健脾消癌方通过PI3K/Akt信号通路抑制结肠癌血管生成的研究＊

目的 观察结肠癌HCT116细胞健脾消癌方的条件培养液对HUVEC细胞管腔形成的影响，从PI3K/Akt生物轴调控角度探讨其作用机制。方法 培养HCT116细胞，细胞设3组：对照组，健脾消癌方组（加入15%健脾消癌方含药血清）及人参皂苷Rg3组；制备HCT116细胞健脾消癌方条件培养液（分组及制备方法见实验方法），用条件培养液干预HUVEC（脐静脉内皮细胞，Human Umbilical Vein Endothelial Cells），Matrigel基质胶法检测HCT116细胞健脾消癌方条件培养液对HUVEC小管形成的影响。随后采用蛋白免疫印迹法（Western blot）检测各组HCT116细胞磷脂酰肌醇3-激酶（PI3K）、蛋白激酶B（Akt）、p-Akt、VEGF（血管内皮生长因子，Vascular endothelial growth factor）蛋白表达。最后在结肠癌HCT116荷瘤小鼠中验证健脾消癌方对肿瘤生长速度的影响，并经瘤组织VEGF蛋白表达、CD31免疫组化染色检测肿瘤内血管生成情况。结果 模型组HUVEC细胞管腔形成较空白血清组显著增加（P<0.05）；健脾消癌方组及人参皂苷Rg3组较模型组HUVEC细胞管腔形成显著减少（P<0.01）。p-Akt和VEGF蛋白表达水平模型组高于空白血清组（P<0.05），健脾消癌方组及人参皂苷Rg3组显著低于模型组（P<0.01）；PI3K、Akt蛋白表达量组间差异无统计学意义。与对照组比较，模型组荷瘤小鼠肿瘤体积显著性增大，瘤组织内VEGF表达、CD31阳性面积显著性增加，差异有统计学意义（P<0.05）；与模型组比较，健脾消癌方组及人参皂苷Rg3组荷瘤小鼠肿瘤体积显著减小，瘤组织内VEGF表达、CD31阳性面积降低，差异有统计学意义（P<0.05）。结论 健脾消癌方可抑制肿瘤的血管生成和生长，其作用机制可能与PI3K/Akt生物轴调控VEGF表达有关。     

Do social support and community engagement act as mechanisms in the association between neighbourhood income inequality and the mental health of mothers in Calgary,Canada? A mediation analysis

PurposeAccording to the social determinants of health framework, income inequality is a potential risk factor for adverse mental health. However, few studies have explored the mechanisms suspected to mediate this relationship. The current study addresses this gap through a mediation analysis to determine if social support and community engagement act as mediators linking neighbourhood income inequality to maternal anxiety and depressive symptoms within a cohort of new mothers living in the City of Calgary, Canada.MethodsData collected at three years postpartum from mothers belonging to the All Our Families (AOF) cohort were used in the current study. Maternal data were collected between 2012 and 2015 and linked to neighbourhood socioeconomic data from the 2006 Canadian Census. Income inequality was measured using Gini coefficients derived from 2006 after-tax census data. Generalized structural equation models were used to quantify the associations between income inequality and mental health symptoms, and to assess the potential direct and indirect mediating effects of maternal social support and community engagement.ResultsIncome inequality was not significantly associated with higher depressive symptoms (β = 0.32, 95%CI = −0.067, 0.70), anxiety symptoms (β = 0.11, 95%CI = −0.39, 0.60), or lower social support. Income inequality was not associated with community engagement. For the depression models, higher social support was significantly associated with lower depressive symptoms (β = −0.13, 95%CI = −0.15, −0.097), while community engagement was not significantly associated with depressive symptoms (β = 0.059, 95%CI = −0.15, 0.27). Similarly, for the anxiety models, lower anxiety symptoms were significantly associated with higher levels of social support (β = −0.17, 95%CI = −0.20, −0.13) but not with higher levels of community engagement (β = 0.14, 95%CI = −0.14, 0.41).ConclusionThe current study did not find clear evidence for social support or community engagement mediating the relationship between neighbourhood income inequality and maternal mental health. Future investigations should employ a broader longitudinal approach to capture changes in income inequality, potential mediators, and mental health symptomatology over time.     

