开窗减压术与传统刮治术治疗颌骨囊肿的手术效果、生活质量和预后的对比研究

目的:对比颌骨囊肿经传统刮治术与开窗减压术治疗后的手术效果、生活质量和预后。方法:回顾性选取2016年1月～2018年7月期间我院收治的90例颌骨囊肿患者的临床资料,上述患者根据手术方式的不同分为A组(n=45,传统刮治术)和B组(n=45,开窗减压术),比较两组患者疗效、临床指标、生活质量和预后。结果:B组患者临床总有效率为97.78%(44/45),高于A组的84.44%(38/45)(P0.05)。B组患者伤口愈合时间、手术时间、均短于A组,术中出血量少于A组(P0.05)。两组患者末次随访时情绪、外貌、味觉、疼痛、唾液、咀嚼等项目评分均升高,且B组高于A组(P0.05)。B组并发症发生率、复发率均低于A组(P0.05)。结论:与传统刮治术治疗相比,开窗减压术治疗颌骨囊肿,在手术效果、生活质量和预后方面效果显著,具有较高的临床应用价值。     

微血管减压术联合感觉根部分切断术对原发性三叉神经痛患者疼痛评分、生活质量及睡眠状况的影响

目的:探讨微血管减压术(MVD)联合感觉根部分切断术(PSR)对原发性三叉神经痛(TN)患者疼痛评分、生活质量及睡眠状况的影响。方法:回顾性分析2015年2月~2019年3月期间我院收治的80例原发性TN患者的临床资料,根据手术方式的不同将患者分为对照组(n=40,MVD治疗)和研究组(n=40,MVD联合PSR治疗),比较两组患者疼痛评分、生活质量、围术期指标、睡眠状况、并发症发生情况以及复发率。结果:两组患者治疗后视觉疼痛模拟量表(VAS)评分均较治疗前下降,且研究组低于对照组(P<0.05)。两组患者治疗后生活质量量表(SF-36)各维度评分均较治疗前升高,且研究组高于对照组(P<0.05)。两组患者治疗后匹兹堡睡眠质量指数表(PSQI)各项目评分均较治疗前升高,且研究组高于对照组(P<0.05)。研究组住院时间短于对照组,手术时间长于对照组(P<0.05);两组术中出血量比较无统计学差异(P>0.05)。研究组的并发症总发生率低于对照组(P<0.05)。两组随访期间复发率比较差异无统计学意义(P>0.05)。结论:MVD联合PSR治疗原发性TN,虽然手术时间较长,但是在减轻患者疼痛、改善患者生活质量及睡眠状况等方面效果显著,能够降低并发症发生率。     

How calcium signals in myocytes and pericytes are integrated across in situ microvascular networks and control microvascular tone

The microcirculation is the site of gas and nutrient exchange. Control of central or local signals acting on the myocytes, pericytes and endothelial cells within it, is essential for health. Due to technical problems of accessibility, the mechanisms controlling Ca²⁺ signalling and contractility of myocytes and pericytes in different sections of microvascular networks in situ have not been investigated. We aimed to investigate Ca²⁺ signalling and functional responses, in a microcirculatory network in situ. Using live confocal imaging of ureteric microvascular networks, we have studied the architecture, morphology, Ca²⁺ signalling and contractility of myocytes and pericytes. Ca²⁺ signals vary between distributing arcade and downstream transverse and precapillary arterioles, are modified by agonists, with sympathetic agonists being ineffective beyond transverse arterioles. In myocytes and pericytes, Ca²⁺ signals arise from Ca²⁺ release from the sarcoplasmic reticulum through inositol 1,4,5-trisphosphate-induced Ca²⁺ release and not via ryanodine receptors or Ca²⁺ entry into the cell. The responses in pericytes are less oscillatory, slower and longer-lasting than those in myocytes. Myocytes and pericytes are electrically coupled, transmitting Ca²⁺ signals between arteriolar and venular networks dependent on gap junctions and Ca²⁺ entry via L-type Ca²⁺ channels. Endothelial Ca²⁺ signalling inhibits intracellular Ca²⁺ oscillations in myocytes and pericytes via L-arginine/nitric oxide pathway and intercellular propagating Ca²⁺ signals via EDHF. Increases of Ca²⁺ in pericytes and myocytes constrict all vessels except capillaries. These data reveal the structural and signalling specializations allowing blood flow to be regulated by myocytes and pericytes.     

