OBJECTIVETo investigate the significance of H3K27me3 and its methyltransferase EZH2 in predicting the short-term and long-term outcome of newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL).

METHODSThe paraffin wax speciments of 102 DLBCL patients in Fujian Medical University Cancer Hospital were collected. The expression of H3K27me3, EZH2 and BCL-2 protein were detected using tissue array made by tissue microarray(TMA) technique and immunohistochemistry method. The evaluation data after clinical treatment and follow-up results were collected and combined with expression levels of H3K27me3, EZH2 and BCL-2 detected by tissue array, then on the basis of these data, the survival of patients was analyzed by Kaplan-Meier method, the correlation of EZH2 with H3K27me3 and BCL-2 was analyzed by pearson correlation test, the correlation of above mentioned indicators with different therapeutic efficacy was analyzed by spearman correlation test. The relationship of H3K27me3 and EZH2 expression as well as co-expression of H3K27me3 and EZH2 with the therapeutic efficacy and prognosis of patients were compared.

RESULTSA total of 61.8% patients showed EZH2 high expression which positively correlated with high expression of H3K27me3 and BCL-2. The complete remission (CR) and overall remission (OR) rates in H3K27me3 high expression and co-expression of H3K27me3 EZH2 groups were lower than those in low expression groups (P<0.001), moreover OS and PFS rates also were lower than those in low expression (P<0.001). In the RCHOP subgroup, the patients with EZH2 low expression showed significantly better CR, OR OS and PFS in comparison with those of patients with higher expression (P=0.003,P=0.019).

CONCLUSIONPart of DLBCL patients with H3K27me3 high expression or coexpression of both H3K27me3 and EZH2 exhibit a worse prognosis in comparison with those patients with H3K27me3 low expression or without coexpression. The patients with EZH2 low expression usually responde well to RCHOP regimen in the short-term or long-term survival.

OBJECTIVETo investigate the role of calcium/calmodulin-dependent protein kinase II (CaMKII) in myocardial ischemia-reperfusion (IR) injury in isolated perfused rat heart and explore the underlying mechanisms.

METHODSAn ischemia-reperfusion (IR) model was prepared using isolated rat hearts perfused with Krebs-Henseleit solution were randomly divided into control group, 2.5 µmol/L KN-93 group, IR (induced by ischemia for 45 min followed by reperfusion for 120 min) group and KN-93+IR group. The myocardial performance was evaluated by assessing the left ventricular pressure. Lactate dehydrogenase (LDH) activity and cTnI content in the coronary flow and the infarct size were determined to evaluate the myocardial injury. The phosphorylation of CaMKII (p-CaMKII) and PLN (p-PLN) and oxidation of CaMKII (ox--CaMKII) were measured with Western blotting. The activity of mitochondrial superoxide dismutase (SOD) and the content of malondialdehyde (MDA) were determined using ELISA.

RESULTSCompared with the control group, KN-93 treatment at 2.5 µmol/L produced no significant effects on cardiac function or performance in rat hearts without IR injury. Myocardial IR injury significantly decreased myocardial performance and mitochondrial SOD activity in the perfused hearts (P<0.01) and caused significantly increased infarct size, LDH activity, cTnI content, expressions of p-CaMKII, ox-CaMKII and p-PLN, and also increased mitochondrial MDA content (P<0.01). KN-93 treatment at 2.5 µmol/L administered before ischemia and before reperfusion markedly attenuated such changes induced by ischemia and reperfusion (P<0.01).

CONCLUSIONCaMKII participates in myocardial IR injury in isolated rat heart, and inhibiting CaMKII can alleviate myocardial injury by relieving mitochondrial oxidation stress.

BackgroundMicroRNAs (miRNAs) have been reported to play vital roles in liver regeneration. Previous studies mainly focused on the functions of intracellular miRNAs, while the functions of circulating exosomal miRNAs in liver regeneration remain largely unknown. The aim of this study was to identify the key exosomal miRNA that played vital roles in liver regeneration.

MethodsThe Sprague-Dawley male rats were assigned to 70% partially hepatectomized group (n = 6) and sham surgery group (n = 6). The peripheral blood of both groups was collected 24 h after surgery. The exosomal miRNAs were extracted, and microarray was used to find out the key miRNA implicated in liver regeneration. Adenovirus was used to overexpress the key miRNA in rats, and proliferating cell nuclear antigen (PCNA) staining was applied to study the effect of key miRNA overexpression on liver regeneration. Western blotting was used to validate the predicted target of the key miRNA.

