Objective To reveal the pathophysiological changes of sepsis, the plasma metabonomics of septic rats was determined and differential metabolites were determined by gas chromatography-mass spectrometry (GC-MS). Methods Male Spraguee-Dawley (SD) rats about 8 weeks were randomly divided into sham group (n = 18) and sepsis group (n = 24). Cecal ligation and puncture (CLP) was used to build sepsis model, while cecum was kept intact only in the sham group. 6 hours after the operation, rats were anesthetized, and blood was harvested through heart thoracotomy. Then the plasma metabonomics was detected by GC-MS and metabolic profile analysis was performed to find the relative differential metabolites.Results Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) showed that the metabolic profiling of the sepsis group was significantly different from the sham group. 259 kinds of metabolites were got by GC-MS, and 69 kinds of differential metabolites were found between sham group and sepsis group, in which 23 differential metabolites were related to amino acid metabolism. Compared with sham group, the contents of putrescine, N-glutamic acid, hydroxynorvaline, 3-cyanuric acid, D-alanyl-D-alanine and urea in the plasma of septic rats increased significantly, which ratios of sepsis/sham group were 10.876, 6.394, 2.800, 2.226, 1.323, 1.203, respectively (allP < 0.05). On the other hand, the contents of oxygen generation of proline, citrulline, glutamine, su-beta-hydroxy aspartic acid, citric acid, N-methyl-DL-alanine, serine, lysine, threonine, N-formyl-L-methionine, methionine, alanine, nicotinuric acid, N-methyl-L-glutamic acid, trans-4-hydroxy-L-proline, proline, L-glutamic acid in the plasma of septic rats decreased significantly, which ratios of sepsis/sham group were 0.858, 0.853, 0.834, 0.816, 0.816, 0.814, 0.813, 0.801, 0.793, 0.792, 0.774, 0.766, 0.748, 0.727, 0.716, 0.674, 0.603, respectively (allP < 0.05).Conclusions Through the GC-MS analysis of plasma metabonomics of septic rats, we found abnormal energy metabolism changes. The content of amino acid in plasma might be a method to evaluate the energy metabolism status of sepsis.

Objective: To investigate the changes of brain gray matter volume in patients with occupational noise-induced hearing loss by voxel based morphometry (VBM) . Methods: 16 age-and education-matched healthy controls and 42 patients with occupational noise induced hearing loss, including 27 in mild group and 15 in severe group, received MRI 3D-FSPGR sequence T1WI sagittal scan, and then underwent VBM of brain gray matter volume data analysis. Results: The brain gray matter volume of the left occipitotemporal lateral gyrus, the anterior cingulate gyrus, the bilateral angular gyrus, the precuneus and the near midline area of cerebellum differed between experimental group and control group (P<0.01) . Conclusion The volume of gray matter in specific brain areas of patients with occupational noise-induced hearing loss was changed, and the effect of noise on brain structure was revealed from the perspective of imaging.

