Role of Histone Methyltransferase in Fibrosis and Traditional Chinese Medicine Treatment： A Review / 中国实验方剂学杂志

Fibrosis， a tumor-like lesion between benign tissue and malignant tumor， mostly occurs in the liver， kidney， heart， lung， bone marrow and other organs and tissues. It can affect almost every organ and eventually induce multiple organ failure and cancers， seriously endangering human life. It will be of great importance to prevent cancer if the disease can be opportunely blocked in the fibrotic stage. The pathogenesis of fibrosis is still not completely clear. It is of great clinical significance to study the occurrence， development， and mechanism of fibrosis as well as to screen new therapeutic targets. Enhancer of zeste homolog 2 （EZH2） is mainly located in the nucleus and involved in the formation of the polycomb repressive complex 2. EZH2 is a methyltransferase which makes the lysine on position 27 of histone H3 （H3K27me3） undergo trimethyl modification induces gene silencing through classical or nonclassical actions， so as to inhibit or activate transcription. EZH2 plays a critical role in cell growth， proliferation， differentiation， and apoptosis， which is regulated by different targets and signaling pathways. EZH2 regulates the transformation of myofibroblasts and participates in the fibrosis of multiple organs. Recent studies have shown that EZH2 plays a role in fibrosis-related pathophysiological processes such as epithelial-mesenchymal transition， oxidative stress， and inflammation. EZH2 as the target of fibrosis， EZH2 inhibitors， and EZH2-related traditional Chinese medicine （TCM） formula and active compounds have gradually become hot research directions. EZH2 may be a powerful target for organ fibrosis. Exploring the structure， function， and distribution of EZH2， the role of EZH2 in fibrosis， the EZH2 inhibitors， and TCM formulas and active components targeting EZH2 has great meanings. This paper reviews the research progress in EZH2 and fibrosis， providing new ideas for the diagnosis， treatment， and drug development of fibrosis.

EGFR-TKI Combined with Pemetrexed versus EGFR-TKI Monotherapy in Advanced EGFR-mutated NSCLC: A Prospective, Randomized, Exploratory Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#We aimed to evaluate whether the addition of pemetrexed is effective in improving progression-free survival (PFS) in epidermal growth factor receptor (EGFR)–mutated patients with or without concomitant alterations. @*Materials and Methods@#This multicenter clinical trial was conducted in China from June 15, 2018, to May 31, 2019. A total of 92 non–small cell lung cancer (NSCLC) patients harboring EGFR-sensitive mutations were included and divided into concomitant and non-concomitant groups. Patients in each group were randomly treated with EGFR–tyrosine kinase inhibitor (TKI) monotherapy or EGFR-TKI combined with pemetrexed in a ratio of 1:1. PFS was recorded as the primary endpoint. @*Results@#The overall median PFS of this cohort was 10.1 months. There were no significant differences in PFS between patients with and without concomitant and between patients received TKI monotherapy and TKI combined with pemetrexed (p=0.210 and p=0.085, respectively). Stratification analysis indicated that patients received TKI monotherapy had a significantly longer PFS in non-concomitant group than that in concomitant group (p=0.002). In concomitant group, patients received TKI combined with pemetrexed had a significantly longer PFS than patients received TKI monotherapy (p=0.013). Molecular dynamic analysis showed rapidly emerging EGFR T790M in patients received TKI monotherapy. EGFR mutation abundance decreased in patients received TKI combined chemotherapy, which supports better efficacy for a TKI combined chemotherapy as compared to TKI monotherapy. A good correlation between therapeutic efficacy and a change in circulating tumor DNA (ctDNA) status was found in 66% of patients, supporting the guiding role of ctDNA minimal residual disease (MRD) in NSCLC treatment. @*Conclusion@#EGFR-TKI monotherapy is applicable to EGFR-sensitive patients without concomitant alterations, while a TKI combined chemotherapy is applicable to EGFR-sensitive patients with concomitant alterations. CtDNA MRD may be a potential biomarker for predicting therapeutic efficacy.

Prediction and analysis of epitopes of hemagglutinin of measles virus / 中华流行病学杂志

Objective To discuss the antigenic change caused by the mutation of amino acid on the epitopes of the hemagglutinin of measles virus.Methods The B cell linear epitopes in the hemagglutinin were predicted with bioinformatics software.Peptide pairs,which located on the same region but originated from measles vaccine and wild-type virus respectively,were designed and synthesized.After detecting the immunogenicity of peptides with indirect ELISA assay,sera against each peptide was prepared.Antigenic specificity between the two peptides within each peptide pair were tested by using cross ELISA assay,and then antigen ratios were calculated.Results All the synthesized peptides could bind with immune sera against measles virus,of which the peptide pair CW23/CW22 designed on the epitope region (273-282 aa) possessed the highest binding ability,while the peptide pair CW150/CW151 designed on the non-epitope region (418-427 aa) showed the lowest binding ability.The difference in antigenic specificity between the two peptides from different sources was significant.The antigenic ratio was up to 16 between CW23 (vaccine-originated) and CW22 (wild-type originated),and 2.877 ± 0.583 between CW123 (vaccine-originated) and CW124 (wild-type originated) (236-246 aa).On the non-epitope regions,the antigenic ratios was only 1.631 ± 0.481 between peptide pair CW125 and CW126(356-364 aa),but reached to 10.367± 1.617 between CW150 and CW151.Conclusion Although there were several conservative epitopes,specific amino acid mutation on the predicted epitope or non-epitope regions might cause the antigenic change of wild-type measles virus.

