脊髓神经元凋亡在鞘内注射血小板活化因子诱发大鼠痛敏中的作用

目的：探讨脊髓神经元凋亡在鞘内注射血小板活化因子（PAF）诱发大鼠痛敏中的作用。方法鞘内置管成功的雄性 Sprague-Dawley 大鼠60只,随机分为2组：对照组,30只,鞘内注射人工脑脊液（arti-ficial cerebral spinal fluid,ACSF）10μl;PAF 组,30只,鞘内注射 PAF 10μg,溶解于10μl 人工脑脊液;分别于鞘内给药前1 d、给药后1、3、5、7、14 d 分别测定机械痛阈（PWMT）和热痛阈（PWTL）。取 L4-6脊髓,采用TUNEL 法观察脊髓神经元凋亡。结果鞘内注射血小板活化因子（PAF）可诱发出大鼠机械性触诱发痛和热痛觉过敏。PAF 组术后1 d 脊髓中开始有少量凋亡神经元出现,凋亡指数于术后3 d 开始迅速增加,术后5 d 达峰值,与对照组比较,有显著性差异（P 〈0.01）。结论鞘内注射 PAF 诱发大鼠触觉异常痛敏和热痛敏,脊髓神经元凋亡可能参与了鞘内注射 PAF 大鼠痛敏的形成。     

Contrasting Trends of Primary Liver Cancer Mortality in Chinese Mongol and Non-Mongol

Background: This study aims to investigate the temporal trend as well as the burden of primary liver cancer among Mongol and non-Mongol in China. Materials and Methods: The registered data from up to 20 monitoring points in the periods of 2008 to 2015 in Inner Mongolia were used to calculate and model the trend of liver cancer among Mongol and non-Mongol using log-linear regression. Logistic regression was used to characterise the risk of liver cancer by using hospitalization records from 2008 to 2017. Results: Over the study period, significant reduction of liver cancer mortality was found among non-Mongol population (4.8/100,000 from 23.7/100,000 to 18.9/100,000, p=0.04), while the increase of liver cancer mortality was observed among the Mongolian population (8.4/100,000 from 10.7/100,000 to 19.1/100,000, p=0.02), particularly the Mongol from East (25.5/100,000 from 11.2/100,000 to 36.7/100,000, p=0.005). Comparing to the non-Mongol patients with primary liver cancer, the Mongolian patients were more likely to be from East Inner Mongolia (aOR=3.65, 95% CI:2.75-4.87) and those residing in urban area (aOR=2.11, 95%CI: 1.55-2.91). In 2015, a total of 3056 primary liver cancer deaths could be converted if the four known risk factors (HBV, Hepatitis C Virus, alcohol consumption and smoking) could be prevented. HBV remained to be the leading risk factor of liver cancer (PAF=56%, contributing to 2616 deaths) with the highest among the Mongol from East (PAF=65.1%, contributing to 763 deaths). Conclusion: The continuing increase of primary liver cancer among Mongol suggested further interventions were needed to combat its burden.     

Bronchoalveolar lavage fluid characteristics of early intermediate and late phases of ARDS

