[摘 要] 目的：探究SOX9通过上调长链非编码RNA LINC01503的表达对喉鳞状细胞癌（LSCC）细胞的增殖、迁移、侵袭及肿瘤干细胞干性的影响。方法： 常规培养人LSCC细胞AMC-HN-8、TU177、TU212和TU686，用转染试剂将敲减序列及其对照核酸（si-SOX9-NC、si-SOX9#1、 si-SOX9#2、si-LINC01503-NC、si-LINC01503#1、si-LINC01503#2）或过表达质粒及其对照核酸（pcDNA3.1-SOX-NC、pcDNA3.1-SOX-oe、pcDNA3.1-LIN01503-NC和pcDNA3.1-LIN01503-oe）分别转染至TU177细胞或TU686细胞，记为si-SOX9-NC组、si-SOX9#1组、si-SOX9#2组、si-LINC01503-NC组、si-LINC01503#1组、si-LINC01503#2组；pcDNA3.1-SOX9-NC组、pcDNA3.1-SOX9-oe组、pcDNA3.1-LINC01503-NC组、pcDNA3.1-LINC01503-oe组、si-SOX9-NC + pcDNA3.1-LINC01503-NC组和si-SOX9 + pcDNA3.1-LINC01503-oe组。qPCR法检测SOX9 mRNA和LINC01503 在各组细胞中的表达，生物信息学分析SOX9与LINC0503启动子区的结合位点，双萤光素酶报告基因实验和染色质免疫共沉淀实验验证SOX9与LINC01503启动子区是否直接结合，WB法检测SOX9的敲减效率及LINC01503对TU177和TU686细胞干性标志物表达的影响，MTS法检测各组细胞的增殖活力，划痕愈合和Transwell小室实验检测各组细胞的迁移能力，克隆形成实验检测各组细胞的克隆形成能力。结果：SOX9在各种LSCC细胞中呈高表达（均P < 0.05），数据库数据分析显示，在头颈部鳞状细胞癌中，SOX9与LINC01503表达呈正相关（R = 0.12，P = 0.005 9）；SOX9可与LINC01503启动子区直接结合并促进其转录表达（均P < 0.05）；敲减LINC01503可明显抑制TU177细胞的增殖、迁移、侵袭（均P < 0.05），过表达LINC01503明显促进TU686细胞增殖、迁移、侵袭的能力（均P < 0.05），提高TU686细胞克隆形成能力和细胞干性标志物分子CD133、OCT4、SOX2的mRNA和蛋白水平表达（均P < 0.05），敲减LINC01503则均可抑制TU686细胞的克隆形成和细胞干性标志物的表达（均P < 0.05）；敲减SOX9均可明显抑制TU177细胞的增殖、迁移和侵袭能力，降低其干性细胞标志物的表达（均P < 0.05），同时过表达LINC01503则可部分逆转敲减SOX9对TU177细胞恶性生物学行为和干性标志物表达的抑制作用（均P < 0.05）。结论：SOX9和LINC01503在LSCC细胞中呈高表达，SOX9可能通过上调LINC01503表达提高LSCC细胞增殖、转移和侵袭能力和肿瘤干细胞干性。

Objective:To analysis the clinical features of patients with acute myocardial infarction (AMI) presenting de Winter pattern on electrocardiogram.Methods:A total of 1 287 patients with AMI admitted to Beijing Luhe Hospital between June 2017 and January 2019 were enrolled in the study. Electrocardiogram and clinical features of 13 patients with AMI presenting de Winter pattern on electrocardiogram were analyzed and compared with anterior wall ST-segment elevation myocardial infarction(STEMI, n=206). Results:Among the 13 patients, 12 were males, aged (52.23±12.55) years old. Compared to patients with anterior wall STEMI, the age in the de Winter group was younger [(52.23±12.55)years vs. (59.79±12.46)years; t=-2.12, P=0.03], and the time from onset to appearing a typical ECG was shorter [109.0 (71.5, 152.0)min vs. 200.5 (120.0, 397.5)min; Z=-3.38, P<0.01]. Three cases showed a shifting between de Winter pattern and typical STEMI ECG: the de Winter ECG pattern progressed to STEMI in 2 cases, 1 case changed from STEMI to de Winter,then converted to STEMI again. The emergency angiography was performed in all 13 patients, angiography showed that proximal left anterior descending branch (LAD) was involved in 11 cases, mid LAD was involved in 1 case, and diffuse spasm occurred in all vessels in 1 case. The de Winter ECG pattern vanished in all patients after primary percutaneous coronary intervention or emergency angiography. Conclusions:The de Winter ECG pattern suggests an acute proximal or mid LAD artery occlusion, and the de Winter ECG pattern can be alternated with STEMI. The de Winter pattern should be recognized and revascularization should be given early.

