NAFLD model. After four weeks of preprocessing， they were given relevant medicine intraperitoneally （0.01 mL/g）， once a day， for 6 consecutive weeks. The body weight and liver weight of mice were measured， and the pathological damage of liver tissue in mice was observed. The levels of aspartate aminotransferase （AST）， alanine aminotransferase（ALT）， and triglycerides （TG） in serum， as well as the protein expressions of nuclear factor-erythroid 2-related factor 2 （Nrf2） and heme oxygenase-1 （HO-1） in liver tissue were determined. In vitro NAFLD model was established by using 0.5 mmol/L oleic acid （OA） in HepG2 cells. Normal control group， NAFLD model group and eriodictyol low-， medium- and high-concentration groups （50， 100， 150 μmol/L） were set up. HepG2 cells in drug groups were treated with eriodictyol for 24 h at the time of modeling. The lipid deposition was observed in cells， and the levels of TG， malondialdehyde （MDA） and reactive oxygen species （ROS） as well as the phosphorylation levels of the mitogen-activated protein kinase （MAPK） signal pathway related proteins [extracellular signal-regulated kinase （ERK）， c- Jun N-terminal kinase （JNK）] and the protein expressions of Nrf2 and HO-1 were all determined. RESULTS In the in vivo experiment， compared with the NAFLD model group， the body weight， liver weight， the serum levels of AST， ALT and TG were all decreased significantly in eriodictyol low- and high-dose groups （except for serum level of AST in eriodictyol low-dose group） （P＜0.01）； liver lipid deposition was reduced significantly and the protein expressions of Nrf2 and HO-1 in liver tissues were further up-regulated （P＜0.01）. In the in vitro experiment， compared with the NAFLD model group， the lipid deposition in hepatocytes was reduced in eriodictyol low-， medium- and high-concentration groups （P＜0.01）， and the levels of ROS， MDA and TG were down-regulated （P＜0.05 or P＜0.01）； the phosphorylation levels of ERK and JNK were significantly down-regulated （P＜0.01）， while the protein expressions of Nrf2 and HO-1 were up-regulated significantly （P＜0.01）. CONCLUSIONS Eriodictyol can inhibit MAPK signaling pathway and activate Nrf2/HO-1 signaling pathway to alleviate NAFLD.

Malignant tumor poses a threat to human health and life. The incidence and fatality rate of malignant tumor have been on the rise. The currently available therapies are radiotherapy and chemotherapy， which cause severe adverse reactions and irreversible damage and thus influence the quality of life of patients. Therefore， it is urgent to find new， safe and effective antitumor drugs. Chinese medicinals are safe with little adverse reactions and long-lasting effect in the treatment of tumor， which have attracted the attention of scholars. Amid the advancement of medical research， more and more anti-tumor components have been extracted from Chinese medicinals. Phellinus is a valuable Chinese medicinal material， and the chemical components mainly include polysaccharides， flavonoids， triterpenes， and polyphenols， which have anti-inflammatory， hypoglycemic， liver-protecting， and anti-tumor effect. The chemical components of Phellinus can inhibit various malignant tumors such as lung cancer， gastric cancer， colon cancer， and melanoma. It exerts the anti-tumor effect by inhibiting proliferation and metastasis of tumor cells， inducing apoptosis and autophagy of the cells， suppressing tumor angiogenesis， and regulating the immunity. In addition， it can enhance efficacy， reduce toxicity， and boost the sensitivity in the radiotherapy and chemotherapy. In this paper， articles were retrieved from China National Knowledge Infrastructure （CNKI）， Web of Science， Pubmed， and Google Scholar with keywords such as "Phellinus， chemical components， and anti-tumor"， and then the chemical components of Phellinus and the anti-tumor mechanisms were summarized. The findings are expected to lays a basis for further development and clinical application of this medicinal.

