Analysis on internal mechanism of zedoary turmeric in treatment of liver cancer based on pharmacodynamic substances and pharmacodynamic groups

Zedoary tumeric (Curcumae Rhizoma, Ezhu in Chinese) has a long history of application and has great potential in the treatment of liver cancer. The anti liver cancer effect of zedoary tumeric depends on the combined action of multiple pharmacodynamic substances. In order to clarify the specific mechanism of zedoary tumeric against liver cancer, this paper first analyzes the mechanism of its single pharmacodynamic substance against liver cancer, and then verifies the joint anti liver cancer mechanism of its "pharmacodynamic group". By searching the research on the anti hepatoma effect of active components of zedoary tumeric in recent years, we found that pharmacodynamic substances, including curcumol, zedoarondiol, curcumenol, curzerenone, curdione, curcumin, germacrone, β-elemene, can act on multi-target and multi-channel to play an anti hepatoma role. For example, curcumin can regulate miR, GLO1, CD133, VEGF, YAP, LIN28B, GPR81, HCAR-1, P53 and PI3K/Akt/mTOR, HSP70/TLR4 and NF-κB. Wnt/TGF/EMT, Nrf2/Keap1, JAK/STAT and other pathways play an anti hepatoma role. Network pharmacological analysis showed that the core targets of the "pharmacodynamic group" for anti-life cancer are AKT1, EGFR, MAPK8, etc, and the core pathways are neuroactive live receiver interaction, nitrogen metabolism, HIF-1 signaling pathway, etc. At the same time, by comparing and analyzing the relationship between the specific mechanisms of pharmacodynamic substance and "pharmacodynamic group", it is found that they have great reference significance in target, pathway, biological function, determination of core pharmacodynamic components, formation of core target protein interaction, in-depth research of single pharmacodynamic substance, increasing curative effect and so on. By analyzing the internal mechanism of zedoary tumeric pharmacodynamic substance and "pharmacodynamic group" in the treatment of liver cancer, this paper intends to provide some ideas and references for the deeper pharmacological research of zedoary tumeric and the relationship between pharmacodynamic substance and "pharmacodynamic group".     

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.     

COVID-19 Gender Disparities and Mitigation Recommendations: A Narrative Review

The coronavirus disease 2019 (COVID-19) pandemic has rapidly created widespread impacts on global health and the economy. Data suggest that women are less susceptible to severe illness. However, sex-disaggregated data are incomplete, leaving room for misinterpretation, and focusing only on biologic sex underestimates the gendered impact of the pandemic on women. This narrative review summarizes what is known about gender disparities during the COVID-19 pandemic and the economic, domestic, and health burdens along with overlapping vulnerabilities related to the pandemic. In addition, this review outlines recommended strategies that advocacy groups, community leaders, and policymakers should implement to mitigate the widening gender disparities related to COVID-19.     

Emergency Care EMTALA Alterations During the COVID-19 Pandemic in the United States

The coronavirus 2019 pandemic has affected almost every aspect of health care delivery in the United States, and the emergency medicine system has been hit particularly hard while dealing with this public health crisis. In an unprecedented time in our history, medical systems and clinicians have been asked to be creative, flexible, and innovative, all while continuing to uphold the important standards in the US health care system. To continue providing quality services to patients during this extraordinary time, care providers, organizations, administrators, and insurers have needed to alter longstanding models and procedures to respond to the dynamics of a pandemic. The Emergency Medicine Treatment and Active Labor Act of 1986, or EMTALA, is 1 example of where these alterations have allowed health care facilities and clinicians to continue their work of caring for patients while protecting both the patients and the clinicians themselves from infectious exposures at the same time.