OBJECTIVETo investigate the levels of IL-18 in the bone marrow of both normal subjects and patients with hematological diseases and to determine the possible significance of IL-18 in pathogenesis of some hematological malignancies.

METHODSThe IL-18 mRNA levels in the bone marrow of 140 patients with hematological diseases and 15 normal donors were determined by the semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR). Immunohistochemical method was used to detect IL-18 protein in 12 patients with acute myeloid leukemia (AML). The possible regulation of IL-18 for proliferation of some leukemia cells was investigated using antisense techniques.

RESULTSIL-18 mRNA levels were obviously higher in the patients with leukemia or other malignant hematological diseases (OMHD) than in normal donors. However, no significant difference was found in the level of transcription between patients with iron deficiency anemia (IDA) and normal controls. Immunohistochemical method confirmed the presence of IL-18 protein in 10 out of 12 AML cases with positive transcription. By 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, IL-18 antisense oligodeoxynucleotides (ASON) clearly inhibited the growth of J6-1 and HL-60 cells (42% and 12% inhibited, respectively) in a dose-dependent manner.

CONCLUSIONSIL-18 was detected at elevated levels in the bone marrow of patients with some hematological malignancies, and might be involved in the proliferation of certain leukemic cells in vivo through an autocrine mechanism.

Adolescent ; Adult ; Bone Marrow ; metabolism ; Cell Division ; drug effects ; Dose-Response Relationship, Drug ; Female ; Humans ; Immunohistochemistry ; Interleukin-18 ; analysis ; antagonists & inhibitors ; genetics ; Leukemia ; drug therapy ; metabolism ; pathology ; Male ; Middle Aged ; Oligonucleotides, Antisense ; pharmacology ; RNA, Messenger ; analysis

Continuing medical education for general practitioners is an important measure to upgrade the quality of primary health care services in China, which is still facing various challenges and need to be further developed and improved. This article analyzes the status quo and existing problems of continuing medical education for general practitioners in China, and proposes suggestions based on the concept of people centered and integrated health care (PCIC), including faculty development, training contents, assessment methods, and experience learning, to provide references for the improvement of continuing medical education for general practitioners.

OBJECTIVE To evaluate the quality of different germplasms of Rehmannia glutinosa based on iridoid glycosides. METHODS The contents of total iridoid glycosides ，catalpol，rehmaionoside D ，rehmaionoside A ，and leonuride in 18 batches of R. glutinosa from 6 germplasms（85-5，JinJiu，BX，BJ-1，Shandong，QH-1）were determined by ultraviolet spectrophotometry and high performance liquid chromatography. After normalization of the above content determination results ，the quality of different germplasm of R. glutinosa were evaluated by multiple statistical methods such as cluster analysis ，factor comprehensive analysis and partial least squares discriminant analysis （PLS-DA）. RESULTS Among 6 germplasms of R. glutinosa ，the content of total iridoid glycosides in R. glutinosa 85-5 was the highest ，and the content of catalpol in R. glutinosa BX was the highest ；the contents of rehmannioside D and rehmannioside A in R. glutinosa JinJiu were the highest ，and the content of leonuride in R. glutinosa BX was the highest. Cluster analysis showed that R. glutinosa JinJiu were clustered into one category ，R. glutinosa BX clustered into one category ，R. glutinosa Shandong and R. glutinosa BJ-1 were clustered into one category ，and R. glutinosa QH-1 and 85-5 were clustered into one category. Through factor comprehensive analysis ，there were differences in the quality of different germplasms of R. glutinosa . The comprehensive score of R. glutinosa BX，Shandong，85-5，BJ-1，QH-1，JinJiu were 2.283 9，1.689 1，1.664 8， 1.503 3，1.469 0，1.214 6，respectively. PLS-DA showed that variable importance projection value of total iridoid glycosides ， catalpol and leonuride were all higher than 1. CONCLUSIONS The quality difference of R. glutinosa from different germplasms may be caused by total iridoid glycosides ，catalpol and leonuride.

