原发性肝癌诊疗规范(2019年版)

1概述原发性肝癌是目前我国第4位常见恶性肿瘤及第2位肿瘤致死病因,严重威胁我国人民的生命和健康[1-2]。原发性肝癌主要包括肝细胞癌(hepatocellular carcinoma,HCC)、肝内胆管癌(intrahepatic cholangiocarcinoma,ICC)和HCC-ICC混合型3种不同病理学类型。3者在发病机制、生物学行为、组织学形态、治疗方法以及预后等方面差异较大,其中HCC占85%~90%。本规范中的“肝癌”指HCC。     

Fibrinogen γ chain functions

Summary.  This review covers the functional features of the fibrinogen γ chains including their participation in fibrin polymerization and cross-linking, their role in the initiation of fibrinolysis, their binding and regulation of factor XIII activity, their interactions with platelets and other cells, and their role in mediating thrombin binding to fibrin, a thrombin inhibitory function termed 'antithrombin I'.     

Treatment with β‐blockers—the value of an even plasma concentration over 24 h

The aim of this paper was to examine if there were clinical studies supporting a beneficial effect of an even plasma concentration over 24 h for the most frequently prescribed β 1‐blockers in clinical practice, metoprolol CR/ZOK and atenolol. There are several studies showing that metoprolol CR/ZOK has a more even plasma concentration compared with atenolol and conventional metoprolol tablets when administered once daily. There are also studies showing that metoprolol CR/ZOK produces a more even β 1‐blockade over 24 h. This is determined by expressing the percentage reduction in exercise heart rate in relation to placebo at intervals throughout the 24‐h period and comparing the results with those of atenolol and conventional metoprolol tablets. Clinical studies indicate that the low peak plasma concentration produced by metoprolol CR/ZOK leads to more β 1 selectivity than atenolol and conventional metoprolol tablets. The loss of β 1 selectivity at peak plasma concentrations may cause unwanted side‐effects. The peak plasma concentration of atenolol coincides with increased general and leg fatigue, problems less evident when patients are on metoprolol CR/ZOK. The frequency and severity of other central nervous system related side‐effects are comparable with metoprolol CR/ZOK and atenolol. In conclusion, there are several clinical studies supporting a beneficial effect of the even plasma concentration over 24 h achieved with metoprolol CR/ZOK.     

β-adrenoceptor blockade and migraine

Except for propranolol, no other Beta-blocker has been studied thoroughly in the prophylaxis of migraine. Of those studied, propranolol, atenolol and timolol were shown to be useful in double-blind clinical trials. The mode, or even the site of action of these drugs in unknown. Possible mechanisms of action are peripheral vascular effects, a central action, 5-HT antagonism, an anxiolytic effect and a multifactorial action. The only common property of the successful drugs is lack of partial agonist activity and their profiles do not fully support any of the above hypotheses. Trials of drugs in the prophylaxis of migraine have in general been unsatisfactory due to the difficulty in controlling many variables. Beta-blockers with differing properties offer an opportunity to define the properties necessary for anti-migraine activity and perhaps shed light on the pathogenesis of migraine.     

β-BLOCKERS and BLOOD SUGARS

Catecholamines mediate sympathetic activity throughout the body and, since carbohydrate metabolism is under sympathetic control they influence the availability of glucose for utilization as energy. They achieve this by modifying the response to a raised blood sugar by either suppressing insulin release, an a-receptor stimulant effect, or by promoting insulin release, probably a β₂ stimulant effect. When the blood sugar falls, catecholamines initiate metabolic processes which increase blood glucose and restore it to normal. This is also thought to be a β₂-receptor stimulant effect. It would therefore be expected that drugs which blocked β-adrenoreceptors would interfere with both the insulin release which occurs during hyperglycaemia and the glycogenosis and gluconeogenesis which occur in response to a fall in blood sugar. Both of these actions have been demonstrated in acute studies usually in volunteers. The clinical relevance of these effects remains to be determined though some guidelines can be suggested on the basis of data currently available, and are given at the end of the paper.     

tBuOK-triggered bond formation reactions

Recently, inexpensive and readily available tBuOK has seen widespread use in transition-metal-free reactions. Herein, we report the use of tBuOK for S–S, S–Se, N N and C N bond formations, which significantly extends the scope of tBuOK in chemical synthesis. Compared with traditional methods, we have realized mild and general methods for disulfide, azobenzenes imine etc. synthesis.

Inexpensive and readily available ^tBuOK can trigger a series of bond formation reactions, including S–S, S–Se, Se–Se, and N N and C N bonds.     

Empiric Therapy with β-Blockers

The only class of drugs with significant effects on ventricular fibrillation and sudden death in humans is that of β-blockers. The exact mechanisms for these prophyiactic effects are not knotvn but may be related to both ontiischemic or anliarrhythmic infiuences. It seems reasonable to suggest that one should use a β-blocker with proven effect on total mortality and sudden cardiac death after myocardial infarction as prophylaxis. Therefore, propranolol, timolol. or metoprolol. should be instituted in order to improve prognosis when there are no conlraindications. In addition to possible effects on survival one would aiso expect to reduce the risk for new ischemic events with angina or reinfarction. In contrast, class I antiarrhythmic agents are useful for symptomatic ventricular arrhythmias but there is no proof for any effect on ventricular fibrillation and sudden cardiac death.     

Comparison of cell-surface TFPIα and β

BACKGROUND: Tissue factor pathway inhibitor (TFPI) is mainly produced by endothelial cells and alternative mRNA splicing generates two forms, TFPIalpha and TFPIbeta. A portion of expressed TFPI remains associated with the cell surface through both direct (TFPIbeta) and indirect (TFPIalpha) glycosylphosphatidyl-inositol (GPT)-mediated anchorage. OBJECTIVE: Compare the structure and properties of TFPIalpha and TFPIbeta. METHODS: TFPIalpha and TFPIbeta, with protein molecular masses of 36 and 28 kDa, respectively, migrate similarly (46 kDa) on SDS-PAGE. Experiments using specific glycosidases were carried out to determine the different glycosylation pattern of the two forms. ECV304 cells, a cell line with some endothelial properties, were stimulated with IL-lbeta, LPS, and TNFalpha for up to 24 hrs and mRNA levels and protein synthesis were determined. Stable clones of ECV304 cells that express reduced levels of TFPIalpha, TFPIbeta or both were produced using a plasmid-based small-interfering RNA technique. Surface TFPI activity was determined by a two-stage chromogenic assay based on the ability of each form to inhibit FXa activation by FVIIa on cells with comparable amount of tissue factor (TF). RESULTS AND CONCLUSIONS: The deglycosylation studies show that the difference in molecular masses is due to a greater degree of sialylation in O-linked carbohydrate in TFPIbeta. The mRNA and protein levels of neither form of TFPI were affected by stimulation of cells with inflammatory stimuli. Although TFPIalpha comprises 80% of the surface-TFPI, TFPIbeta was responsible for the bulk of the cellular FVIIa/TF inhibitory activity, suggesting a potential alternative role for cell surface TFPIalpha.