Application of Systems Biology in TCM Syndrome Classification of Chronic Hepatitis B and Posthepatitic Cirrhosis / 世界科学技术-中医药现代化

The characteristics and advantages of traditional Chinese medicine ( TCM ) diagnosis and treatment of chronic liver diseases are conducted on the individualized treatment based on TCM syndrome classification . In this study , the analysis of systems biology was carried out for TCM syndrome classification in chronic hepatitis B and posthepatitic cirrhosis . The relationship between TCM syndrome classification and genetic polymorphism , the difference of genes and protein expression profiles , the difference of urine metabolite , and the molecular mechanism of Different TCM Syndrome for Same Disease and Same TCM Syndrome for Different Diseaseswere discussed . The results showed that there are molecular biological basis in TCM syndrome classification in hepatitis B and posthepatitic cirrhosis . The systems biology based syndrome identification methods may be bene-ficial to form a new classification , and provide reference for the diagnosis and individual therapy of hepatitis B and posthepatitic cirrhosis .

Sensitive and rapid detection of Vibrio cholerae O139 by loop-mediated isothermal amplification / 中华微生物学和免疫学杂志

Objective To develop a loop-mediated isothermal amplification method for rapid diag-nosing Vibrio cholerae O139 in inspection department and small-scale laboratory. Methods Four primers (2 inner primer and 2 outer primer) for the LAMP test were designed by targeting the wbfR gene of Vibrio chol-erae O139, and the reaction condition and reaction system of LAMP were optimized. Thirty Vibrio cholerae O139, 13 Vibrio cholerae reference strains, 10 O1 biotype Vibrio cholera* and 32 other enterobacterias were analyzed and the LAMP results were determined by visual inspection or electrophoretie analysis . Results All of the Vibrio cholerae O139's amplification products were observed as green by visual inspection and had a ladder-like pattern on the gel, but O1 biotype Vibrio cholera* and other enterobacteria's products were dis-played as orange by visual examination and had no ladder-like pattern on the gel. In addition, the reaction time of the LAMP method was only 1.5 h and the detection limit of this assay was 63 CFU/reaction. Con-clnsion LAMP assay targeting the wbfR gene of Vibrio cholera* O139 is rapid, specific, and sensitive for the detection of Vibrio cholerae O139. This method not only reduced the dependence of complicated equip-ment but also had a potential for wider use in inspection department, small-scale laboratory, emergency mo-tor vehicles and field survey.

Severe acute respiratory syndrome-associated coronavirus genotype and its characterization / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To study the severe acute respiratory syndrome (SARS)-associated coronavirus genotype and its characteristics.</p><p><b>METHODS</b>A SARS-associated coronavirus isolate named ZJ01 was obtained from throat swab samples taken from a patient in Hangzhou, Zhejing province. The complete genome sequence of ZJ01 consisted of 29,715 bp (GenBank accession: AY297028, version: gi: 30910859). Seventeen SARS-associated coronavirus genome sequences in GenBank were compared to analyze the common sequence variations and the probability of co-occurrence of multiple polymorphisms or mutations. Phylogenetic analysis of those sequences was done.</p><p><b>RESULTS</b>By bioinformatics processing and analysis, the 5 loci nucleotides at ZJ01 genome were found being T, T, G, T and T, respectively. Compared with other SARS-associated coronavirus genomes in the GenBank database, an A/G mutation was detected besides the other 4 mutation loci (C:G:C:C/T:T:T:T) involved in this genetic signature. Therefore a new definition was put forward according to the 5 mutation loci. SARS-associated coronavirus strains would be grouped into two genotypes (C:G:A:C:C/T:T:G:T:T), and abbreviated as SARS coronavirus C genotype and T genotype. On the basis of this new definition, the ZJ01 isolate belongs to SARS-associated coronavirus T genotype, first discovered and reported in mainland China. Phylogenetic analysis of the spike protein gene fragments of these SARS-associated coronavirus strains showed that the GZ01 isolate was phylogenetically distinct from other isolates, and compared with groups F1 and F2 of the T genotype, the isolates of BJ01 and CUHK-W1 were more closely related to the GZ01 isolate. It was interesting to find that two (A/G and C/T) of the five mutation loci occurred in the spike protein gene, which caused changes of Asp to Gly and Thr to Ile in the protein, respectively.</p><p><b>CONCLUSION</b>Attention should be paid to whether these genotype and mutation patterns are related to the virus's biological activities,epidemic characteristics and host clinical symptoms.</p>

Detection of Measles Virus Hemagglutinin Gene by RT-PCR / 中国疫苗和免疫

Using RT-PCR, we can detect measles virus hemagglutinin gene (H gene) of 635bp length directly from measles vaccine strain Shanghai-191, Edmonston strain, nasopharyngeal aspirates and throat swabs of the measles patients. The primers of RT-PCR based on H gene sequence of measles virus did not give the same products from rubella virus and influenza viruses (A1, A3, B). By second PCR amplification, the minimum quantity of measles virus required to give a positive signal was<0.01TCID50. Since the IgM antibody positive rate in early stage of measles patients is always low, the specificity and sensitivity of RT-PCR method may help diagnosing measles cases.