Objective:To observe the effect of bacteroides fragilis BF839 intervention on learning, memory and social novelty of fragile X-mental retardation gene 1 ( Fmr1) knockout (KO) mice. Methods:Thirty three-week-old Fmr1 KO mice were randomly divided into Fmr1 KO group ( n=15) and Fmr1 KO+BF839 group ( n=15). Mice in the Fmr1 KO group freely drank autoclaved tap water everyday; mice in the Fmr1 KO+BF839 group drank BF839 bacterial liquid (10 mL/d) everyday;11 wild-type mice freely drank autoclaved tap water everyday were set as controls (WT group). After 4 weeks of intervention, Morris water maze test was used to observe the differences in escape latency and frequencies of crossing the original platform among mice in each group; Three-chamber Social Interaction Test was used to observe the differences in contact frequencies and contact durations with unfamiliar mice among mice in each group. Results:On the 4 th d of experiment, the escape latency of mice in the Fmr1 KO group ([46.06±10.29] s) was significantly longer than that in the WT group ([33.39±12.02] s, P<0.05); the escape latency of mice in the Fmr1 KO+BF839 group ([28.39±9.07] s) was significantly shorter than that in the Fmr1 KO group ( P<0.05); the escape latency of mice in the Fmr1 KO+BF839 group was slightly shorter than that in the WT group without significant difference ( P>0.05). The frequencies of crossing through the original platform of mice in Fmr1 KO group (0.00[0.00, 1.00] time) was slightly less than that in WT group (1.00 [0.00, 1.00] time) without significant difference ( P>0.05); that in the Fmr1 KO+BF839 group (1.50[1.00, 2.00] times) was significantly larger than that in the Fmr1 KO group and WT group ( P<0.05). The contact frequencies of the mice in the Fmr1 KO group with unfamiliar mice (5.50[0.50, 12.75] times) was less than that in the WT group (7.00[4.00, 17.00] times) without significant difference ( P>0.05); that in the Fmr1 KO+BF839 group (23.00[16.00, 36.00] times) was significantly increased as compared with that in the Fmr1 KO group and WT group ( P<0.05). The contact duration of mice in the Fmr1 KO group with unfamiliar mice (9.50[0.50, 41.95] s) was significantly shorter than that in the WT group (142.00[65.00, 171.60] s, P<0.05); Fmr1 KO+BF839 group had significantly longer contact duration with unfamiliar mice (69.60 [50.40, 98.40] s) than Fmr1 KO group ( P<0.05); the contact duration of mice in Fmr1 KO+BF839 group with unfamiliar mice was shorter than that in WT group without significant difference ( P>0.05). Conclusion:Early BF839 intervention can significantly improve the learning, memory abilities and social novelty of Fmr1 KO mice, and even restore the Fmr1 KO mice to normal levels, which suggests that BF839 may become a new tool for treatment of fragile X syndrome and autism.

Objective: To compare the pharmacokinetics and bioavailability of pirfenidone in the fasted and fed states in healthy volunteers. Methods: An open-label, randomized crossover study was conducted in 12 healthy subjects. Food effects were examined by comparing pharmacokinetic data of pirfenidone after administration of a single oral 400 mg dose under fasted or fed conditions. Plas-ma pirfenidone concentration was determined by an HPLC method and its pharmacokinetic parameters were calculated with DAS v2. 0 software. Results: Under fasted and fed conditions, the concentration-time profiles of pirfenidone were fitted a one-compartment model and the pharmacokinetic parameters were as follows: t1/2were (2. 16 ± 0. 47) and (2. 05 ± 0. 42) h;tmaxwere(0. 69 ± 0. 16)and (1. 46 ± 0. 40)h;Cmaxwere (12. 95 ± 1. 79) and (9. 16 ± 2. 87) mg·L-1;AUC0-12were (44. 97 ± 15. 06) and (36. 19 ± 14. 44) mg·h·L-1;AUC0-∞were (46. 55 ± 16. 79) and (37. 41 ± 15. 43) mg·h·L-1, respectively. When compared with that of the fasted group, tmaxwas significantly increased (P<0. 001) while Cmaxand AUC were remarkedly decreased in the fed group (P<0. 001 and P<0. 01, respectively). Conclusion: Concomitant food intake significantly influences the pharmacokinetics and bioavail-ability of pirfenidone as indicated by reducing its extent and rate of absorption, which is associated with better tolerability.

