食管癌不同术式术后长期生活质量实验研究

目的:探讨食管癌传统开胸手术中不同术式对术后长期生活质量(QOL)影响。方法:回顾性调查2010年4月1日至2011年4月1日在我科例行传统开胸手术颈部吻合和胸内吻合的160食管癌患者,将其分为两组,A组:颈部吻合手术;B组:胸内吻合手术。采用生活质量测定量表核心量表(QLQ-C30),对其术前和术后3,6和12个月的QLQ-C30得分与参考值进行比较。结果:术后情绪功能,体力功能显着下降;症状方面,术后呼吸困难,疼痛明显加重;术后第3个月疲乏及经济困难明显加重;术后第12个月起,经济困难状况好转,较术前无明显差异;术后颈部吻合手术组较胸内吻合手术组在体力功能、角色功能、情绪功能及总体状况显著的降低;症状方面,颈部吻合手术组较胸内吻合手术组,术后疲乏显著升高,呼吸困难术后显著升高直至术后第12个月才基本恢复,无统计学差异。结论:术后生活质量与术前比较,颈部吻合对患者生活质量影响明显。比较两种方法,颈部吻合患者较胸内吻合患者术后长期生活质量下降明显。     

Regular bottlenecks and restrictions to somatic fusion prevent the accumulation of mitochondrial defects in Neurospora

The replication and segregation of multi-copy mitochondrial DNA (mtDNA) are not under strict control of the nuclear DNA. Within-cell selection may thus favour variants with an intracellular selective advantage but a detrimental effect on cell fitness. High relatedness among the mtDNA variants of an individual is predicted to disfavour such deleterious selfish genetic elements, but experimental evidence for this hypothesis is scarce. We studied the effect of mtDNA relatedness on the opportunities for suppressive mtDNA variants in the fungus Neurospora carrying the mitochondrial mutator plasmid pKALILO. During growth, this plasmid integrates into the mitochondrial genome, generating suppressive mtDNA variants. These mtDNA variants gradually replace the wild-type mtDNA, ultimately culminating in growth arrest and death. We show that regular sequestration of mtDNA variation is required for effective selection against suppressive mtDNA variants. First, bottlenecks in the number of mtDNA copies from which a ‘Kalilo’ culture started significantly increased the maximum lifespan and variation in lifespan among cultures. Second, restrictions to somatic fusion among fungal individuals, either by using anastomosis-deficient mutants or by generating allotype diversity, prevented the accumulation of suppressive mtDNA variants. We discuss the implications of these results for the somatic accumulation of mitochondrial defects during ageing.     

Rats with minimal hepatic encephalopathy show reduced cGMP-dependent protein kinase activity in hypothalamus correlating with circadian rhythms alterations

Patients with liver cirrhosis show disturbances in sleep and in its circadian rhythms which are an early sign of minimal hepatic encephalopathy (MHE). The mechanisms of these disturbances are poorly understood. Rats with porta-caval shunt (PCS), a model of MHE, show sleep disturbances reproducing those of cirrhotic patients. The aims of this work were to characterize the alterations in circadian rhythms in PCS rats and analyze the underlying mechanisms. To reach these aims, we analyzed in control and PCS rats: (a) daily rhythms of spontaneous and rewarding activity and of temperature, (b) timing of the onset of activity following turning-off the light, (c) synchronization to light after a phase advance and (d) the molecular mechanisms contributing to these alterations in circadian rhythms. PCS rats show altered circadian rhythms of spontaneous and rewarding activities (wheel running). PCS rats show more rest bouts during the active phase, more errors in the onset of motor activity and need less time to re-synchronize after a phase advance than control rats. Circadian rhythm of body temperature is also slightly altered in PCS rats. The internal period length (tau) of circadian rhythm of motor activity is longer in PCS rats. We analyzed some mechanisms by which hypothalamus modulate circadian rhythms. PCS rats show increased content of cGMP in hypothalamus while the activity of cGMP-dependent protein kinase was reduced by 41% compared to control rats. Altered cGMP-PKG pathway in hypothalamus would contribute to altered circadian rhythms and synchronization to light.     

Germling fusion via conidial anastomosis tubes in the grey mould Botrytis cinerea requires NADPH oxidase activity

In many filamentous ascomycete species, the early steps of colony development include fusion between germinating vegetative spores (conidial germlings). Often these fusion events are mediated by specialized hyphal structures, so-called conidial anastomosis tubes (CATs). Here, we show that germling fusion in the grey mould Botrytis cinerea is mediated by hyphal structures possessing the typical features of CATs. Formation of these structures is delayed when spores are germinating on complex media compared to growth on poor substrates. Fusion frequency is also influenced by the growth conditions of the precultures from which spores were obtained. During germination on hydrophobic plant surfaces, which induce pathogenic development, CAT formation is significantly suppressed. Screening of existing B. cinerea gene knockout mutants identified strains lacking the NADPH oxidase BcNoxA or the potential Nox regulator BcNoxR as fusion deficient, suggesting a potential role of reactive oxygen species (ROS) signalling in CAT formation and fusion.     