OBJECTIVE： To establish a method for rapid determination of total phenylethanoid glycosides and total iridoid glycosides in the root of Rehmannia glutinosa. METHODS： The contents of total phenylethanoid glycosides and total iridoid glycosides in medicinal material samples were determined by UV spectrophotometry. Quantitative model of total phenylethanoid glycosides and total iridoid glycosides in medicinal samples was established by NIRS-PLS method. The optimal pretreatment spectra were multivariate scattering correction combined with first derivative method， standard normalization combined with first derivative method. The optimum spectral ranged from 6 703.35-11 065.54 cm－1 and 3 999.63-9 102.36 cm－1. The optimum principal factor number were 10 and 7. RESULTS： The content determination of total phenylethanoid glycosides and total iridoid glycosides in medicinal material samples was proved to meet the requirements by methodological experience. The internal cross validation determination coefficients of total phenylethanoid glycosides and total iridoid glycosides were 0.998 2 and 0.980 9. The correction of root mean square error was 0.032 7 and 0.186 0. The root mean square error of prediction were 0.035 5 and 0.035 1. The root mean square error of cross validation were 0.256 9 and 0.574 3. The predicted values of total phenylethanol glycosides and total iridoid glycosides were 0.268％-1.636％ and 3.424％-6.978％， respectively； the determination value of them were 0.299％-1.629％ and 3.431％-6.952％， respectively； the absolute deviations were －0.042％-0.067％ and －0.111％-0.088％， respectively；the relative deviations were －0.819％-0.076％、－2.257％-1.672％， respectively；There was no statistical significance between predicted values and measured values （P＞0.05）. CONCLUSIONS： The method is accurate and simple. The method can be used for the rapid determination of total phenylethanoid glycosides and total iridoid glycosides in different germplasms of R. glutinosa.

The mitogen-activated protein kinases (MAPK) pathway, often known as the RAS-RAF-MEK-ERK signal cascade, functions to transmit upstream signals to its downstream effectors to regulate physiological process such as cell proliferation, differentiation, survival and death. As the most frequently mutated signaling pathway in human cancer, targeting the MAPK pathway has long been considered a promising strategy for cancer therapy. Substantial efforts in the past decades have led to the clinical success of BRAF and MEK inhibitors. However, the clinical benefits of these inhibitors are compromised by the frequently occurring acquired resistance due to cancer heterogeneity and genomic instability. This review briefly introduces the key protein kinases involved in this pathway as well as their activation mechanisms. We also generalize the correlations between mutations of MAPK members and human cancers, followed by a summarization of progress made on the development of small molecule MAPK kinases inhibitors. In particular, this review highlights the potential advantages of ERK inhibitors in overcoming resistance to upstream targets and proposes that targeting ERK kinase may hold a promising prospect for cancer therapy.

Non-alcoholic fatty liver disease(NAFLD) has become the main cause of chronic liver disease in children worldwide, and the incidence of NAFLD shows an increasing trend year by year. The risk factors leading to the onset of NAFLD in children are diversified and different from those in adults. At present, most medical institutions still pay little attention to NAFLD in children. This paper summarizes the risk factors and mechanisms for NAFLD in children, including gene polymorphism, maternal and fetal conditions, diet and living habits, environmental exposure, metabolic syndrome, endocrine-related mechanisms and intestinal microecology, in order to provide reference for the prevention and management of childhood NAFLD.

Objective: To investigate the genetic characteristics of VP1 coding region of enterovirus Coxsackievirus A16(CV-A16) and etiological features of hand, foot and mouth disease (HFMD) in 2017 in Xining city. Methods: The pharyngeal swab specimens were collected from HFMD patients, and detected by real-time reverse transcription-polymerase chain reaction (RT-PCR). For CV-A16 positive samples, virus isolation was performed. Then RNA was extracted, and then VP1 coding region was amplified by RT-PCR. The phylogenetic tree was constructed by comparing with other genotypes and sub-genotypes strains of EV-A71. Results: It was shown that 70 strains of CV-A16 were isolated from 2017 to 2018 in Xining city. In 2017, 10 strains were isolated and divided into two different lineages by phylogenetic analysis, 3 strains of B1a and 7 stains of B1b. In 2018, 60 stains were isolated, which were all belong to B1b. Conclusions B1a and B1b of CV-A16 are prevalent in Xining city from 2017 to 2018, in which B1b is the prominent isolates.

