Nucleotide mutations associated with hepatitis B e antigen negativity

One hundred and forty four patients with chronic hepatitis B were tested to identify new mutations associated with hepatitis B e antigen (HBeAg) negativity, using a full genome sequence analysis. All the patients were Chinese and had hepatitis B virus infection of genotype C. Patients with none of the pre-core or core promoter mutations were significantly (P < 0.001) less common in the group with anti-HBe (13%) than in the group with HBeAg (56%). The complete nucleotide sequence was determined in four anti-HBe-positive patients who had neither pre-core nor core promoter mutations and in five HBeAg-positive patients who also had neither of these mutations (the groups were matched for age and sex). Six mutations were found to be significantly more common in the former group than in the latter: G529A (3/4 vs. 0/5), C934A (4/4 vs. 1/5), A1053G (4/4 vs. 1/5), G1915T/A (4/4 vs. 0/5), T2005C/A (4/4 vs. 0/5), and C3026T (3/4 vs. 0/5). Three of the six mutations were significantly more common in the four anti-HBe-positive patients who had neither pre-core nor core promoter mutations, compared to 11 HBeAg-positive patients who had pre-core and core promoter mutations, and also compared to 15 anti-HBe-positive patients who had pre-core and core promoter mutations, suggesting further the specificity of these mutations. Of the six mutations, two resulted in amino acid substitution in the polymerase protein, and one is located near the enhancer I region. The results suggest that the six newly discovered mutations are associated with HBeAg negativity.     

Electrical behaviour in a line of anterior pituitary cells (GH cells) and the influence of the hypothalamic peptide, thyrotrophin releasing factor

Anterior pituitary cells of the GH line, which secrete prolactin spontaneously, showed spontaneous action potential activity. Thyrotrophin releasing factor, which increases secretion in these cells, caused a prompt increase of action potential frequency. Potassium, another secretagogue, depolarized the cells and sometimes initiated a burst of action potentials at the onset of this effect. The action potentials persisted in tetrodotoxin-containing and Na-free media, but were suppressed by the Ca-channel blocker, methoxyverapamil. Moreover, elevating the extracellular Ca²⁺ concentration increased the amplitude of the action potentials. These action potentials therefore have a prominent Ca component. This endows them with a particular interest since secretory activity of these cells is known to be dependent on extracellular Ca²⁺. Ba²⁺, which can substitute for Ca²⁺ in maintaining secretion, also substituted for Ca²⁺ in the maintenance of the action potentials. In addition, Ba²⁺ prolonged action potentials remarkably: tetraethylammonium was less effective in this regard.The several parallels between known secretory behaviour and electrical phenomena encourage the view that analysis of electrical activity in anterior pituitary cells may provide useful clues to events involved in stimulus-secretion coupling and in the secretory control exerted by the brain.     

Summation of fibre potentials and the e.m.g.-force relationship during the voluntary movement of a forearm

A linear mathematical model of the electromyogram (e.m.g.) has been developed for the biceps muscle. The number of motor units (and therefore muscle fibres) contributing to the resultant e.m.g. at any stage of movement has been found from the force analysis of elbow flexion. The depths of various motor units and the phase difference between the recruitment of any two motor units have been formulated using a spiral spread of recruitment sequence. The attenuation of individual motor-unit action potentials due to varying depths has been taken into consideration, and due regard has been taken of the length-tension diagram of a muscle while performing the force analysis. Attention has been focused on the flexion of the elbow joint, in which a method of finding the individual contribution of the biceps and brachialis muscles has been developed and applied. The results predicted by the model have been verified by experiments. The model can also be extended to the e.m.g. of other fast skeletal muscles. The conditions and limitations for such generalisations have been stated and discussed.     

Secretory role for human uterodomes (pinopods): secretion of LIF

The differentiation of human endometrial epithelium is a dynamic event, which occurs throughout the menstrual cycle in preparation for pregnancy. The appearance of uterodomes (pinopods) in this regard was first introduced in rodents with an established pinocytotic function, whereas little evidence was available in humans in this context. This study was undertaken to identify the potential physiological roles of uterodomes in the implantation process. To address this, endometrial biopsies from early, mid- and late luteal phases of the menstrual cycle of 23 fertile female patients with regular menses were used. Scanning and transmission electron microscopies (SEM and TEM) as well as immunofluorescence and immunogold TEM were performed to study the morphological changes and the expression pattern of leukaemia inhibitory factor (LIF) at uterodomes. Our results illustrated a high level of LIF expression in the human uterodomes, which was colocalized with the well-known biochemical markers of exocytosis, including syntaxin-1, 25-kDa synaptosomal protein (SNAP-25) and vesicle-associated membrane protein-2 (VAMP-2). Our morphological and immunocytochemical findings illustrated a secretory function for human uterodomes for the first time. In conclusion, this novel function for uterodomes provides an important clue in detection of their physiological function(s) during the process of the plasma membrane transformation.     