Objective: To determine the concentration of proteins and phospholipids, markers of inflammatory reaction such as platelet-activating factor (PAF), and cell alterations in bronchoalveolar lavage (BAL) fluid during the evolution of the acute respiratory distress syndrome (ARDS). Design: Prospective controlled study. Setting: 14-bed medical-surgical intensive care unit in a 750-bed university teaching hospital. Patients: 19 mechanically ventilated patients, 9 patients with ARDS and 10 patients without cardiopulmonary disease (controls), were eligible for this study. Interventions: BAL was performed during the early, intermediate, and late phases of ARDS. Measurements and results: Total phospholipids and individual phospholipid classes of the surfactant, proteins, PAF, and cells were measured. High levels of PAF, an increase in neutrophils and proteins, and quantitative as well as qualitative alterations in phospholipids in BAL fluid were observed in ARDS patients compared to the control group. PAF, proteins, and neutrophils were higher in early ARDS than in intermediate or late ARDS. The surfactant pool increased in the early phase and decreased in the intermediate or late phase of the syndrome. The qualitative alterations of surfactant consist of reduced phospholipid content in the surfactant structures with good surface properties; moreover, there was a considerable decrease in the percentage of phosphatidylcholine and phosphatidylglycerol, followed by an increase in phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, and sphingomyelin in all three phases of ARDS compared to the control group. Lyso-phosphatidylcholine was detectable only in late ARDS. Conclusion: Total surfactant phospholipids, surfactant components, and inflammatory markers such as PAF, cells, and proteins were affected in patients with ARDS. These factors, undergoing quantitative alterations during the course of ARDS, could have a significant role in the pathogenesis and evolution of ARDS. Received: 8 July 1997 Accepted: 17 December 1997     

The effect of platelet activating factor antagonist (BN 52021) on acute experimental pancreatitis with reference to multiorgan oxidative stress

Summary Acute hemorrhagic pancreatitis was induced in Wistar rats using a retrograde intraductal injection of 5% Na-taurocholate. Rats were treated with platelet-activating factor receptor (PAF) antagonist—BN 52021 (5 mg/kg) and sacrificed at 1 and 3 h after induction of acute pancreatitis. Malondialdehyde and sulfhydryl groups concentration were measured in pancreatic, lung, and liver tissue as a parameters of oxidant-antioxidant balance. We have shown that BN 52021 exerts only partial protecting effect against Na-TC-induced AP in rats. The positive effects of BN 52021 were expressed by: (1) Significant reduction of hyperamylasemia accompanied by lower malondialdehyde accumulation in pancreatic tissue; (2) Prevention of sulfl hydryl groups depletion in lung tissue; (3) Diminution of necrotic and inflammatory changes in pancreatic tissue; and (4) Improvement of survival rate. We suggest that these effects may depend on the inhibition of PAF-mediated activation and oxidant generation by phagocytes.     

Hypoxia induces a lipogenic cancer cell phenotype via HIF1α-dependent and -independent pathways

The biochemistry of cancer cells diverges significantly from normal cells as a result of a comprehensive reprogramming of metabolic pathways. A major factor influencing cancer metabolism is hypoxia, which is mediated by HIF1α and HIF2α. HIF1α represents one of the principal regulators of metabolism and energetic balance in cancer cells through its regulation of glycolysis, glycogen synthesis, Krebs cycle and the pentose phosphate shunt. However, less is known about the role of HIF1α in modulating lipid metabolism. Lipids serve cancer cells to provide molecules acting as oncogenic signals, energetic reserve, precursors for new membrane synthesis and to balance redox biological reactions. To study the role of HIF1α in these processes, we used HCT116 colorectal cancer cells expressing endogenous HIF1α and cells in which the hif1α gene was deleted to characterize HIF1α-dependent and independent effects on hypoxia regulated lipid metabolites. Untargeted metabolomics integrated with proteomics revealed that hypoxia induced many changes in lipids metabolites. Enzymatic steps in fatty acid synthesis and the Kennedy pathway were modified in a HIF1α-dependent fashion. Palmitate, stearate, PLD3 and PAFC16 were regulated in a HIF-independent manner. Our results demonstrate the impact of hypoxia on lipid metabolites, of which a distinct subset is regulated by HIF1α.     

