内源性硫化氢和基于中医气血理论的血瘀证之间的关系

“Qi” and “blood” are two essential concepts in Chinese medicine (CM). As qi is intangible, the concept of qi is still controversial between CM and Western medicine. However, the endogenous hydrogen sulfide (H₂S) and other gaseous signaling molecules provides a new approach for understanding the essence of qi in CM. Blood stasis syndrome is a common syndrome in CM. According to the CM theory, the incidence of blood stasis syndrome is closely correlated to the reckless movement of qi, as qi and blood are inseparable in regulating physiological functions. In recent years, more and more evidences suggest a close correlation between blood stasis syndrome and microcirculation dysfunction. In this paper, we discuss the relationship between endogenous H₂S and blood stasis syndrome based on qi-blood theory of CM. We found that endogenous H₂S maybe a material basis in concept of qi in CM, while dysfunctional microcirculation is the pathological basis of the blood stasis syndrome. As qi is closely associated with incidence and progression of blood stasis syndrome, endogenous H₂S may play an important role in preventing and treating the blood stasis syndrome by improving the function of microcirculation.     

Implication of Human Endogenous Retrovirus Envelope Proteins in Placental Functions

Human endogenous retroviruses (ERVs) represent 8% of the total human genome. Although the majority of these ancient proviral sequences have only retained non-coding long terminal repeats (LTRs), a number of “endogenized” retroviral genes encode functional proteins. Previous studies have underlined the implication of these ERV-derived proteins in the development and the function of the placenta. In this review, we summarize recent findings showing that two ERV genes, termed Syncytin-1 and Syncytin-2, which encode former envelope (Env) proteins, trigger fusion events between villous cytotrophoblasts and the peripheral multinucleated syncytiotrophoblast layer. Such fusion events maintain the stability of this latter cell structure, which plays an important role in fetal development by the active secretion of various soluble factors, gas exchange and regulation of fetomaternal immunotolerance. We also highlight new studies showing that these ERV proteins, in addition to their localization at the cell surface of cytotrophoblasts, are also incorporated on the surface of various extracellular microvesicles, including exosomes. Such exosome-associated proteins could be involved in the various functions attributed to these vesicles and could provide a form of tropism. Additionally, through their immunosuppressive domains, these ERV proteins could also contribute to fetomaternal immunotolerance in a local and more distal manner. These various aspects of the implication of Syncytin-1 and -2 in placental function are also addressed in the context of the placenta-related disorder, preeclampsia.     

Towards human ex vivo organ perfusion models to elucidate drug pharmacokinetics in health and disease

Abstract

To predict the absorption, distribution, metabolism and excretion (ADME) profile of candidate drugs a variety of preclinical models can be applied. The ADME and toxicological behavior of newly developed drugs are often investigated prior to assessment in humans, which is associated with long time-lines and high costs. Therefore, good predictions of ADME profiles earlier in the drug development process are very valuable. Good prediction of intestinal absorption and renal and biliary excretion remain especially difficult, as there is an interplay of active transport and metabolism involved. To study these processes, including enterohepatic circulation, ex vivo tissue models are highly relevant and can be regarded as the bridge between in vitro and in vivo models. In this review the current in vitro, in vivo and in more detail ex vivo models for studying pharmacokinetics in health and disease are discussed. Additionally, we propose novel models, i.e., perfused whole-organs, which we envision will generate valuable pharmacokinetic information in the future due to improved translation to the in vivo situation. These machine-perfused organ models will be particularly interesting in combination with biomarkers for assessing the functionality of transporter and CYP450 proteins.     

Reappraisal of Dementia Praecox: Focus on Clinical Psychopathology

Summary: One century of investigation in schizophrenia is still not enough to elucidate all the complex issues related to the essential symptomatology, clinical boundaries, aetiology, pathogenesis, outcome, treatment and prevention. Despite the extraordinary progress in the neuroscience field, no definitive data is available for schizophrenia. On the other hand, after the successful activity of the psychopharmacological era, the clinical psychopathological investigations were reduced and almost replaced by the mechanistic operational diagnosis. This has caused an impoverishment in psychiatry. Tracing some historical aspects of schizophrenia since the kraepelinian Dementia Praecox, this article intends to demonstrate the failure of the current model of diagnosis and current limitation of neuroscience. It advocates the reinforcement of Clinical Psychopathology as the foundation for correct and appropriate first steps in the investigation of schizophrenia. The splitting disease is still a challenge to biological psychiatry.     