大隐静脉顺行序贯式吻合技术在冠心病患者中的应用

目的:探讨大隐静脉(SVG)顺行序贯式吻合技术在冠心病患者中的应用价值。方法:收集我院2011年1月至2014年6月收治的78例冠心病患者,回顾性分析患者非体外循环下行SVG顺行序贯式冠状动脉旁路移植术患者的临床资料,术后随访1~3.5年,平均(2.1±1.5)年,密切观察患者治疗效果以及相应的并发症的发生情况。结果:SVG双支桥48例,三支桥20例,四支桥10例,吻合口共196个。术后测定近段血流流速(37.14±11.78)m L/min,搏动指数(PI)值(3.00±1.25)。术后出现2例低心排血量综合征,2例迟发性心脏压塞,除1例因序贯出现多脏器功能衰竭而死亡外,其余均痊愈。术后复查,SVG桥的通畅率为100%。结论:SVG顺行序贯吻合能尽快恢复心脏供血,术后通畅率高,在医生严格掌握手术技巧的前提下,可安全用于冠心病的治疗。     

Effects of triazolopyrimidine on lipid peroxidation and nitric oxide levels in the corticosteroid-impaired healing of rat tracheal anastomoses

Corticosteroids are used to reduce the oedema and prevent scar tissue formation of the upper airways by their ability to inhibit influx of inflammatory cells, limit capillary permeability and block collagen synthesis in the early stages of wound healing. Triazolopyrimidine (Trapidil) is an antiplatelet agent that acts in part as a phosphodiesterase inhibitor and as a competitive inhibitor of the platelet-derived growth factor (PDGF) receptor. Trapidil, with its vasodilator and NO releasing effect may have some potential to diminish the tissue injury. This study was carried out to evaluate the effects of trapidil (triazolopyrimidine) on lipid peroxidation and nitric oxide in the corticosteroid-impaired healing of tracheal anastomoses. Thirty-four adult Wistar rats were divided into five groups. The animals underwent tracheal transection and primary anastomoses. The groups were assigned as follows: group I, control, (GI, n = 6); group II, sham, (GII, n = 6); group III, dexamethasone, 0.1 mg kg(-1) twice daily intramuscularly, (GIII, n = 8); group IV, trapidil, 6 mg kg(-1) twice daily intraperitoneally (GIV, n = 7); group V, dexamethasone, 0.1 mg kg(-1) plus trapidil, 6 mg kg(-1) twice daily (GV, n = 7), for 1 week. After 1 week, anastomotic healing was assessed by measurement of bursting pressure, evaluation of histopathology, measurement of MDA and nitrite/nitrate levels. In GIII, GIV and GV bursting pressures resulted in significantly reduced anastomotic strength compared to the controls (p < 0.001 for all groups). The difference between bursting pressures of GIII and GIV was not found to be statistically significant (p = 0.966). In regard to fibroblast proliferation and collagen content, a significant difference was found between GIII and GI (p < 0.01), A significant difference was also found when GIV and GV were compared to GIII (p < 0.01). MDA and nitrite/nitrate levels were found to be higher in GIII when compared to all other groups. MDA levels of GIV and GV rats were found to be lower than GIII (p < 0.001, for both groups). The nitrite/nitrate levels of GIV and GV rats were found to be lower than GIII (p < 0.05), and higher than GI (p < 0.001). Trapidil may be useful for its preventive effects on lipid peroxidation and possible increases in NO in cases with corticosteroid-impaired healing of trachea anastomoses.     

Regional Differences in the Capacity for Ammonia Removal by Brain Following Portocaval Anastomosis

Portocaval anastomosis (PCA) in the rat leads, within 4 weeks, to severe liver atrophy, sustained hyperammonemia, and increased brain ammonia. Because brain is not equipped with an effective urea cycle, removal of ammonia involves glutamine synthesis and PCA results in significantly increased brain glutamine. Glutamine synthetase activities, however, are decreased by 15% in cerebral cortex and are unchanged in brainstem of shunted rats. Administration of ammonium acetate to rats following PCA results in severe encephalopathy (loss of righting reflex and, ultimately, coma). Glutamine concentrations in brainstem of comatose rats are increased a further two-fold, whereas those of cerebral cortex are unchanged. Consequently, ammonia levels in cerebral cortex reach disproportionately high levels (of the order of 5 mM). These findings suggest a limitation in the capacity of cerebral cortex to remove additional blood-borne ammonia by glutamine formation following PCA. Such mechanisms may explain the hypersensitivity of rats with PCA and of patients with portal-systemic shunting to small increases of blood ammonia. Disproportionately high levels of brain ammonia in certain regions, such as cerebral cortex, may then result in alterations of inhibitory neurotransmission and, ultimately, loss of cellular (astrocytic) integrity.     