In the past ten years, the research and application of microbiome has continued to increase. The microbiome has gradually become the research focus in the fields of life science, environmental science, and medicine. Meanwhile, many countries and organizations around the world are launching their own microbiome projects and conducting a multi-faceted layout, striving to gain a strategic position in this promising field. In addition, whether it is scientific research or industrial applications, there has been a climax of research and a wave of investment and financing, accordingly, products and services related to the microbiome are constantly emerging. However, due to the rapid development of microbiome sequencing and analysis related technologies and methods, the research and application from various countries have not yet unified on the standards of technology, programs, and data. Domestic industry participants also have insufficient understanding of the microbiome. New methods, technologies, and theories have not yet been fully accepted and used. In addition, some of the existing standards and guidelines are too general with poor practicality. This not only causes obstacles in the integration of scientific research data and waste of resources, but also gives related companies unfair competition opportunity. More importantly, China still lacks national standards related to the microbiome, and the national microbiome project is still in the process of preparation. In this context, the experts and practitioners of the microbiome worked together and developed the consensus of experts. It can not only guide domestic scientific research and industrial institutions to regulate the production, learning and research of the microbiome, the application can also provide reference technical basis for the relevant national functional departments, protect the scale and standardized corporate company's interests, strengthen industry self-discipline, avoid unregulated enterprises from disrupting the market, and ultimately promote the benign development of microbiome-related industries.
China ; Consensus ; Humans ; Industry ; Microbiota

Objective:To evaluate the feasibility of high concentrated contrast media combined with monochromatic images to improve image quality with double low scanning in dual-layer spectral coronary CT angiography.Methods:Fifty-six patients with suspected coronary artery disease were enrolled and randomly separated into two groups. All patients were scanned at 120 kVp in step-and-shoot mode using a dual-layer detector CT (IQon spectral CT). Patients were either injected with 18 ml high concentration contrast medium(400 mgl/ml) at 2 ml/s (group A) or 45 ml contrast medium (370 mgl/ml) at 4 ml/s (group B). Forty to 80 keV monoenergetic images with 10 keV increment and conventional image (group A2) were reconstructed for group A, conventional poly-energetic image was reconstructed for group B. Region of interest was placed on aorta root (AO), middle segment of left anterior descending (LAD), left circumflex (LCX) and right coronary artery (RCA) to measure the attenuation and noise, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). Image quality was assessed by two reviewers independently with a 4-point scale on image quality (1-undiagnostic,4-excellent). The objective and subjective image evaluation were compared using the Kruskal-Wallis test. The Steel Dwass was used for multiple comparisons between monoenergetic images in Group A and conventional images in Group B, after the Kruskal-Wallis test.Results:There were significant differences among the attenuation, noise, SNR and CNR of group B, group A2, and monoenergetic images(all P<0.001).The CT value in the aortic root was significantly higher at 40-50 keV monoenergetic images than that in group B(all P<0.05), and similarly, the CT value in LAD,LCX and RCA at 40 keV were superior than that in group B(all P<0.001). There was no significant difference in the noise of the aortic root among 40 keV image, group A2 and group B(all P>0.05),while the noise in the 50-80 keV monoenergetic images were significantly lower than that in Group B(all P<0.001). The SNR and CNR in the aortic root were significantly higher at 40-60 keV monoenergetic images than that in group B(all P<0.001).The SNR in LAD and RCA at 40，50 keV and the CNR in LAD and RCA at 40-60 keV were higher than that in group B(all P<0.01).The SNR at 40-60 keV and CNR at 40-70 keV in LCX were superior than that in group B(all P<0.05). There were significant differences among the subjective image quality score of group B, group A2, and monoenergetic images(all P<0.001).The subjective image quality score of 40，50 keV images were not significantly different from that in group B (all P>0.05),while the score in 60-80 keV image and group A2 were lower than that of Group B(all P<0.001). Conclusion:40，50 keV low monochromatic images derived from dual-layer spectral detect CT combined with high concentrated contrast media can provide comparable or superior image quality with double low scanning in CCTA study.