Objective: To analyze the burden of disease attributable to low fruit intake among Chinese population aged ≥15 years old between 1990 and 2013. Methods: We used data from the 2013 Global Burden of Disease Burden of Disease Study to study the situation in China. The population attributable fraction was calculated to estimate and compare the death and disability-adjusted life years (DALY) attributed to low fruit intake between 1990 and 2013 in China (excluded Taiwan, China). An average world population age structure of the period 2000-2025 was adopted to calculate age-standardized rates. Results: Deaths attributable to low fruit intake accounted for 11.02% of all death in 2013, which were higher than it in 1990 (10.38%). In 2013, the number of deaths attributed to low fruit intake in China increased to 1 046 500 from 793 800 in 1990. From 1990-2013, the age-standardized death rate attributable to low fruit intake decreased from 113.04/100 000 to 79.80/100 000. DALYs caused by low fruit intake increased from 18.346 5 million in 1990 to 21.296 7 million in 2013. Compared with 1990, the age-standardized DALY rate attributed to low fruit intake decreased by 34.67%. In 2013, the top three provinces with the highest burden of disease attributed to low fruits intake were Tibet, Guizhou and Xinjiang provinces, with standardized DALY rate at 2 612.53/100 000, 2 281.85/100 000 and 2 198.22/100 000, respectively. Compared with the results in 1990, the standardized DALY attributed to low fruits intake decreased, especially in Tianjin, where decreased by 63.61%; followed by Aomen, Zhejiang, Shanghai and Beijing, where decreased by 59.74%, 59.53%, 56.64% and 53.88%, respectively. Conclusion Compared with the situation in 1990, the burden of disease attributable to low fruit intake decreased in 2013, but the situation is still serious, especially in Tibet, Guizhou and Xinjiang provinces, where the burden decreased comparatively slowly.

Objective To retrospectively analyze adverse drug reaction ( ADR ) of Yuxingcao ( Houttuyniae Herba ) preparations, thus provide reference for post-market re-evaluation of traditional Chinese medicine injections. Methods The ADR from Chinese ADR spontaneous reporting system database from 2006 to 2008 were analyzed by descriptive statistic method. Results A total of 2 282 reports on ADR induced by Yuxingcao preparations were concluded in this study, and 98.07% ADR of the total cases ( 2 238 case ) were due to vein injection. The main ADR were anaphylactic reactions which injure multiple systems and organs.The most frequent symptoms were respiratory system damage, such as expiratory dyspnea (with the incidence rate of 27.25%).Skin and mucous membrane were the secondly susceptible (with the incidence rate of 21.35%).The ratio of serious ADR in the total case was 13.50% (308 case), rate of allergic shock was 8.37% (191 case), and 22 cases were dead. Conclusion By strengthening the ADR reporting and monitoring, the risk of traditional Chinese medicine injection could be controlled.Safety re-evaluation should be performed to overall enhance safety, effectiveness and quality control of these kinds of medicine.

Objective To study the effects of pirfenidone on total enzyme and isoenzyme of liver microsomal cytochrome P450 in rats. Methods The activites of liver microsomal dimethyl nitrosamine N-demethylase( NDMA )and erythromycin demethylase( ERD ) were determined. Fifty-six SD rats were randomly divided into six groups,in which they received CMC,dexamethasone 100 mg·kg-1 ,ketoconazole 40 mg·kg-1 ,pirfenidone 25,50,100 mg·kg-1 ,respectively. After administration for 6 and 12 days,livers were prepared liver microsome,the concentration of proteinum in microsome and shade selection to plasma samples were determined by spectrophotometer. Results After administration of pirfenidone for 6 days, cytochrome P450 was significantly increased in 50 and 100 mg·kg-1 pirfenidone groups,as compared with solvent control group (1%sodium carboxymethylcellulose)(P﹤0. 01). After administration of pirfenidone for 6 and 12 days,NDMA of liver microsome was not changed significantly(P﹥0. 05). ERD of liver microsome was significantly increased in 100 mg·kg-1 pirfenidone group after administration for 12 days(P﹤0. 01). Conclusion Pirfenidone can induce P450 and ERD activities in a dose-and time-dependent manner.