ResultsExosomal miR-10a was upregulated more than nine times in hepatectomized rats. The level of miR-10a was increased in the early phase of liver regeneration, reached the top at 72 h postsurgery, and decreased to perioperative level 168 h after surgery. Moreover, enforced expression of miR-10a by adenovirus facilitated the process of liver regeneration as evidenced by immunohistochemical staining of PCNA. Erythropoietin-producing hepatocellular receptor A4 (EphA4) has been predicted to be a target of miR-10a. The protein level of EphA4 was decreased in the early phase of liver regeneration, reached the bottom at 72 h postsurgery, and rose to perioperative level 168 h after surgery, which was negatively correlated with miR-10a, confirming that EphA4 served as a downstream target of miR-10a. Moreover, inhibition of EphA4 by rhynchophylline could promote the proliferation of hepatocytes by regulating the cell cycle.

ConclusionExosomal miR-10a might accelerate liver regeneration through downregulation of EphA4.

The widespread application of next generation sequencing (NGS) in clinical settings has enabled testing, diagnosis, treatment and prevention of genetic diseases. However, many issues have arisen in the meanwhile. One of the most pressing issues is the lack of standards for reporting genetic test results across different service providers. The First Forum on Standards and Specifications for Clinical Genetic Testing was held to address the issue in Shenzhen, China, on October 28, 2017. Participants, including geneticists, clinicians, and representatives of genetic testing service providers, discussed problems of clinical genetic testing services across in China and shared opinions on principles, challenges, and standards for reporting clinical genetic test results. Here we summarize expert opinions presented at the seminar and report the consensus, which will serve as a basis for the development of standards and guidelines for reporting of clinical genetic testing results, in order to promote the standardization and regulation of genetic testing services in China.

Along with the increase of clinical application, the safety of traditional Chinese medicine gained more and more attentions. In particular, the safety evaluation of Chinese medical injections has become a mandatory task should be completed by pharmaceutical companies under the supervision of China Food and Drug Administration(CFDA). Due to the weak foundation of previous studies, the safety issues of Chinese medical injections have not been fully understood, and lack of scientific and rational risk management programs. Clinical safety centralized monitoring(CSCM) is an important method for post-market safety evaluation of Chinese medicine. Due to the lack of appropriate norms and procedures, the quality of similar research is uneven, and the results vary. Combined with practical experience with experts' suggestions, we developed this expert consensus on the design and implementation of CSCM from three stages (design, implementation and report) with 20 technical points, which will provide technical support for future CSCM studies.

OBJECTIVETo study the association between depression during pregnancy and low birth weight in neonates, and to provide a scientific basis for the prevention of low birth weight.

METHODSCohort studies on the association between depression during pregnancy and low birth weight were collected and a Meta analysis was performed. Data were extracted independently by two investigators, and quality assessment was performed according to Newcastle-Ottawa Scale. The Egger's test was used to evaluate publication bias.

RESULTSA total of 12 cohort studies with 37 192 samples were included. The results of the Meta analysis showed that depression during pregnancy was associated with low birth weight (Z=2.08, P=0.038), and the neonates whose mothers had depression during pregnancy tended to have a high risk of low birth weight (RR=1.303, 95%CI: 1.015-1.672). The sensitivity analysis showed that the results of this Meta analysis were stable and reliable, and the Egger's test showed no publication bias.

CONCLUSIONSDepression during pregnancy may be a risk factor for low birth weight in neonates.

OBJECTIVETo investigate the major risk factors for congenital heart disease (CHD) in Chinese neonates and to provide a reference for the prevention of CHD.

METHODSA literature search was performed to collect the case-control studies on the risk factors for CHD in Chinese neonates published in 2001-2016. The relevant data were extracted accordingly. The quality of included studies was assessed by Newcastle-Ottawa Scale. Sensitivity analysis was conducted using different models to analyze the same data. The publication bias was assessed by Egger's test.

RESULTSA total of 17 case-control studies involving 2 930 cases and 4 952 controls were included. The Meta analysis showed that the major risk factors for CHD in Chinese neonates were as follows: mother with advanced age (OR=2.649, 95%CI: 1.675-4.189), cold or fever (OR=4.558, 95%CI: 2.901-7.162), medication use in early pregnancy (OR=3.961, 95%CI: 2.816-5.573), passive smoking (OR=2.766, 95%CI: 1.982-3.859), abnormal childbearing history (OR=2.992, 95%CI: 1.529-5.856), noise exposure (OR=3.030, 95%CI: 1.476-6.217), radiation exposure (OR=2.363, 95%CI: 1.212-4.607), decoration (OR=4.979, 95%CI: 3.240-7.653), gestational diabetes (OR=5.090, 95%CI: 3.132-8.274), and pet raising (OR=2.048, 95%CI: 1.385-3.029).