An ultrastructural study of cell-cell interactions in capture organs of the nematophagous fungus Arthrobotrys oligospora

Abstract A detailed ultrastructural analysis was made of interactions between individual cells within the same adhesive network (trap) of the nematophagous fungus Arthrobotrys oligospora . These interactions were confined to traps which had captured nematodes, and occurred concurrently with the fungus-nematode interactions. The process was initiated by the anchoring of 2 cells of different loops constituting the trap network, by means of the adhesive coating of these cells. Subsequently, penetration tubes were formed. As in nematode-fungus interactions, the walls of these tubes arose from underneath the original trap cell walls. Two response were observed: either only one of the anchored cells formed a penetration tube, which penetrated the opposite cell and subsequently digested its contents; or both cells formed penetration tubes simultaneously, which were directed against each other. In the latter case, no penetration of other cells was observed, and elongated tubes were occasionally formed. The above mechanism differed from 2 other modes of interaction also observed, namely fusion of intact cells (anastomosis) and development of new hyphae inside dead hyphal cells. In the latter case the newly formed cells developed from the cross-wall of the neighbouring intact cell.     

Influence of peripheral targets on the expression of calcitonin gene-related peptide immunoreactivity in rat cranial motoneurones

Calcitonin gene-related peptide-like immunoreactivity (CGRP-ir) is displayed by motoneurons that innervate striated muscle but is absent from preganglionic parasympathetic motoneurons. One hypothesis to explain this is that CGRP gene expression in motoneurons is, in part, dependent on influences from the innervated organ. To test this hypothesis, we cross-anastomosed the right hypoglossal and cervical vagal nerves of rats so that the vagal motoneurons grew to innervate the musculature of the tongue. Following a recovery period of 17 to 52 weeks, the distribution of CGRP-ir in the dorsal motor vagal nucleus was determined in both cross-anastomosed animals and self-anastomosed control animals. Successful reinnervation of the tongue musculature by vagal motoneurons was demonstrated by showing that electrical stimulation of the central vagus/peripheral hypoglossal nerve produced a twitch of the tongue muscles. Motoneurones of the dorsal motor vagal nucleus, which now innervated the tongue were found to express CGRP-ir, which was evident from the double labeling of neurons with both horseradish peroxidase and CGRP-ir. Motoneurones of the dorsal motor vagal nucleus contralateral to the cross-anastomosis remained CGRP negative. Similarly, motoneurons of the dorsal motor vagal nucleus in control animals where the vagus nerve was self-anastomosed remained CGRP negative, showing that an induction of CGRP expression is not a result of nerve section itself. We suggest that a signal from the striated muscle transported retrogradely via the motor axon regulates expression of CGRP-ir in motoneurons. © 1995 John Wiley & Sons, Inc.     

Stem cell therapy applied for digestive anastomosis: Current state and future perspectives

BACKGROUND Digestive tract resections are usually followed by an anastomosis.Anastomotic leakage,normally due to failed healing,is the most feared complication in digestive surgery because it is associated with high morbidity and mortality.Despite technical and technological advances and focused research,its rates have remained almost unchanged the last decades.In the last two decades,stem cells(SCs)have been shown to enhance healing in animal and human studies;hence,SCs have emerged since 2008 as an alternative to improve anastomoses outcomes.AIM To summarise the published knowledge of SC utilisation as a preventative tool for hollow digestive viscera anastomotic or suture leaks.METHODS PubMed,Science Direct,Scopus and Cochrane searches were performed using the key words“anastomosis”,“colorectal/colonic anastomoses”,“anastomotic leak”,“stem cells”,“progenitor cells”,“cellular therapy”and“cell therapy”in order to identify relevant articles published in English and Spanish during the years of 2000 to 2021.Studies employing SCs,performing digestive anastomoses in hollow viscera or digestive perforation sutures and monitoring healing were finally included.Reference lists from the selected articles were reviewed to identify additional pertinent articles.METHODS Given the great variability in the study designs,anastomotic models,interventions(SCs,doses and vehicles)and outcome measures,performing a reliable meta-analysis was considered impossible,so we present the studies,their results and limitations.RESULTS Eighteen preclinical studies and three review papers were identified;no clinical studies have been published and there are no registered clinical trials.Experimental studies,mainly in rat and porcine models and occasionally in very adverse conditions such as ischaemia or colitis,have been demonstrated SCs as safe and have shown some encouraging morphological,functional and even clinical results.Mesenchymal SCs are mostly employed,and delivery routes are mainly local injections and cell sheets followed by biosutures(sutures coated by SCs)or purely topical.As potential weaknesses,animal models need to be improved to make them more comparable and equivalent to clinical practice,and the SC isolation processes need to be standardised.There is notable heterogeneity in the studies,making them difficult to compare.Further investigations are needed to establish the indications,the administration system,potential adjuvants,the final efficacy and to confirm safety and exclude definitively oncological concerns.CONCLUSION The future role of SC therapy to induce healing processes in digestive anastomoses/sutures still needs to be determined and seems to be currently far from clinical use.