A platelet-activating factor (PAF) receptor deficiency exacerbates diet-induced obesity but PAF/PAF receptor signaling does not contribute to the development of obesity-induced chronic inflammation

Platelet-activating factor (PAF) is a well-known phospholipid that mediates acute inflammatory responses. In the present study, we investigated whether PAF/PAF receptor signaling contributed to chronic inflammation in the white adipose tissue (WAT) of PAF receptor-knockout (PAFR-KO) mice. Body and epididymal WAT weights were higher in PAFR-KO mice fed a high-fat diet (HFD) than in wild-type (WT) mice. TNF-α mRNA expression levels in epididymal WAT and the infiltration of CD11c-positive macrophages into epididymal WAT, which led to chronic inflammation, were also elevated in HFD-fed PAFR-KO mice. HFD-fed PAFR-KO mice had higher levels of fasting serum glucose than HFD-fed WT mice as well as impaired glucose tolerance. Although PAF receptor signaling up-regulated the expression of TNF-α and lipopolysaccharide induced the expression of acyl-CoA:lysophosphatidylcholine acyltransferase 2 (LPCAT2) mRNA in bone marrow-derived macrophages, no significant differences were observed in the expression of LPCAT2 mRNA and PAF levels in epididymal WAT between HFD-fed mice and normal diet-fed mice. In addition to our previous finding in which energy expenditure in PAF receptor (PAFR)-deficient mice was low due to impaired brown adipose tissue function, the present study demonstrated that PAF/PAF receptor signaling up-regulated the expression of Ucp1 mRNA, which is essential for cellular thermogenesis, in 3T3-L1 adipocytes. We concluded that the marked accumulation of abdominal fat due to HFD feeding led to more severe chronic inflammation in WAT, which is associated with glucose metabolism disorders, in PAFR-KO mice than in WT mice, and PAF/PAF receptor signaling may regulate energy expenditure and adiposity.     

MK2 plays an important role for the increased vascular permeability that follows thermal injury

We previously reported Rho kinase is involved in vessel hyper-permeability caused by burns. Here we further explore the Rho kinase downstream signaling, it is found that its specific inhibitor Y27632 significantly diminishes the activation of JNK and p38 MAPKs but not ERK that induced by serum from burned rats (burn-serum). JNK activation was found involved in the expression of HUVEC adhesion molecules following thermal injury, although not in the process of stress fiber formation. Inhibition of various MAPKs by specific inhibitors showed that SB203580 (inhibitor of p38), but neither SP600125 (inhibitor of JNK) nor PD98059 (inhibitor of ERK), abolish activation of the p38 downstream kinase MK2. Demonstration of stress fibers by fluorescent-labeled phalloidin showed that inhibition of MK2, either by its specific inhibitor or by dominant negative adeno-viral-carried constructs, significantly reduced burn-serum-induced HUVEC stress-fiber formation, while inhibition of another downstream p38 MAPK kinase, PRAK, had no such effects. Transfection of dominant negative adeno-viral MK2 (Ad-MK2(A)) significantly inhibited thermal injury-induced blood vessel hyper-permeability in rats and, moreover, prolonged the survival of burned rats beyond 72 h following thermal injury. One of the mechanisms behind these phenomena is that Ad-MK2(A) causes a significant depression of burn-serum-induced HSP27-phosphorylation, while the adeno-viral transported dominant negative PRAK (Ad-PRAK(A)) does not block. Although the effect of blockade of MK2 through its adeno-viral approach requires further study and investigation of alternatives to know for sure, we may have found a new pathway behind thermal-injury-induced blood vessel hyper-permeability, namely: Rho kinase > p38 > MK2 > HSP27.     

房间隔起搏临床应用的体会

目的　探讨有适应症的阵发性房颤患者行永久房间隔起搏的可行性及有效性。方法　先行心内电生理标测 ,寻找使双心房同步激动的房间隔最佳起搏点 ,采用主动固定起搏导线固定于该部位。结果　 4例患者窦性心律时房间传导为 10 6 0± 4 3ms ,标测后房间隔起搏房间传导时间为 11 0± 1 1ms,(P <0 0 0 1)。达到了双心房同步起搏。 3例患者成功地植入房间隔主动固定导线 ,一例患者失败。结论　永久房间隔起搏方法在伴有房间传导阻滞的阵发性房颤患者中的应用是安全可行的。