CONCLUSIONSMothers with advanced age, cold or fever, medication use in early pregnancy, passive smoking, abnormal childbearing history, noise exposure, radiation exposure, decoration, gestational diabetes, and pet raising may increase the risk of CHD in Chinese neonates.

Obsjective:To investigate the effects of differentaction time of IL-1β on the osteogenic capacity of bone marrow mensenchymal cells(BMMSC) and the role of nuclear factor-κB (NF-kB) pathway.

METHODSBMMSC isolated from normal donors was treated with IL-1β for 1 or 7 days, respectively. Alkaline phosphatase (ALP) and alizarin red(AR) stainings were used to detect the osteogenic differentiation potential of BMMSC. The mRNA expression of EphB4, IGF-1 and OPG in BMMSC was measured by real-time PCR. The immunohistochemistry was employed to measure the expression of bone morphgenetic protein-2(BMP-2) and p-Smad1/5/8 in BMMSC. Furthermore, the Western blot was used for the detection of iκBα and phospho-iκBα (p-ikBα) in IL-1β-treated BMMSC. And the results of IL-1β-treated BMMSC were compared with control group.

RESULTSCompared with control group, the osteogenetic potential of IL-1β-treated BMMSC was enhanced, but the pro-osteogenic differentiation effect of IL-1β was remarkedly inhibited in the presence of NF-kB pathway inhibitor PDTC. The total ikBα level of IL-1β-treated BMMSC was lower (P<0.05), and phospho-iκBα (p-iκBα) level was higher (P<0.05). Besides, BMP-2 expression was higher (P<0.05) in the IL-1β-treated BMMSC, however, p-Smad1/5/8 protien level was not significantly different among IL-1β-treated for 1 d, 7 d and control groups (P<0.05). And the mRNA expression levels of IGF-1, EphB4 and OPG in BMMSC were up-regulated after IL-1β treatment (P<0.05). In addition, the osteoblastogenesis of BMMSC treated with IL-1β for 7 days was significantly different from those treated only for 1 day.

CONCLUSIONProlonging IL-1β treatment can enhance the osteogenetic differentiation of BMMSC more significantly. And this osteogenetic alteration of BMMSC occurs via its NF-κB pathway, but not via BMP-2/Smad pathway.

In order to obtain the expression of ginsenoside biosynthetic pathway related enzyme gene in ginseng hairy root under the control of elicitors, methyl jasmonate (MeJA) was added exogenously as elicitors. Ginseng hairy root clones induced by 4-year-old ginseng root was used as material, total saponin content in ginseng hairy root before and after MeJA treatment was determined by vanillin-sulfuric acid colorimetry, Meanwhile, relative expression of squalene synthase genes, squalene epoxidase genes, oxidized squalene cyclase genes, dammarenediol synthase genes, β-amyrin synthase genes, cycloartenol synthase genes before and after MeJA treatment were determined by Real-time PCR. The optimum conditions of MeJA which added to ginseng hairy root were obtained, the optimum additional concentration was 6×10⁻⁴ μmol•L⁻¹, the optimum additional time was 22 d, and the optimum action time was 5 d. The addition of MeJA could improve the enzymatic activity of peroxidase (PPD), catalase (CAT) and peroxidase (PPD) in ginseng hairy root. The expression of SQS，SQE，OSC，DS and β-AS genes of ginsenoside biosynthetic pathway increased significantly after MeJA treatment, while the change of CAS gene expression were not significant. The expression of key enzyme SQS，SQE，OSC，DS and β-AS genes in ginsenoside biosynthetic pathway was consistent with the changes of PPD，CAT，PPO enzymatic activity.

OBJECTIVETo evaluate the stability of teaching robot of rotation-traction manipulation.

METHODSOperators were required to get the hang of rotation-traction manipulation and had clinical experience for over 5 years. The examination and data processing of the ten operators in our research were collected by the teaching robot of rotation-traction manipulation. Traction, pulling force, maximum force, pulling time, rotational amplitude and pitch range were recorded and compared for five times(G1, G2, G3, G4 and G5). The qualification rates were analyzed to evaluate the stability of teaching robot of rotation-traction manipulation.

RESULTSNonconforming items were found in G1 and G2, for instance, pulling force(=0.074), maximum force(=0.264) and rotational amplitude (=0.531). There was no statistically difference. None nonconforming item was found in G3, G4 and G5. All data were processed by SPSS and One-way ANOVA was used to analysis. Pulling force was found statistically different in G1, compared with G4 and G5(=0.015,=0.006). Maximum force was found statistically different in G1, compared with G4 and G5 (=0.021,=0.012). None differences were found in other comparisons (>0.05).

CONCLUSIONSThe teaching robot of rotation-traction manipulation used in our research could provide objective and quantitative indices and was considered to be an effective tool of assessing the rotation-traction manipulation.