超声造影定量分析联合血清AFP、VEGFR-2、sTim-3对原发性肝癌TACE治疗疗效的预测价值

摘要 目的：探讨超声造影定量分析联合血清甲胎蛋白（AFP）、血管内皮生长因子受体-2（VEGFR-2）、可溶性T细胞免疫球蛋白粘蛋白分子3（sTim-3）对原发性肝癌肝动脉化疗栓塞（TACE）治疗疗效的预测价值。方法：选择2020年1月至2022年10月海军军医大学第二附属医院收治的原发性肝癌患者94例。行TACE治疗2个月,采用改良的实体瘤疗效评价标准评估患者疗效,根据不同疗效分为疗效不良组（n=32）和疗效良好组（n=62）。所有患者均行超声造影检查,比较两组超声造影定量分析参数、治疗前血清AFP、VEGFR-2、sTim-3水平,采用受试者工作特征（ROC）曲线分析超声造影定量分析参数联合血清AFP、VEGFR-2、sTim-3对原发性肝癌TACE治疗疗效的预测价值。结果：经TACE治疗,62例患者疗效良好、32例患者疗效不良,治疗有效率为65.96%。疗效良好组术前超声造影达峰时间、等增强开始时间显著长于疗效不良组（P<0.05）。疗效良好组术前血清AFP、VEGFR-2、sTim-3水平显著低于疗效不良组（P<0.05）。ROC曲线分析结果显示,超声造影定量分析联合血清AFP、VEGFR-2、sTim-3对原发性肝癌TACE治疗疗效预测的曲线下面积（AUC）为0.950,灵敏度为84.85%,特异度为82.12%,高于各指标单独检测。结论：超声造影定量分析参数、血清AFP、VEGFR-2、sTim-3水平可预测原发性肝癌患者TACE治疗的疗效,且联合诊断的预测效能更高。     

Systolic Blood Pressure is Related to Catecholamine Sensitivity in Subcutaneous Abdominal Fat Cells

A relationship between abdominal obesity and hypertension is well established. In search for an early-onset defect in adipocyte function linking these two conditions, we compared catecholamine sensitivity in subcutaneous abdominal fat cells with 24-hour systolic, mean arterial and diastolic blood pressure in 16 healthy, normotensive subjects. Clear inter-individual variations in the adipocyte lipolytic adrenoceptor sensitivity (pD₂) for noradrenaline were observed in dose-response experiments (i.e., about 4 log units). An inverse and independent correlation was found between the 24-hour systolic blood pressure and pD₂ for noradrenaline (r = ?0.67, p < 0.01). The mean arterial blood pressure was also negatively correlated to peripheral noradrenaline sensitivity (r = ?0.58, p < 0.05). However, no significant relationship between the 24-hour diastolic blood pressure and pD₂ for noradrenaline was demonstrated. In conclusion we suggest that catecholamine resistance in subcutaneous fat cells may be associated with autonomic dysfunction and impaired blood pressure regulation. This finding is supported by the fact that both noradrenaline sensitivity and 24-hour systolic blood pressure also are correlated to the individual orthostatic heart rate responses, reflecting the sympathetic nervous system tone (r=0.61, p=0.01 and r= ?0.53, p=0.03, respectively). The relationship between noradrenaline sensitivity and systolic blood pressure may be of importance in the early development of hypertension in man.     

Tachykinin NK-1 receptor probed with constrained analogues of substance P

The action of rotameric probes introduced either in position 7 or 8 in the sequence of substance P (SP) was investigated, i.e. -tetrahydroisoquinoleic acid (Tic), -fluorenylglycine (Flg), -diphenylalanine (Dip), the diastereoisomers of -1-indanylglycine (Ing) and -benz[ƒ]indanylglycine (Bfi), the Z- and E-isomers of dehydrophenylalanine and dehydronaphthylalanine (Δ^ZPhe, Δ^EPhe, Δ^ZNal, Δ^ENal) and (Dmp). The aim of this study was the topographical characterization of the binding subsites of human NK-1 receptor expressed in CHO cells, especially the S₇ and S₈ subsites, corresponding to residues Phe⁷ and Phe⁸ of substance P. According to the binding potencies of these substituted-SP analogues, the S₇ binding subsite is smaller than the S₈ subsite: the S₇ subsite accepts only one aromatic nucleus, while the S₈ can accommodate three coplanar nuclei altogether. These findings are compatible with the idea that the S₈ binding subsite may reside in the extracellular loops of the hNK-1 receptor. NK-1 agonists bind to human NK-1 receptor and activate the production of both inositol phosphates and cyclic AMP. As already quoted for septide, [pGlu⁶, Pro⁹]SP(6–11), discrepancies are observed between affinity (K_i) and activity (EC₅₀) values for IPs production. While a weak correlation between K_i and EC₅₀ values for IPs production could be found (r = 0.70), an excellent correlation could be demonstrated between their affinities (K_i) and their potencies (EC₅₀) for cAMP production (r = 0.97). The high potency (EC₅₀) observed for ‘septide-like’ molecules on PI hydrolysis, compared to their affinity is not an artefact related to the high level of NK-1 receptors expressed on CHO cells since a good correlation was found between EC₅₀ values obtained for PI hydrolysis and those measured for spasmogenic activity in guinea pig ileum bioassay (r = 0.94).