Objective:To investigate the people's cardiopulmonary resuscitation (CPR) ability in Hunan Province and whether there are differences in the skill level of CPR among respondents of different ages and education levels.Methods:A self-made questionnaire was conducted to survey people in Hunan Province by means of WeChat from May 2018 to April 2019. The questionnaire referred to 2016 National consensus on cardiopulmonary resuscitation in China issued by Cardiopulmonary Resuscitation Specialized Committee of Chinese Research Hospital Association and 2017 version of American Heart Association (AHA) CPR operational guide, and combined with the CPR assessment scale of Hunan Provincial People's Hospital. The contents of the survey included the basic information of the subjects, the common knowledge and skills of first aid, the willingness to learn CPR skills and implement CPR, and the operational requirements of high quality CPR, etc. Results:A total of 6 563 people received the on-site first aid knowledge questionnaire, and 4 355 people completed and submitted the questionnaire. The recovery rate was 66.36%, of which 3 602 valid questionnaires were from IP in Hunan Province, and the qualified rate was 82.71%. Among the subjects, 1 532 were men (42.53%) and 2 070 were women (57.47%). The majority aged group from 19 to 30 (59.41%) and from 31 to 50 (36.70%). 307 were rural (8.52%) and 3 295 were urban (91.48%); and the majority levels of education were senior or technical secondary school (38.26%) and undergraduate or junior college (44.50%). Of the 3 602 respondents, 39.09% indicated that they had been exposed to CPR knowledge and only 0.36% indicated that they did not wish to participate in CPR training. 69.93% of the respondents said they would actively to help if they wet cardic arrest, and 97.92% of those were willing to do so if the patients were relatives or friends. The survey results showed that only 8.91% of respondents chose relatively high-quality CPR options (chest compressions were performed first, the pressing point was located in the sternum of the midpoint of bilateral nipple line, the pressing frequency was 100-120 times/min, pressing depth was 5-6 cm, the ratio of chest compression to artificial ventilation was 30∶2). Among these people, the correct rate was higher in the ages of 31-50 years old and ≤ 18, 19-30 than those ≥51 years old (12.71% vs. 0%, 6.87%, 8.70%, χ2 = 41.420, P < 0.01). The correct rate of education at graduate level and above was higher than those in junior middle school and below, high school or technical secondary school, undergraduate or junior college (19.57% vs. 2.07%, 3.41%, 13.72%, χ2 = 152.262, P < 0.01). Conclusions:The public in Hunan Province have a strong sense of first aid, and some of the theoretical knowledge of CPR. People between 31 years old and 50 years old of age and with graduate education and above know more about CPR, but the overall mastery of CPR skills is poor. It is necessary to further improve the ability of the public as the first witness by teaching various skills of CPR in various forms.

OBJECTIVETo investigate the effect of microRNA-140 (miR-140) on the migration and invasion of colorectal cancer (CRC) cells and the possible mechanism.

METHODSmiR-140 mimics, miR-140 specific inhibitor or small interfering RNA (siRNA) against Smad3 were transfected into human CRC cell line RKO cells respectively, using Oligofectamine or Lipofectamine2000. Quantitative real-time PCR (real-time PCR) was used to measure the expression levels of miR-140 and Smad3 mRNA. Smad3 protein was analyzed by Western blot. The in vitro cell migrating and invasive abilities were determined by wound-healing and Transwell chamber assay after up-regulating or down-regulating miR-140 or knocking down Smad3.

RESULTSThe Western blot assays showed that the Smad3 protein level was significantly reduced after up-regulating miR-140 (0.04 ± 0.01), compared with that of (0.47 ± 0.02, P < 0.05) in the control group and that of (0.52 ± 0.06) in the negative control group (P < 0.05 for both). The results of real-time PCR indicated that no significant difference was found in the levels of Smad3 mRNA between miR-140 transfection and NC groups (1.11 ± 0.13 vs. 1.00 ± 0.06, P > 0.05). The wound-healing assay showed that the migrating ability was dramatically attenuated by miR-140 compared with that in the control and NC groups, whereas no significance was found when compared with that of the Smad3 siRNA transfected cells. The number of cells migrating through Transwell chamber without matrigel in the miR-140 group was (76.2 ± 4.4), remarkably lowered than that in the control (267.1 ± 4.9) and NC (336.1 ± 5.7) groups (P < 0.05 for both), but no significant difference between the miR-140 (76.2 ± 4.4) and Smad3 siRNA (83.5 ± 7.3) groups. Transwell chamber with matrigel assay showed that number of cells penetrating through the membrane was (109.5 ± 7.4) in the miR-140 group, significantly lower than that in the control (403.1 ± 5.1) and NC (392.6 ± 8.4) groups (P < 0.05 for both), while Smad3 siRNA transfection had a similar effect (138.8 ± 3.6)(P > 0.05). Down-regulation of miR-140 increased the level of smad3 protein expression, and partially reversed the inhibition of the cell migration and invasion mediated by miR-140. Co-transfection of miR-140 inhibitor and Smad3 siRNA had no significant effect on the Smad3 protein expression and the abilities of cell migration and invasion.