Objective: To explore the expressions of melanoma antigen (MAGE) -A9, -A11 and Ki67 in laryngeal squamous cell carcinoma (LSCC) tissues, and to analyze their correlation with clinicopathological features and the prognosisof LSCC patients. Methods: A total of 73 pairs of LSCC tissuesand corresponding para-cancerous tissues resected from LSCC patients, who were treated at the Fourth Hospital of Hebei Medical University from 2012 to 2014,were collected for this study. At the same time, testicular tissues from 3 patients with prostate cancer after castration were selected as positive control. The protein expressions of MAGE-A9, MAGE-A11 and Ki67 in LSCC tissues and its para-cancerous tissues were detected by immunohistochemistry. Results: The expression rates of MAGEA9, MAGE-A11 protein and Ki67 in LSCC tissues were 47.94% (35/73), 49.32% (36/73) and 46.58% (34/73) respectively, which were significantly higher than those in para-cancerous tissues. The protein expressions of MAGE-A9 and MAGE-A11 were correlated with clinical stage and lymphatic metastasis of LSCC (P<0.05). The expression of Ki67LI was correlated with tumor size, clinical stage and lymphatic metastasis of LSCC (P<0.05). The correlation analysis showed that the expressions of MAGE-A9 and MAGE-A11 were positively correlated with Ki67 (r=0.258, P＝0.027; r=0.672, P=0.001). Kaplan-Meier survival curve analysis showed that the survival rates of patients with high expression of MAGE-A9 protein (P=0.009), MAGE-A11 protein (P=0.031) and Ki67LI (P=0.040) were significantly lower than those with low expressions. And the survival time of patients with both high expressions of MAGE-A9 and Ki67LI (P=0.001) or both high expressions of MAGE-A11 and Ki67 (P=0.001) was significantly shorter than that of patients with low expression (both or single). Univariate and multivariate Cox regression analysis further indicated that MAGE-A9 protein (P=0.028) and MAGE-A11 protein (P=0.042) were independent prognostic factors for overall survival of LSCC patients. Conclusion: MAGE-A9, MAGE-A11 and Ki67 are tumor-associated antigens of LSCC, which can be used as prognostic indicators for LSCC.

To establish a time-resolved fluorescence immunochromatographic assay for quantitative determination of carbohydrate antigen 19-9 (CA19-9) in serum, we prepared CA19-9 test strips by integrating double-antibody sandwich method and fluorescence immunochromatography technique. Carboxy fluorescent microspheres and nitrocellulose membrane were used as carriers for labeling and coating CA19-9 pairing antibodies. We optimized the process by adjusting the amount of labeling and coating antibody. According to the linear range, lowest detection limit and precision, We evaluated the time-resolved fluorescence immunochromatographic assay of CA19-9. When the amount of labeled antibody was 80 μg for 20 μL fluorescent microspheres, and the concentration of coated antibody on the test line was 1.5 mg/mL, the optimal reaction time was 15 minutes. Assay linear range was 12.5 to 800 U/mL and the minimum detection limit was 6.32 U/mL. The Within-run and between-run coefficient of variation were less than 15%. Average recovery rate was 101%. By detecting 50 clinical samples in parallel with Roche electrochemical luminescence detection kit, correlation coefficient was 0.980 6. The experiment, initially established a fluorescence immunochromatographic detection method to quantitative detection of serum CA19-9, which has a good clinical application prospect.