补充与替代疗法治疗肠易激综合征的研究进展

肠易激综合征是临床常见的功能性胃肠病之一。由于多数患者的症状经过一线药物治疗后仍不能得到较好改善，许多患者为获得更好的治疗效果，转向选择补充与替代疗法进行治疗。然而，由于研究质量和数量的限制，大部分治疗肠易激综合征的补充与替代疗法并未被相关共识和指南所推荐。本文从补充与替代疗法的分类入手，从天然产品、身心治疗、传统医药3个方面就目前国内外常用的补充与替代疗法治疗肠易激综合征的研究进行概述，以期为临床工作者和患者更好地了解和应用提供帮助。     

女性致密性骨炎血清骨转换生化标志物水平变化研究

背景 致密性骨炎（OCI）和其他疾病有时难以鉴别，探讨血清骨转换生化标志物可为OCI的鉴别诊断提供依据。 目的 探索女性OCI患者的血清骨转换生化标志物的水平变化及临床意义。 方法 回顾性选取2013年6月至2022年2月在北京积水潭医院门诊及住院诊断为OCI的61例女性患者作为观察组，年龄15~50岁，平均（33.8±6.6）岁，病程2周~15年。选择同期61例女性体检健康者作为对照组，年龄15~48岁，平均（35.6±7.6）岁。比较两组一般临床资料和血清骨转换生化标志物水平，并对血清骨转换生化标志物与病情相关指标进行相关性分析。 结果 观察组血清白蛋白（45.4±2.9）g/L低于对照组（46.5±2.8）g/L（t=2.190，P<0.05）。血清骨转换生化标志物比较结果显示，观察组血清1型胶原羧基末端肽β特殊序列（β-CTX）〔0.28（0.23，0.37）μg/L〕、N-端骨钙素（OC）〔13.1（11.2，16.2）μg/L〕、25-羟维生素D3〔25-（OH）VD3〕〔（14.1±5.1）μg/L〕低于对照组〔0.36（0.29，0.48）μg/L，15.6（13.7，17.3）μg/L，（17.5±6.6）μg/L〕（Z=-2.983、-3.255，t=3.081，P<0.05）。长病程亚组OC水平〔14.6（12.4，18.5）μg/L〕高于短病程亚组〔11.7（10.2，14.0）μg/L〕（Z=-2.407，P<0.05）。多孕亚组β-CTX〔0.25（0.22，0.32）μg/L〕、OC水平〔12.2（10.3，15.0）μg/L〕低于非多孕亚组〔0.33（0.26，0.44）μg/L、13.4（12.0，18.8）μg/L〕（Z=-2.486、-1.897，P<0.05）。相关性分析显示，观察组血清1型前胶原氨基端延长肽（tP1NP）与妊娠次数、生产次数均呈负相关（rs=-0.276、-0.298，P<0.05），OC与体质指数（BMI）、视觉模拟评分法（VAS）评分、妊娠次数均呈负相关（rs=-0.284、-0.374、-0.360，P<0.05），25-（OH）VD3水平与BMI呈正相关（rs=0.275，P<0.05）。 结论 女性OCI患者血清OC、β-CTX水平明显降低，可为鉴别其他疾病提供依据；血清OC水平可以反映OCI患者的严重程度，同时OC水平与患者妊娠次数相关；tP1NP与妊娠次数、生产次数相关。     

Diagnostic pitfalls in needle core biopsy of the breast

Breast core biopsies are a standard component of the triple approach that includes clinical examination, imaging and tissue sampling. Conventional cores, diagnostic vacuum assisted biopsy and vacuum assisted excisions are established methods for sampling and managing breast lesions. It is important to be aware of the potential pitfalls in the technical handling and interpretation of the limited core biopsy samples. Here, we present a clinically oriented, well illustrated overview of the common diagnostic pitfalls based on the author's diagnostic and second opinion practice, emphasize the value of clinicopathological correlation and provide histological tips and clues with useful immunohistochemistry to aid the reporting pathologists in their daily interpretation of breast core biopsies.     

Le traumatisme psychique constitue une blessure du langage par atteinte des réseaux de significations