Evidence that NO/cGMP/PKG signalling cascade mediates endothelium dependent inhibition of IP3R mediated Ca2+ oscillations in myocytes and pericytes of ureteric microvascular network in situ

In ureteric microvessels the antagonistic relationship between Ca²⁺ signalling in endothelium and Ca²⁺ oscillations in myocytes and pericytes of arterioles and venules involves nitric oxide (NO), but the underlying mechanisms are not well understood. In the present study we investigated the effects of carbachol and NO donor SNAP on Ca²⁺ signalling and vasomotor responses of arterioles and venules in intact urteric microvascular network in situ using confocal microscopy. Vasomotor responses of arterioles and venules induced by AVP correlated with the occurrence of Ca²⁺ oscillations in the myocytes and pericytes and were not abolished by the removal of Ca²⁺ from extracellular fluid. Carbachol-induced rise of intracellular Ca²⁺ in endothelium was accompanied by the termination of the Ca²⁺ oscillations in myocytes and pericytes. This carbachol-induced inhibitory effect on Ca²⁺ oscillations in myocytes and pericytes was reversed by ODQ, an inhibitor of soluble guanylyl cyclase (sGC) and by Rp-8-pCPT-cGMPS, an inhibitor of protein kinase G (PKG). Ca²⁺ oscillations in myocytes and pericytes were also effectively blocked by NO donor SNAP. An Inhibitory effect of SNAP was markedly enhanced by zaprinast, a selective inhibitor of cGMP-specific phosphodiesterase-5, and reversed by sGC inhibitor, ODQ and PKG inhibitor, Rp-8-pCPT-cGMPS. The cGMP analogue and selective PKG activator 8pCPT-cGMP also induced inhibition of the AVP-induced Ca²⁺ oscillations in myocytes and pericytes. SNAP had no effects on Ca²⁺ oscillations induced by caffeine in distributing arcade arterioles. Consequently, we conclude that NO- mediated inhibition of Ca²⁺ oscillations in myocytes and pericytes predominantly recruits the cGMP/PKG dependent pathway. The inhibitory effect of NO/cGMP/PKG cascade is associated with suppressed Ca²⁺ release from the SR of myocytes and pericytes selectively via the inositol triphosphate receptor (IP₃R) channels.     

ERM蛋白在微血管内皮细胞通透性调控中的研究进展

埃兹蛋白(Ezrin)/根蛋白(Radixin)/膜突蛋白(Moesin)(ERM)是细胞膜与胞内骨架的连接蛋白,具有高度同源性。细胞外刺激因子可通过多种信号通路磷酸化ERM蛋白,使细胞骨架重构,从而调控微血管内皮细胞通透性,在感染、炎症、代谢异常等病理过程中发挥作用。ERM功能调节的一个重要环节就是其羧基末端苏氨酸残基磷酸化后引起ERM构象的改变,暴露的羧基末端尾部的肌动蛋白(actin)-细胞骨架结合位点;故通过ERM的桥接作用,可将肌动蛋白微丝与细胞膜相连,使血管内皮细胞屏障功能发生变化。目前已知能使ERM磷酸化的激酶有蛋白激酶C(PKC)、促分裂原活化蛋白激酶(MAPK)、Rho相关激酶(ROCK),分别通过p38-MAPK、Rho/ROCK、PKC信号通路参与微血管内皮屏障功能的调控。本文旨在阐述ERM及其相关信号通路在微血管内皮细胞通透性调控中发挥的作用。     

根据退行性脊柱侧凸患者症状选择不同手术方案的临床研究

目的:探究根据退行性脊柱侧凸患者症状选择不同手术方案的治疗效果。方法:随机选取我院2007年9月到2015年10月收治的退行性脊柱侧凸患者124例,根据症状不同分A组和B组。A组62例患者腰背痛,接受长节段矫形内固定术;B组62例患者下肢症状明显,接受责任节段减压内固术。治疗期间记录两组手术时间、术中出血量、固定节段数及腰前凸角度,于治疗前、治疗后1个月以及末次随访时腰椎侧凸处的Cobb角,并采用视觉模拟评分法(VAS)和Oswestry功能障碍指数(ODI)评价患者疗效。结果:A组手术时间、出血量、固定节段数及腰前凸角度显著高于B组(P0.05);治疗后和末次随访两组患者VAS评分、ODI指数及Cobb角均有明显好转(P0.05),两组治疗后和末次随访之间的差异无统计学意义(P0.05)。结论:退行性脊柱侧凸在治疗时需根据患者具体症状选择不同的手术方案,长节段矫形内固定术耗时长、术中出血量多,在治疗时应谨慎,预防相关并发症的发生。     

Magnetic resonance imaging based modeling of microvascular perfusion in patients with peripheral artery disease

Peripheral artery disease (PAD) is associated with an increased risk of adverse cardiovascular events, impaired lower extremity blood flow and microvascular perfusion abnormalities in the calf muscles which can be determined with contrast-enhanced magnetic resonance imaging (CE-MRI). We developed a computational model of the microvascular perfusion in the calf muscles. We included 20 patients (10 PAD, 10 controls) and utilized the geometry, mean signal intensity and arterial input functions from CE-MRI calf muscle perfusion scans. The model included the microvascular pressure (p_v), outflow filtration coefficient (OFC), transfer rate constant (k^t), porosity (φ), and the interstitial permeability (K_tissue). Parameters were fitted and the simulations were compared across PAD patients and controls. Intra-observer reproducibility of the simulated mean signal intensities was excellent (intraclass correlation coefficients >0.995). k^t and K_tissue were higher in PAD patients compared with controls (4.72 interquartile range (IQR) 3.33, 5.56 vs. 2.47 IQR 2.10, 2.85; p = 0.003; and 3.68 IQR 3.18, 4.41 vs. 1.81 IQR 1.81, 1.81; p < 0.001). Conversely, porosity (φ) was lower in PAD patients compared with controls (0.52 IQR 0.49, 0.54 vs. 0.61 IQR 0.58, 0.64; p = 0.016). Porosity (φ) was correlated with the ankle brachial index (r = 0.64, p = 0.011). The proposed computational microvascular model is robust and reproducible, and essential model parameters differ significantly between PAD patients and controls.     