CONCLUSIONSmiR-140 regulates the Smad3 expression at the post-transcriptional level. miR-140 suppresses the migrating and invasive abilities of CRC cells, possibly through down-regulation of Smad3. The findings of this study suggest that miR-140 may have a unique potential as a possible biomarker candidate for diagnosis and therapy of tumor metastasis.

Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Colorectal Neoplasms ; metabolism ; Down-Regulation ; Gene Expression Regulation, Neoplastic ; genetics ; Humans ; MicroRNAs ; Neoplasm Invasiveness ; RNA, Messenger ; RNA, Small Interfering ; Real-Time Polymerase Chain Reaction ; Smad3 Protein ; genetics ; metabolism ; Transfection ; Up-Regulation

[摘 要] 目的：用组织代谢组学方法，探讨甲状腺乳头状癌（papillary thyroid carcinoma, PTC）组织及癌旁组织的代谢差异，寻找PTC的潜在生物标志物，探索PTC的发病机制与治疗策略。方法：收集2018年10月至2020年2月期间湖南省人民医院乳甲外科手术切除的40例PTC患者的癌组织及癌旁组织标本。利用HPLC-MS技术平台对PTC组织及癌旁组织样本的差异性代谢物进行多维统计分析，寻找与PTC相关的异常代谢通路。结果：经PCA、PLS-DA、OPLS-DA分析得知癌组织和癌旁组织的代谢轮廓具有显著性差异。经OPLS-Loading plot分析，结合VIP>1、FC>2，且P<0.05，筛选出76个潜在差异性代谢物。其中亮氨酸、2-褪黑素、香草酸等33种代谢物在PTC组织中表达上调；3-葡萄糖苷、甘油磷脂、磷脂酰胆碱、乳糖等43代谢物在PTC癌组织中表达下调。寻找到与差异性代谢物相关的13条异常代谢通路，如半胱氨酸与蛋氨酸代谢、与甘油磷脂代谢、嘧啶代谢、半乳糖代谢以及丙氨酸、天冬氨酸和谷氨酸代谢、柠檬酸循环等，这些代谢通路可能参与PTC代谢的病理生理过程。ROC曲线下面积大于0.9的差异性代谢物有5种，分别是庚二酸、糖醇、辛二酸、乳糖和L-丝氨酸。结论：PTC组织中半乳糖代谢和氨基酸代谢发生改变，PTC组织细胞中存在沃伯格效应(Warburg effect)。庚二酸、糖醇、辛二酸、乳糖、L-丝氨酸五种差异性代谢物可以用来区分PTC患者与正常人。

Acute myocardial infarction with cardiogenic shock (AMI-CS) refers to the rapid decrease in cardiac output in a short period of time, and it leads to severe insufficient perfusion of various organs and causes systemic microcirculatory dysfunction, which is the most common cause of the death of patients with acute myocardial infarction (AMI). At present, the main strategy for clinical treatment of AMI-CS is revascularization, which reduces the mortality of AMI-CS. However, myocardial ischemia and reperfusion can cause ischemia/reperfusion (I/R) injury, induce myocardial mitochondrial dysfunction, and a large amount of reactive oxygen species (ROS) accumulation. Mitochondrial-mediated apoptosis of cardiomyocytes is the main reason of cardiomyocyte death during reperfusion injury. This article summarizes the role of mitochondrial in AMI-CS, which focus on three aspects of mitochondrial permeability transition pore (mPTP) opening, mitochondrial autophagy and mitochondrial fusion/division. It is expected to provide new ideas for clinical AMI-CS and identify potential complications targets.