ObjectivesTrauma appears within the discourse of mentally injured people, materializing what we have recently defined as “post traumatic psycholinguistic syndrome” (SPLIT). Translating unspeakability, revival, and dissociation, this clinical entity associates three significant disturbances : traumatic anomia (missing words, reduction of the elocutionary flow, deictic gestures, etc.); linguistic repetitions (of words and phrases, verbal intrusions, echophrasias, etc.); and phrasal and discursive disorganization (incomplete sentences, tense discordance, dysfluence, lack of logical connectors, etc.). What are the causes of these semiological and psycholinguistic expressions? What are their psychological and/or neuropsychological processes? It is time to come up with a new concept intended to go beyond the previous models in order to better identify people suffering from post-traumatic mental disorders, to better organize and evaluate psychotherapeutic care, and also to help practitioners collaborate more effectively on these first two goals. But how to evoke, affirm, or speak out about the consequences of unspeakability? Nothing is more apparently contradictory than wanting to define the language void. How to account for the fractures of psychic trauma in discourse? Nothing is more uncertain than to try to organize the upheavals, the disorders caused by dissociation in language. Finally, how to specify the reiteration of the trauma using words and sentences without this modeling being dissociative or repetitive? Today, thanks to a psycholinguistic reading, essential dimensions of post-traumatic suffering, hitherto hidden, can be clarified. Why exactly does an event cause trauma in the life of a subject at a given moment in her/his existence? Why is a latency phase structured between the traumatic event and the return of reviviscences under the influence of a re-triggering factor? How to differentiate the notion of dissociation as a normal phenomenon from the so-called traumatic dissociation? How to explain the multiple clinical forms of post-traumatic psychological disorders?MethodsFrom Pierre's clinical history, we chronologically detail the structuring and the consequences of the signified reflection that are constitutive of the psychic trauma: the psycholinguistic tools here help to formulate a new etiopathogenic conception of trauma and its psychological consequences. Then, thanks to Jean's testimony, taking up the retrospective meaning of the clinical analysis from chronic repetition syndrome, we discover the phases of tension regarding signified knowledge, up to the network prior to the traumatic confrontation. Finally, illustrated by Karima's disorder, beyond depersonalization, we explain that the analysis of the disturbances of a singular signified network, and also of an attack on its familial and societal bases, testifies to individual and collective subjectivities.ResultsComing from the real world, and therefore also from the body, the stimuli made up of signals picked up by our senses combine to compose an event that can be objectified by its temporal, spatial, biological, and physico-chemical coordinates. These elements combine into a unit, which is then interpreted by the mind, which attributes meaning to this event, which has become subjective reality. But when the subject is not sufficiently prepared to be confronted with this meaning that appears to be in extreme contradiction with her/his previous cardinal networks of significations, it makes “too much sense:” this irreconcilable hyper-signified (that we call the traumatic signified) results in post-traumatic dissociation. In other words, it is an impossibility of concordance of a signified with certain systems of prior significations that constitutes the pathogenesis of the trauma; and a situation runs a greater risk of being traumatic when it contradicts, or, moreso, endangers some or all of the subject's cardinal meanings. This unbearable signified reflexively blocks the capacities of significations immediately pre- and post-trauma, then dissociates the psychic functions to varying degrees and intensities. The traumatic signified, rejected, becomes unattainable: the stimuli that led to its formation find themselves confined to the state of reviviscences, each replication of which attempts to cross the barrier of inconceivability. Limiting sensory compounds to their raw states without the possibility of representational integration, associative pathways remain blocked. The signifier is referred to a hypo-signifier confined to the infra-linguistic by its confusion with the referent, the “objective and material” components of the traumatic event. Dissociation is therefore only a symptomatic reaction, secondary to the trauma, which it reinforces once again by limiting any possibility of representing the trauma. This dissociation does not involve forgetting the traumatic signified but “protects” the adjacent networks of meanings from it as much as it “keeps” this hypersignified intact, therefore ultimately “protecting” it as well. The traumatic signified persists somewhere, and even ends up being found everywhere: when the networks of meanings turn out to be globally disturbed, the tightest links remain those of the traumatic hypersignified that ultimately governs all the networks of meanings.DiscussionOur insufficient knowledge prevents us from precisely qualifying the architecture of the signified idiosyncratic networks and their evolutionary capacities; we cannot predict, beforehand, the reaction of an individual confronted with a potentially psychotraumatic situation. For most clinical situations, we affirm that the psychological trauma occurs in a psychically healthy subject, that is, not suffering from any psychiatric illness or any obvious psychopathological conflict. Psychotherapy will make it possible to discover the signified, sometimes ancient, origins of a trauma occurring in a singular subject. How was this subjectivity constructed? Beyond individual subjectivity, the intensity of certain confrontations such as serious attacks or macrosocial catastrophes such as genocide, would seem to lead to psychological wounds in any individual, even at the scale of a population. While, throughout existence, each subject produces a system of significations in connection with a unique psychic construction, the latter persists – resulting from, and often remaining overseen by, the community essence of a base of signifying networks, which we call “societal subjectivity.” Here, the psychological trauma can correspond to an individual and “common” injury as a failure of a sharing, or of ancestral beliefs anchored in the collective memory, defining the culture. By the collapse of acquired certainties, the cognitive patterns transmitted by education, language, and everything that establishes one's belonging to a society, trauma shakes the networks of individual and group meanings. Horror has a higher traumatogenic risk, because it defeats the fundamentals of humankind, the foundations of a signified network common to a culture, or even to all cultures, to the human condition. This is the case with murder, rape, torture, wars, genocides. Testifying to an instinct for survival stemming from the biological foundations of every living being, the impossibility of “living death” appears to be anchored in our networks of meanings and is manifested by indescribability, traumatic as such: being deserted by the language collides with the condition of speaking. And yet, it remains possible to say something about it... As a path of progressive desocialization, the occasional loss of the community of language, followed by its lasting traumatic ravages, can be appeased by the reestablishment of a speech link, either within the mind of the subject alone, or promoted by the exchange with others, in a psychotherapeutic setting, for example.ConclusionWhere theoretical discourses have sometimes proved divisive, going beyond the symptoms of indescribability and dissociation, psychodynamic practice today offers to unite. Thanks to psycholinguistic listening, phenomena that have never been explained take on meaning: the singularity of traumatic perception, the chronology of disorders including the latency phase, factors that trigger reviviscences, and the diversity of chronic clinical forms. All these post-traumatic symptoms are consequential to a linguistic wound, a difficulty in accessing meaning, the undermining of two dimensions characterizing and constructing the human being. As much as it integrates extralinguistic determinants, if the traumatic signified is undoubtedly not only speech, language appears the optimal way to identify it as such, while in the same movement appeasing it. The traumatic hypersignified is discovered through clinical analysis and psychotherapy, through deferred action, through the attribution of meaning, through the retrospective reconstruction of an unstable “real,” through a changing narration eternally distancing itself from reviviscences. But what precisely are the mechanisms of effective therapies ? What are the intersubjective links called for in the discussion between patient and practitioner? Could the operations that we call “psychotherapy” be made up of mobilizations of the networks of meanings by speech acts?     

