2019年 · 第05卷第01期

循证医学（EBM）在过去的20年里在中国得到了推广，并在医学领域产生了巨大的影响。医学生、从业者和政策制定者已经利用来自精心设计和实施的研究的证据来优化决策。本文综述了近年来我国循证医学的进展。

Hodgkin’s lymphoma is a highly treatable malignancy. It has high cure rates yet there are many patients who relapse or are refractory to treatment. Traditionally, treatment has been with conventional chemotherapy; however, the development of brentuximab vedotin and immune checkpoint inhibitors has revolutionized the care of Hodgkin’s lymphoma. This is a review of the current advances in the management of Hodgkin’s lymphoma and a review of ongoing clinical trials in the field.

Treatment intended to lower cardiovascular (CV) risk in patients with diabetes has always been a primary goal of diabetes treatment. Due to the subdued effects of reducing hemoglobin A1c (HbA1c) on macrovascular complications, controlling other CV risk factors such as hypertension and hyperlipidemia instead of hyperglycemia has been the mainstay treatment to improve CV outcome in patients with type 2 diabetes mellitus (T2DM) until recent years. This review is intended to summarize and compare the results from the available cardiovascular outcome trials (CVOTs) for the two classes of glucose lowering drug: sodium-glucose cotransporter 2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1 RA). The results including the EMPA-REG, CANVAS program and DECLARE-TIMI 58 trials for SGLT2i, and the ELIXA, LEADER, SUSTAIN-6, EXSCEL and HARMONY trials for GLP-1 RA were summarized. The potential mechanisms of these CV beneficial effects and the optimal CV risk reduction treatment in patients with T2DM based on patient risk stratification and evidence from these CVOTs in real-world setting were discussed.

Despite the widespread use of chronic dialysis for end-stage renal disease (ESRD), there is no consensus on the optimal timing of initiating renal replacement therapy. Over the past decade, a worldwide trend toward increasing glomerular filtration rate at the initiation of dialysis has been noted. However, available data indicate that early dialysis has no survival benefit or is harmful. Peritoneal dialysis (PD) is one alternative for ESRD and has potential survival factors different from those of hemodialysis. The association between the timing of PD initiation and survival is unclear. This review examines the effect of the timing of dialysis on clinical outcomes in PD patients.

Immuno-oncology is a fast evolving field of cancer therapy and immune checkpoint inhibitors (ICIs) are clearly a breakthrough in this field. Cardiotoxicity with conventional anti-cancer therapies has been well studied in the past and clear guidelines for management of these side effects are available in the literature. However, cardiotoxicity with novel agents such as ICIs has been fairly under-reported and/or underestimated and we are yet to formulate clear guidelines for management of these rare side effects. In the last few years, there has been an overall increase in the number of cases of cardiotoxicity related to ICIs. In this literature review, we describe the mechanism of action of the most widely used ICIs and their related cardiotoxicities. The increase in number of case reports about the potential of cardiotoxicities with these novel agents clearly indicates the need for a new insight into the field of cardio-immuno-oncology.

To explore genes potentially co-expressed with cyclin E in gastric cancer and discover possible targets for gastric cancer treatment.

The Cancer Genome Atlas (TCGA) stomach adenocarcinoma sequencing data were used to predict genes co-expressed with cyclin E. Co-expression genes predicted by cBioPortal online analysis with Pearson correlation coefficient ≥0.4 were analyzed by gene ontology (GO) enrichment annotation using the PANTHER online platform (Ver. 7). Interactions between proteins encoded by these genes were analyzed using the STRING online platform (Ver. 10.5) and Cytoscape software (Ver. 3.5.1). Genes displaying a high degree of connection were analyzed by transcription factor enrichment prediction using FunRich software (Ver. 3). The significant transcription factor and cyclin E expression levels and their impact on gastric cancer progression were analyzed by Western blotting and Kaplan-Meier survival curve analysis.