Linking DJ-1 to neurodegeneration offers novel insights for understanding the pathogenesis of Parkinson’s disease

Rare monogenic forms of Parkinson's disease (PD) are promoting our understanding of the molecular pathways involved in the common, non-Mendelian forms of the disease. Here, we focus on PARK7, an autosomal recessive form of early-onset parkinsonism caused by mutations in the DJ-1 gene. We first review the genetics of this form and the rapidly expanding knowledge about the structure and biochemical properties of the DJ-1 protein. We also discuss how DJ-1 dysfunction might lead to neurodegeneration, and the implications of this novel piece of information for the pathogenesis of the common PD forms. Although much work remains to be done to clarify the biology of DJ-1, its proposed activity as a molecular chaperone and/or as oxidative sensor appear intriguing in the light of the current theories on the pathogenesis of PD.     

The effect of chronic in vivo infusion of forskolin on noradrenergic receptor sensitivity

The study of in vivo occupancy of benzodiazepine receptors in rat hippocampus and cerebellum indicates that premazepam reaches only about 70% and 80% occupancy respectively within the dose range used for pharmacological tests in rats. Moreover, at equiactive doses (antileptazol ED₅₀), more brain receptors are occupied by premazepam than by other benzodiazepines, suggesting that premazepam may act as a partial agonist at benzodiazepine receptors, with intrinsic activity lower in cerebellum than in hippocampus. These results may explain the lack of sedative and ataxic properties of premazepam.     

Palliative medicine and end of life care in surgery

Surgeons are privileged to offer treatments that often cure disease. Optimizing comfort for those who cannot be cured is also a core part of every clinician's duty: surveys repeatedly tell us that when death is approaching, people value quality of life above length of survival. Recognizing when someone is dying can be difficult. Tools exist to help; it is worth noting that emergency presentation with life-threatening symptoms can be a marker of poor prognosis. Clear, effective communication is crucial: understanding the patient's perspective and expectations is vital before attempting to offer information that allows future care planning. Judicious use of surgery combined with careful prescribing will optimize comfort, allowing the patient to live as well as possible for as long as possible. Anticipatory prescribing includes opioid, anti-emetic, anti-secretory and sedative medication. Attention should also be given to care of the bereaved. Generalists should understand when to refer to specialist palliative care and remember that reflecting on care when someone has died can be beneficial for professional wellbeing.     

不同类型干细胞在缺血性脑卒中治疗中的应用研究进展

目的总结不同类型干细胞移植治疗缺血性脑卒中的研究进展。方法通过检索 PubMed 数据库，总结 2000 年—2020 年不同类型干细胞治疗缺血性脑卒中的研究结果。结果干细胞可经脑实质立体定向移植、外周血、鼻腔、脑脊液等途径移植治疗缺血性脑卒中，主要通过旁分泌和细胞替代两种机制发挥治疗作用。目前对于缺血性脑卒中及其常见并发症的治疗研究主要集中在神经干细胞、胚胎干细胞及 MSCs，这 3 类干细胞各有优缺点，集中反映在干细胞迁移能力、存活率和安全性等方面。目前已有部分干细胞疗法完成了阶段性临床试验。结论干细胞移植治疗缺血性脑卒中可行且具有巨大临床价值，但在干细胞类型的选择、移植策略、迁移能力及存活率等方面，仍存在一些问题亟待解决。     

脂肪来源干细胞在皮肤瘢痕防治领域的研究进展

目的综述脂肪来源干细胞（adipose-derived stem cells，ADSCs）在皮肤瘢痕防治领域的研究进展。方法广泛查阅相关文献，对 ADSCs 预防、治疗皮肤瘢痕形成的体外实验、动物实验及临床研究效果、可能机制以及优化 ADSCs 效果的生物材料进行综述。结果体外、体内实验及临床研究提示 ADSCs 参与皮肤创伤愈合全过程，可能通过减轻炎症反应、促进血管新生，调控 p38/MAPK、过氧化物酶体增殖物激活受体 γ 或 TGF-β₁/Smads 等通路抑制（肌）成纤维细胞活性，减少胶原沉积，从而预防、治疗皮肤瘢痕。生物工程材料，如猪脂肪源基质水凝胶、猪小肠黏膜下层细胞外基质以及人工合成的聚羟基丁酸酯-羟基戊酸盐支架，均有可能进一步提高 ADSCs 防治皮肤瘢痕形成的效能。 结论ADSCs 在皮肤瘢痕防治研究中取得了显著进展，但临床应用途径仍待进一步研究。