Higher Preimplantation Opioid Doses Associated With Long‐Term Spinal Cord Stimulation Failure in 211 Patients With Failed Back Surgery Syndrome

ObjectiveSpinal cord stimulation (SCS) is an effective treatment in failed back surgery syndrome (FBSS). We studied the effect of preimplantation opioid use on SCS outcome and the effect of SCS on opioid use during a two-year follow-up period.Materials and methodsThe study cohort included 211 consecutive FBSS patients who underwent an SCS trial from January 1997 to March 2014. Participants were divided into groups, which were as follows: 1) SCS trial only (n = 47), 2) successful SCS (implanted and in use throughout the two-year follow-up period, n = 131), and 3) unsuccessful SCS (implanted but later explanted or revised due to inadequate pain relief, n = 29). Patients who underwent explantation for other reasons (n = 4) were excluded. Opioid purchase data from January 1995 to March 2016 were retrieved from national registries.ResultsHigher preimplantation opioid doses associated with unsuccessful SCS (ROC: AUC = 0.66, p = 0.009), with 35 morphine milligram equivalents (MME)/day as the optimal cutoff value. All opioids were discontinued in 23% of patients with successful SCS, but in none of the patients with unsuccessful SCS (p = 0.004). Strong opioids were discontinued in 39% of patients with successful SCS, but in none of the patients with unsuccessful SCS (p = 0.04). Mean opioid dose escalated from 18 ± 4 MME/day to 36 ± 6 MME/day with successful SCS and from 22 ± 8 MME/day to 82 ± 21 MME/day with unsuccessful SCS (p < 0.001).ConclusionsHigher preimplantation opioid doses were associated with SCS failure, suggesting the need for opioid tapering before implantation. With continuous SCS therapy and no explantation or revision due to inadequate pain relief, 39% of FBSS patients discontinued strong opioids, and 23% discontinued all opioids. This indicates that SCS should be considered before detrimental dose escalation.     

Association of vitamin D levels and risk of latent tuberculosis in the hemodialysis population

BackgroundVitamin D is essential in the host defense against tuberculosis (TB). Suboptimal vitamin D status is common in the hemodialysis population. Hemodialysis patients have an increased risk compared to the general population latent tuberculosis infection (LTBI). However, the association between vitamin D deficiency and LTBI in this population remains unclear.Materials and methodsWe conducted a cross-sectional study between March and May 2017. Interferon-gamma release assay (IGRA) through QuantiFERON-TB Gold In-Tube was used to assess LTBI. Plasma 25-hydroxycholecalciferol (25-OHD) levels were measured by Elecsys Vitamin D Total assay. Suboptimal vitamin D levels included vitamin D insufficiency 20–29 ng/mg and vitamin D deficiency <20 ng/mL. Predictors for LTBI were analyzed.ResultsA total of 287 participants were enrolled. The suboptimal vitamin D level was 31.4% (90/287), which including the vitamin D deficiency was 13.9% (40/287). A total of 49.1% (141/287) people received nutritional vitamin D supplementation. The prevalence of IGRA positivity in this study was 25.1% (72/287). There was no significant difference in vitamin D concentrations or the proportion of vitamin D supplementation among the IGRA-positive and IGRA-negative groups (p = 0.789 and 0.496, respectively). In multivariate analysis, age >65 years old (odds ratio (OR), 1.89; 95% CI, 1.08–3.31; p = 0.026) and TB history (OR, 3.51; 95% CI, 1.38–8.91; p = 0.008) were independent predictors of IGRA positivity.ConclusionThis is the first study to report that vitamin D deficiency was not associated with IGRA positivity in a hemodialysis population. Aging and TB history were both independent predictors for LTBI.