ObjectiveTo explore the effect of TLR4,PI3K and NF-κB on the migration of asthmatic airway smooth muscle cell(ASMCs) induced by airway epithelial cells.MethodsPrimary ASMCs were cultured by the method of cell digestion.Cell culture supernatant of RTE cells were collected by TNF-α stimulation of epithelial cells.Detected the IL-8 and RANTES levels in the supernatant.The effect of TLR4/PI3K-related signaling molecules on the migration of asthmatic ASMCs induced by epithelial cells were detected by Modified Boyden chemotaxis chamber with anti-TLR4 antibody,Wortmannin and PDTC drugs as a tool.ResultsThe levels of IL-8 and RANTES in the supernatant of TNF-αgroups were significantly increased,and that in the 20 ng/ml group was significantly higher than other groups ( P＜0.01 ).Compared with control group,the transmembrane migration of asthmatic ASMCs from other groups was significantly increased (P＜0.01 ).The transmembrane migration of asthmatic ASMCs from treated groups was significantly increased than asthma group (P＜0.01).The migration of asthmatic ASMCs from TNF-α+anti-TLR4 antibody group,TNF-α+Wortmannin group and TNF-α+Wortmannin+PDTC were significantly decreased than that of TNF-αgroup( P＜0.01 ).The migration of asthmatic ASMCs from TNF-α+Wortmannin+PDTC were significantly decreased than that of TNF-α+Wortmannin group (P＜0.05).ConclusionTLR4/PI3K-related signaling molecules involved in the transmembrane migration of asthmatic ASMCs induced by airway epithelial cells and may be one of the mechanisms of airway remodeling of asthma.

The research team on the National Key Scientific Program of China: "Transcriptomic regulation and molecular mechanism research of polygenic tumor at different stages" has focused on the field of transcriptomics of 4 common polygenic tumors, including nasopharyngeal carcinoma(NPC), breast cancer, colorectal cancer, and glioma. Extensive laboratory work has been carried out on the expression and regulation of tumor transcriptomics; identification of tumor suppressor/susceptible genes; mechanism of tumor epigenetics including miRNAs, and comparative study of specific gene/protein cluster of tumor transcriptomics and proteomics. Genes including SPLUNC1, LTF, BRD7, NOR1, BRCA1/2, PALB2, AF1Q, SOX17, NGX6, SOX7, and LRRC4 have been identified as the key transcriptional regulation genes during the stage of tumor initiation and invasion. Accordingly,the NPC gene signal regulation network of "SPLUNC1-miR-141-target genes", the breast cancer interaction signal pathway of "miR-193b-uPA",the glioma signal network of "miR-381- LRRC4-MEK/ERK/AKT", and the miRNA-target gene network of colorectal cancer metastasis related gene NGX6 have been thoroughly elucidated. These fruitful Results imply that the changes of key molecules in crucial signal pathway will cause severe dysfunction in signal transduction and gene regulation network in polygenic tumors, indicating that in the category of pathogenesis,these tumors may further classify as the "Disease of gene signal transduction and gene regulation network disorder". The researches have laid solid foundation for revealing the molecular mechanism and transcriptomic regulation of polygenic tumors at different stages.
Animals ; Brain Neoplasms ; genetics ; pathology ; Breast Neoplasms ; genetics ; pathology ; Colorectal Neoplasms ; genetics ; pathology ; Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks ; Glioma ; genetics ; pathology ; Humans ; MicroRNAs ; genetics ; Multifactorial Inheritance ; Nasopharyngeal Neoplasms ; genetics ; pathology ; Neoplasm Proteins ; genetics ; Neoplasm Staging ; Neoplasms ; genetics ; Transcription, Genetic ; Transcriptome ; Tumor Suppressor Proteins ; genetics