ObjectiveTo analyze the changes of volatile organic compounds （VOCs） and bacterial community characteristics in rhizosphere soil during the growth of Rehmanniae Radix， as well as the relationship between VOCs and bacterial community structure， so as to lay the foundation for the evaluation of the characteristics of continuous cropping soil and the regulation of continuous cropping soil microorganisms. MethodThe rhizosphere soil during the three main growth periods of Rehmanniae Radix in July， August and October was used as the research object. Gas chromatography-mass spectrometry （GC-MS） was used to determine the relative contents of VOCs in ethyl acetate and dichloromethane parts in rhizosphere soil. The characteristics of rhizosphere bacterial community structure was determined by high-throughput sequencing， SPSS 24， SIMCA 14.1 and other software were used to analyze the differences of VOCs and bacterial community structure in rhizosphere soil of the three periods， and the main VOCs and iconic bacteria that caused the differences were screened， and the correlation between VOCs and bacterial community structure was analyzed. ResultThere were differences in VOCs in different parts of rhizosphere soil during the three growth stages of Rehmanniae Radix. Among them， and the main VOCs that cause differences were dioctyl isophthalate， 2-octyl-1-dodecanol and 2-ethylhexyl p-toluic acid in the ethyl acetate part， and 1，3-benzenedicarboxylic acid， di （2-propylpentyl） phthalate and 2-ethylhexyl p-toluenecarboxylic acid in the dichloromethane part. From the seedling stage to the end of tuber enlargement of Rehmanniae Radix， the relative abundance of dominant bacteria such as Actinobacteria， Firmicutes and Chloroflexi in the rhizosphere soil was gradually decreased， and there were unique bacterial communities in rhizosphere soil of each growth stage. Correlation analysis showed that the VOCs in rhizosphere soil of Rehmanniae Radix had an impact on the rhizosphere bacterial community structure， especially the components of esters and alcohols. ConclusionDuring the growth of Rehmanniae Radix， the characteristics of rhizosphere soil are mainly manifested in the content changes of main VOCs such as esters and alcohols and the gradual decrease of the abundance of the main beneficial bacteria， and the VOCs in rhizosphere soil play a certain role in shaping the structure of bacterial community.

ObjectiveTo analyze the effect of different fixation methods on the chemical quality characteristics and antioxidant activity of Rehmannia glutinosa leaves， so as to lay a foundation for the selection of processing technology and quality evaluation of this medicinal materials. MethodR. glutinosa leaves was dried at 55 ℃ after treating by three fixation methods （55 ℃， boiling water， 105 ℃）， and then the fingerprints of R. glutinosa leaves were collected by high performance liquid chromatography （HPLC） and near infrared spectroscopy （NIRS）， and their antioxidant activities were analyzed by the 2，2-biphenyl-1-picrylhydrazyl （DPPH） method. Finally， similarity analysis， principal component analysis （PCA）， orthogonal partial least squares-discriminant analysis （OPLS-DA） and Pearson correlation analysis were used to comprehensively evaluate the quality of R. glutinosa leaves with different fixation methods. ResultThe results of HPLC and NIRS fingerprint analysis indicated that there were differences in the quality characteristics of R. glutinosa leaves by different fixation treatments. The comprehensive score of chemical quality of R. glutinosa leaves by fixation at 55 ℃ was the highest， its average comprehensive score was 2.096， followed by fixation at 105 ℃， and the lowest was fixation with boiling water. The antioxidant activity of sample with fixation at 55 ℃ was the highest， followed by fixation with boiling water. The results of OPLS-DA showed that verbascoside， isoacteoside and catalpol were the main components causing the difference in chemical quality of the leaves from the three treatments， and the three components were positively correlated with the antioxidant activity of R. glutinosa leaves. Among them， the correlation between verbascoside and antioxidant activity was extremely significant， and the isoacteoside was significant. ConclusionThe chemical quality and antioxidant activity of R. glutinosa leaves are affected by the method of fixation， and the fixation at low temperature is the best primary processing method of R. glutinosa leaves.