Involvement of tachykinin NK(1) and NK(2) receptors in changes in lung mechanics and airway microvascular leakage during the early phase of endotoxemia in Guinea pigs

We investigated the role of tachykinins in airway neurogenic responses occurring in the early phase of endotoxemia. Forty-eight anesthetized guinea pigs were evenly divided into six groups pretreated with either saline vehicle, CP-96,345 (a tachykinin NK(1) receptor antagonist), SR-48,968 (a tachykinin NK(2) receptor antagonist) or CP-96,345 and SR-48,968 in combination. Animals then received an intravenous injection of either saline (the vehicle for endotoxin) or endotoxin (30 mg/kg). Total lung resistance (R(L)) and dynamic lung compliance (C(dyn)) were continuously measured before and 30 min after administration of saline or endotoxin. Airway microvascular leakage was assessed at the end of the observation period. Endotoxin significantly increased R(L) and decreased C(dyn) 10 min after intravenous endotoxin injection. Plasma extravasation significantly increased in the trachea, main bronchi and intrapulmonary airways with endotoxin administration. These changes in lung mechanics were abolished by SR-48,968, but were unaffected by CP-96,345. The plasma extravasation was largely attenuated by CP-96,345 and/or SR-48,968. We conclude that (1) endogenous tachykinins play an important role in producing changes in lung mechanics and airway microvascular leakage during the early phase of endotoxemia and (2) activation of tachykinin NK(2) receptors is responsible for the former response, while activation of both tachykinin NK(1) and NK(2) receptors is involved in the latter response.     

竹红菌素光敏剂与微血管病变光动力治疗

光动力疗法已被用于临床治疗除实体肿瘤以外的一些微血管类疾病,包括鲜红斑痣(portwine stains,PWS)和老年视网膜黄斑变性(age-related macular degeneration,AMD)等。竹红菌素是一种苝醌类光敏剂,因为在光疗窗口(600～900 nm)的吸收较少,它不适用于实体肿瘤的光动力治疗,但对于治疗微血管类疾病却有其独特的优势。本文根据竹红菌素光物理特性提出其主要适应症范围,并根据其临床实用化问题提出应对策略。通过构造竹红菌素水溶性纳米制剂或具有优化脂水双亲性的衍生物,实现脂溶性光敏剂既可以安全给药又最大程度保持生物利用度和光动力活性。生物学实验证明竹红菌素类光敏剂对生物靶体具有超强的光动力活性。由此推测:竹红菌素类光敏剂在光动力治疗微血管疾病(如鲜红斑痣和老年黄斑变性)及其它浅表型疾病方面具有广阔的应用前景。     

Plasmalemmal vacuolar H+-ATPases in angiogenesis, diabetes and cancer

Angiogenesis, i.e., new blood vessel formation, is required in normal and pathological states. A dysfunction in the microvascular endothelium occurs in diabetes, leading to decreased blood flow and limb amputation. In cancer, angiogenesis is increased to allow for growth, invasion, and metastasis of tumor cells. Better understanding of the molecular events that cause or are associated with either of these diseases is needed to develop therapies. The tumor and angiogenic cells micro-environment is acidic and not permissive for growth. We have shown that to survive this environment, highly metastatic and angiogenic cells employ vacuolar H⁺-ATPase at their plasma membranes (pmV-ATPases) to maintain an alkaline pH^cyt. However, in lowly metastatic and in microvascular endothelial cells from diabetic model, the density of pmV-ATPase and the cell invasiveness are decreased. Therefore, the overexpression of the pmV-ATPase is important for cell invasion, and essential for tumor progression, angiogenesis and metastasis. Both, cancer and diabetes are heterogenous diseases that involve many different proteins and signaling pathways. Changes in pH^cyt have been associated with the regulation of a myriad of proteins, signaling molecules and pathways affecting many if not all cellular functions. Since changes in pH^cyt are pleiotropic, we hypothesize that alteration in a single protein, pmV-ATPase, that can regulate pH^cyt may explain the dysfunction of many proteins and cellular pathways in diabetes and cancer. Our long term goal is to determine the molecular mechanisms by which pmV-ATPase expression regulates tumor angiogenesis and metastasis. Such knowledge would be useful to identify targets for cancer therapy.