After filtering the co-expression gene prediction results, 78 predicted genes that included 73 protein coding genes and 5 non-coding genes with Pearson correlation coefficient ≥0.4 were selected. The expressions of the genes were considered to be correlated with cyclin E expression. Among the 78 genes co-expressed with cyclin E, 19 genes at the central of the regulatory network associated with cyclin E were discovered. Nuclear transcription factor Y subunit alpha (NF-YA) was identified as a significant transcription factor associated with cyclin E co-expressing genes. Analysis of specimen donors’ clinical records revealed that high expression of NF-YA tended to be associated with increased cyclin E expression. The expression of both was associated with progression of gastric cancer. Western blotting results showed that compared with normal tissues, NF-YA and cyclin E were highly expressed in tumor tissues (P < 0.001). Survival curve analysis clearly demonstrated relatively poor overall survival of gastric cancer patients with high cyclin E or high NF-YA expression level, compared to patients with low cyclin E or NF-YA expression (P < 0.05).

NF-YA may promote gastric cancer progression by increasing the transcription of cyclin E and other cell cycle regulatory genes. NF-YA might be a potential therapeutically useful prognostic factor for gastric cancer.

The aim of this study was to investigate the effect and possible mechanism of action of roof plate-specific spondin1 (Rspo1) in the apoptosis of rat bone marrow mesenchymal stem cells (BMSCs).

Osteogenic and adipogenic differentiation of BMSCs was identified by Alizarin Red and Oil Red O staining, respectively. BMSC surface markers (cluster of differentiation 29 [CD29], CD90, and CD45) were detected using flow cytometry. BMSCs were transfected with an adenoviral vector encoding Rspo1 (BMSCs-Rspo1 group). The expression levels of Rspo1 gene and Rspo1 protein in the BMSCs-Rspo1 group and the two control groups (untransfected BMSCs group and BMSCs-green fluorescent protein [GFP] group) were analyzed and compared by quantitative polymerase chain reaction and Western blot. The occurrence of apoptosis in the three groups was detected by flow cytometry and acridine orange-ethidium bromide (AO-EB) double dyeing. The activity of the Wnt/β-catenin signaling pathway was evaluated by measuring the expression levels of the key proteins of the pathway (β-catenin, c-Jun N-terminal kinase [JNK], and phospho-JNK).

Osteogenic and adipogenic differentiation was confirmed in cultured BMSCs by the positive expression of CD29 and CD90 and the negative expression of CD45. Significantly increased expression levels of Rspo1 protein in the BMSCs-Rspo1 group compared to those in the BMSCs (0.60 ± 0.05 vs. 0.13 ± 0.02; t=95.007, P=0.001) and BMSCs-GFP groups (0.60 ± 0.05 vs. 0.10 ± 0.02; t=104.842, P=0.001) were observed. The apoptotic rate was significantly lower in the BMSCs-Rspo1 group compared with those in the BMSCs group ([24.06 ± 2.37]% vs. [40.87 ± 2.82]%; t ＝49.872, P ＝0.002) and the BMSCs-GFP group ([24.06 ± 2.37]% vs. [42.34 ± 0.26]%; t ＝62.358, P ＝0.001). In addition, compared to the BMSCs group, the protein expression levels of β-catenin (2.67 ± 0.19 vs. 1.14 ± 0.14; t ＝－9.217, P ＝0.000) and JNK (1.87 ± 0.17 vs. 0.61 ± 0.07; t ＝－22.289, P ＝0.000) were increased in the BMSCs-Rspo1 group. Compared to the BMSCs-GFP group, the protein expression levels of β-catenin (2.67 ± 0.19 vs. 1.44 ± 0.14; t ＝－5.692, P ＝0.000) and JNK (1.87 ± 0.17 vs. 0.53 ± 0.06; t ＝－10.589, P ＝0.000) were also upregulated in the BMSCs-Rspo1 group. Moreover, the protein expression levels of phospho-JNK were increased in the BMSCs-Rspo1 group compared to those in the BMSCs group (1.89 ± 0.10 vs. 0.63 ± 0.09; t ＝－8.975, P ＝0.001) and the BMSCs-GFP group (1.89 ± 0.10 vs. 0.69 ± 0.08; t ＝－9.483, P ＝0.001).

The Wnt/β-catenin pathway could play a vital role in the Rspo1-mediated inhibition of apoptosis in BMSCs.

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