According to the binding potencies of constrained analogues of phenylalanine, the S₇ binding subsite of human NK-1 receptor is small, whereas the S₈, which can accommodate three coplanar nuclei, might probably reside in the extracellular loop. The discrepancies observed between affinity (K_i) and activity (EC₅₀) values for IPs production are not an artefact of CHO cells since a good correlation was found between EC₅₀ for PI hydrolysis and those measured in guinea pig ileum bioassay.     

高压静电场处理沙棘插条生根状况的初步研究

用高压静电场处理沙棘插条研究生根状况,方法简便易于处理,该装置适于进行大规模的处理,从目前研究表明：高压静电场对沙棘插条有正刺激效应,并以电场强度为３．９ｋｖ／ｃｍ,时间为４０分钟处理最佳。     

A comparative study of the effects of iloprost and PGE1 on pulmonary arterial pressure and edema formation in the isolated perfused rat lung model

Isolated lungs from male Wistar rats (250–350 g) were perfused at a constant flow rate (10 ml/min, non -recirculating) with Krebs-Ringerbicarbonate buffer containing 4.5 % bovine serum albumin, and were ventilated at a positive pressure (60 breaths/min). Pulmonary arterial pressure and lung weight (as a measure of edema formation) were recorded continuously. After an equilibration period of 20 minutes the various test compounds were added to the perfusion fluid and experimental recording was continued for another 60 minutes.The effects of the stable PGI₂-mimetic, iloprost, of PGE₁, and of the biologically active PGE₁-metabolite, 13,14-dihydro-PGE,, were evaluated in this model (n=6). Iloprost showed slight, but not significant vasodilation; however, lung weight remained unchanged. PGE₁ and 13,14-dihydro-PGE₁ also caused slight vasodilation, but in contrast to iloprost these compounds induced distinct pulmonary edema. The lung weight gain was discernible at concentrations of 2.8 × 10^-6 mol/1 (significant at 2.8 × 10^-5 mol/l; p 0.05) and was accompanied by increases in the wet-weight to dry-weight ratios. These findings were duplicated in a second set of experiments (n = 6) from which the same results were obtained.The results indicate that at high concentrations PGE, (and 13,14-dihydro-PGE₁), but not iloprost, can induce pulmonary edema in rats probably by increasing the permeability of the pulmonary vasculature.     

Cell wall synthesis in cotton roots after infection with Fusarium oxysporum

Fusarium oxysporum f. sp. vasinfectum penetration hyphae infect living cells in the meristematic zone of cotton (Gossypium barbadense L.) roots. We characterized wall modifications induced by the fungus during infection of the protodermis using antibodies against callose, arabinogalactan-proteins, xyloglucan, pectin, polygalacturonic acid and rhamnogalacturonan I in high-pressure frozen, freeze-substituted root tissue. Using quantitative immunogold labelling we compared the cell walls before and after hyphal contact, cell plates with plasmodesmata during cytokinesis, and wall appositions induced by fungal contact. In the already-existing wall, fungal contact induced only minor modifications such as an increase of xyloglucan epitopes. Wall appositions mostly exhibited epitopes similar to the cell plate except that wall appositions had a much higher callose content. This study shows that wall appositions induced by Fusarium oxysporum hyphae are the result of normal cell wall synthesis and the addition of large amounts of callose. The appositions do not stop fungal growth.     

Enhanced thermotolerance by hydrostatic pressure in the deep-sea hyperthermophile Pyrococcus strain ES4

Abstract: The combined effect of hydrostatic pressure and heat shock on thermotolerance was examined in the deep-sea hyperthermophilic archaeon Pyrococcus strain ES4. Pressure equivalent to the depth of isolation (22 MPa) enhanced ES4's survival at super-optimal temperatures (101–108°C) relative to low pressure (3 MPa). Pressure also raised the temperature at which a putative heat-shock protein (98 kDa) accumulated. ES4 grown at 95°C and 3 MPa displayed immediate enhanced thermotolerance to 105°C after being shifted to 22 MPa. Cultures grown at 95°C and 22 MPa and then heat shocked at 105°C and 3 MPa retained enhanced thermotolerance after decompression. These results suggest that this deep-sea hyperthermophile has developed pressure-induced responses that include increased survival to hyperthermal conditions.     

Characterization of mechanosensitive channels in Escherichia coli cytoplasmic membrane by whole-cell patch clamp recording

Whole-cell patch clamp recordings were done on giant protoplasts of Escherichia coli. The pressure sensitivity of the protoplasts was studied. Two different unit conductance mechanosensitive channels, 1100 ± 25 pS and 350 ± 14 pS in 400 mm symmetric KCl solution, were observed upon either applying positive pressure to the interior of the cells or down shocking the cells osmotically. The 1100 pS conductance channel discriminated poorly among the monovalent ions tested and it was permeable to Ca²⁺ and glutamate^?. Both of the two channels were sensitive to the osmotic gradient across the membrane; the unit conductances of the channels remained constant while the mean current of the cell was increased by increasing the osmotic gradient. Both of the channels were voltage sensitive. Voltage-ramp results showed that the pressure sensitivity of protoplasts was voltage dependent: there were more channels active upon depolarization than hyperpolarization. The mech anosensitive channels were reversibly blocked by gadolinium ion. Also they could reversibly be inhibited by protons. Mutations in two of the potassium efflux systems, KefB and KefC, did not affect the channel activity, while a null mutation in the gene for KefA changed the channel activity significantly. This indicates a potential modulation of these channels by KefA.