CYP2D6 variation,behaviour and psychopathology: implications for pharmacogenomics-guided clinical trials

Individual and population differences in polymorphic cytochrome P450 enzyme function have been known for decades. The biological significance of these differences has now been deciphered with regard to drug metabolism, action and toxicity as well as disposition of endogenous substrates, including neuroactive compounds. While the cytochrome P450 enzymes occur abundantly in the liver, they are expressed in most tissues of the body, albeit in varying amounts, including the brain. The latter location of cytochrome P450s is highly pertinent for susceptibility to neuropsychiatric diseases, not to mention local drug metabolism at the site of psychotropic drug action in the brain. In the current era of personality medicine with companion theranostics (i.e. the fusion of therapeutics with diagnostics), this article underscores that such versatile biological roles of cytochrome P450s offer multiple points of entry for personalized medicine and rational therapeutics. We focus our discussion on CYP2D6, one of the most intensively researched drug and endogenous compound metabolism pathways, with a view to relevance for, and optimization of, pharmacogenomic-guided clinical trials. Working on the premise that CYP2D6 is related to human behaviour and certain personality traits such as serotonin and dopamine system function, we further suggest that the motivation of healthy volunteers to participate in clinical trials may in part be influenced by an under-or over-representation of certain CYP2D6 metabolic groups.     

Endogenous lipoid pneumonia presenting as solitary pulmonary nodule: a case report

A 63-year-old woman complained of hemoptysis was admitted to our hospital. Chest computed tomography (CT) showed a solitary pulmonary nodule (SPN) arising from the lower lobe of the right lung which was considered as lung malignancy. The patient underwent video-assisted thoracoscopic surgery (VATS) of pulmonary wedge resection to remove the nodule. Diagnosis of lipoid pneumonia was established by multiple lipid-laden macrophages found in surgical specimen. As there was no history of inhalation or aspiration of lipid containing substances, she was diagnosed as endogenous lipoid pneumonia. The patient discharged from our hospital after surgery and with no recurrence in 9 months period.     

苏叶地黄汤治疗慢性肾衰竭临床观察

目的：观察苏叶地黄汤治疗早中期慢性肾衰竭（ chronic renal fcilure,CRF）的临床疗效。方法：将符合标准的68例CRF患者在基础治疗同时予以自拟苏叶地黄汤口服,观察治疗前后患者尿素氮、肌酐、内生肌酐清除率、血红蛋白、24 h尿蛋白定量变化情况。结果：68例患者中显效43例,稳定14例,无效11例,有效率为83.80%。治疗后尿素氮、肌酐、内生肌酐清除率、24 h尿蛋白定量等指标均有明显改善,与治疗前比较,差异有统计学意义（ P<0.05）。结论：苏叶地黄汤能有效改善早中期CRF患者肾功能水平。     

Chronic endogenous fungal endophthalmitis: diagnostic and treatment challenges: A case report

Rationale:Endogenous fungal endophthalmitis (EFE) is a sight-threatening complication of systemic fungemia. As the prevalence rises, treatment remains a challenge especially when there is a failure in first-line treatment or drug-resistant fungus. This case report studies a case of chronic EFE, focusing on the diagnostic procedures, treatment options, monitoring parameters and the treatment outcomePatient concerns:A 64-year-old man with underlying well controlled diabetes mellitus was treated with 2 weeks’ course of intravenous antifungal fluconazole for pyelonephritis as his blood culture grew Candida albicans. Concurrently, he complained of 3 months of bilateral painless progressive blurring of vision. At presentation, his visual acuity (VA) was light perception both eyes. Ocular examination revealed non granulomatous inflammation with dense vitritis of both eyes.Diagnosis:He was diagnosed with EFE but the condition responded poorly with the medications.Interventions:He was treated with intravitreal (IVT) amphotericin B and fluconazole was continued. Vitrectomy was performed and intraoperative findings included bilateral fungal balls in the vitreous and retina with foveal traction in the left eye. Postoperatively, vision acuity was 6/24, N8 right eye and 2/60, N unable for left eye with extensive left macular scar and hole. Vitreous cultures were negative. He received multiple IVT amphotericin B and was started on topical steroid eye drops for persistent panuveitis with systemic fluconazole. Ocular improvement was seen after switching to IVT and topical voriconazole. Despite this, his ocular condition deteriorated and he developed neovascular glaucoma requiring 3 topical antiglaucoma agents. Panretinal photocoagulation was subsequently performed.Outcomes:At 3 months’ follow-up, his vision acuity remained at 6/24 for right eye and 2/60 for the left eye. There was no recurrence of inflammation or infection in both eyes.Lessons:Voriconazole could serve as a promising broad spectrum tri-azole agent in cases of failure in first-line treatment or drug-resistant fungus.