Objective To compare the outcomes of patients with non-variceal upper gastrointestinal bleeding (NVUGIB) taking aspirin for primary prophylaxis to those not taking it.Methods Patients without any vascular disease (coronary artery or cerebrovascular disease) who were admitted to the 89th Hospital of PLA between 2006 and 2016 with non-variceal upper gastrointestinal bleeding were included.The frequencies of in-hospital mortality,re-bleeding,severe bleeding,need for surgery or embolization,and of a composite outcome of the 4 bleeding related adverse outcomes were compared between patients receiving aspirin and those on no antithrombotics.We also compared the frequency of in hospital complications and length of hospital stay between the two groups.Results Of the 179 eligible patients,47 were on aspirin and 132 patients were on no antithrombotics (control group).Patients in the aspirin group (58.4 years) were elder than that in controls (66.8 years) (P ＜0.01).Patients in the aspirin group had significantly more co-morbidities,including diabetes mellitus [25.5 ％ (12/47) vs 12.1％ (16/132)] and hypertension [46.8％ (22/47) vs 28.0％ (37/132)],respectively,as well as dyslipidemia [21.3％ (10/47) vs 6.1％ (8/132)] (P ＜ 0.01).Smoking was more frequent in the aspirin group [36.2％ (17/47) vs 22.7％ (30/132),P ＜ 0.05].The frequencies of endoscopic therapy and surgery were similar in both groups,while the frequencies of in-hospital complications and re-bleeding were similar in the two groups,too.However,the patients who were on aspirin had lower in hospital mortality rates (2.1％ vs 13.6％,P ＜0.01),shorter hospital stay (4.9 d vs 7.0 d,P ＜0.05),and fewer composite outcomes (10.6％ vs 24.2％,P ＜ 0.05).Conclusions Patients who present with NVUGIB while receiving aspirin for primary prophylaxis had fewer adverse outcomes.Thus aspirin may have a protective effect beyond its cardiovascular benefits.

Biological tests of medical devices is an important part to evaluate its biological safety. Good quality management of the test is a powerful guarantee to ensure the authenticity, integrity and reliability of the test results. This paper is based on the biological tests of medical devices, compares GLP and ISO/IEC 17025 which is widely used in China medical device testing institutions, describes the implementation of the GLP reference points to strengthen the quality management of biological tests of medical devices under the ISO/IEC 17025 system, to provide reference for quality management of medical device testing institutions.
China ; Equipment Safety ; Equipment and Supplies ; Reproducibility of Results

Objective:To provide basis for the rational use of valproic acid(VPA) in the patients with epilepsy through the analy-sis on the therapeutic monitoring data. Methods:The VPA plasma concentration and the other related information of 233 cases were analyzed retrospectively. Results:The total daily dose of VPA increased with age (P<0.05) in children group. Compared with that in adults group (19-50 years old),the target rate of VPA concentration was significantly higher in children group(4-14 years old) (P<0.001). VPA had similar antiepileptic effect in children and adults. Oral solution was the main dosage form for children and con-ventional tablets for adults. Children had higher target rate of VPA concentration than adults (P<0.05). Compared with the group with VPA alone,VPA combined with enzyme inducers such as carbamazepine,phenobarbital and phentoin significantly decreased the target rate of VPA concentration(P<0.001). Moreover,VPA combined with phenobarbital significantly decreased the total daily dose of VPA (P<0.05). Conclusion:With great inter-individual variance,VPA plasma concentration is associated with efficacy and side effects. Monitoring of VPA plasma concentration is useful to the individualized treatment of VPA.

Objective: To observe the effect of edaravone combining ulinastatin on brain protection in patients of type A aortic dissection (AAD) after total arch replacement. Methods: A total of 60 AAD patients with total arch replacement in our hospital from 2014-09 to 2016-01 were prospectively studied. Based on peri-operative application of edaravone and ulinastatin, the patients were divided into 2 groups: EU group: 1) the patients received ulinastatin 300000 U/8h and edaravone 0.5mg/Kg/12h from administration to 3 days post-operation, 2) during cardiopulmonary bypass, the patients received ulinastatin 300000 U/2h and edaravone 0.5mg/Kg; Control group, the patients had no such treatment.n=30 in each group. The following items were observed:①operative condition;②blood levels of speciifc brain injury markers as S-100 and neuron speciifc enolase (NSE) at different time points: beginning of surgery (T0), opening aorta clamp (T1), right after cardiopulmonary bypass (T2), entering ICU (T3), 24h post-operation (T4) and 3 days post-operation (T5); ③post-operative condition. Results:①Durations of operation, cardiopulmonary bypass, cardiac arrest and bilateral antegrade selective cerebral perfusion (BACP), the frequency of BACP and UACP (unilateral antegrade selective cerebral perfusion), the lowest rectal temperature and blood levels of S-100, NSE at T0 were similar between 2 groups.②Compared with Control group, EU group had decreased S-100 and NSE from T1 to T5,P<0.05.③The in-hospital and ventilation time, frequency of PND and TND, the patients with CSS score≥16 before discharge and the in-hospital death rate were similar between 2 groups,P>0.05. Conclusion: Edaravone combining ulinastatin had brain protective effect in AAD patients after total arch replacement;it may reduce blood speciifc brain injury markers while the clinical signiifcance should be further investigated.