心房Ca~(2+)稳态与心房颤动的发生机制

心肌细胞内Ca2+稳态异常是心房颤动发生的重要因素。FK506结合蛋白12.6调控RyR2的异常导致Ca2+漏出,受磷蛋白表达过高时对肌质网钙摄取通道Ca2+ATP酶的过度调控以及心房细胞L型钙电流的下调都是导致心房Ca2+稳态异常的机制,心房钙调控的一些关键部位则可能成为房颤治疗的靶点。心房内Ca2+稳态受钙释放通道、SERCA2a、L型钙通道等的调控,现就目前房颤发生机制的分子机制予以综述。     

Anti-cancer drugs interfere with intracellular calcium signaling

(Neuro-)toxicity of metal and metal compounds is frequently highlighted. While specific metals or metal compounds are essential for cellular function, other metals are toxic and/or carcinogens. Metals can trigger accidental cell death in the form of necrosis, or activate programmed cell death in the form of apoptosis.The aim of anti-cancer therapy is induction of apoptosis in tumor cells. Therefore, there is an interesting twist in the toxicity of metals and metal compounds (e.g., arsenic trioxide, cisplatin); since they have a higher specificity to induce apoptosis in cancer cells (possibly due to the high turnover in these cells) they are used to cure some forms of cancer.A body of evidence suggests that second messengers, such as modulations in the intracellular calcium concentration, could be involved in metals induced toxicity as well as in the beneficial effects shown by anti-cancer drugs.Here we review the influence on calcium homeostasis induced by some metallic compounds: cisplatin, arsenic trioxide and trimethyltin chloride.     

阴茎阴囊 Paget 病局部扩大切除术与根治性切除术的比较研究

目的通过与根治性切除术比较，评价阴茎阴囊 Paget 病局部扩大切除术的疗效。方法回顾性分析 2010 年 11 月—2015 年 8 月收治并符合选择标准的 41 例阴茎阴囊 Paget 病患者临床资料，其中 14 例采用局部扩大切除术（A 组），27 例采用根治性切除术（B 组）。两组患者年龄、病程、病损部位等一般资料比较，差异均无统计学意义（P>0.05），具有可比性。记录并比较两组复发率、手术时间、术中快速冰冻病理检查次数、术后住院时间、创面愈合分级、患者功能及外观自评满意度评分。 结果与 B 组比较，A 组手术时间、术后住院时间均显著缩短，术中快速冰冻病理检查次数减少，比较差异均有统计学意义（P<0.05）。两组患者均获随访，A 组随访时间为 13～67 个月，平均 35.5 个月；B 组 11～70 个月，平均 38.8 个月。A 组创面甲级愈合 11 例、乙级愈合 2 例、丙级愈合 1 例，B 组分别为 12、7、8 例，两组比较差异有统计学意义（Z=–2.102，P=0.036）。术后 5 年内 A 组复发 4 例（28.6%），B 组复发 6 例（22.2%），比较差异无统计学意义（χ²=0.202，P=0.654）。末次随访时，A 组患者外观及功能自评满意度评分显著高于 B 组，比较差异有统计学意义（t=–2.810，P=0.008）。 结论阴茎阴囊 Paget 病进展缓慢，预后良好，局部扩大切除术可有效去除症状，降低老年患者围手术期风险，且术后复发率较根治性切除术未明显升高。     

Disease or adaptation: another look at the practice of medicine

The practice of medicine has changed considerably over the past few decades and is now focusing more and more on early intervention strategies. As a result, we tend to consider pre-symptomatic abnormalities, however small, already as a potential target for treatment. In this viewpoint, we argue that we should put more emphasis on pathophysiological thinking as many of the so-called early abnormalities may, in fact, reflect adaptive mechanisms rather than disease. This view should influence medical care and education, emphasizing the importance of knowledge of pathophysiology.     

中药治疗心血管疾病中线粒体氧化应激损伤的研究

线粒体是真核细胞中最重要的细胞器之一,是除细胞核以外唯一含有遗传物质的细胞器.在有氧呼吸过程中线粒体或多或少会产生活性氧,而活性氧积聚过多则会导致线粒体功能紊乱,参与各种疾病的发生与发展.随着我国对中医药事业的大力支持与深入挖掘,发现大量中药的疗效机制或与线粒体相关.     

Disturbance of thermal homeostasis during post-exercise hyperthermia

The response of core temperature to exercise was investigated during recovery in order to avoid the antagonistic competition between exercise and thermal reflexes for the same effector systems which control skin blood flow. Five healthy, non-training males [mean (SD) age, 23.8 (2.04) years] were habituated to 29° C at relative 50% humidity for more than 2 h and then exercised by treadmill running at about 75% maximum oxygen uptake for 18 min. They then remained at 29° C for up to 65 min of recovery. Oesophageal (T _es), rectal (T _re) and skin temperatures (T _sk) were recorded at 5-s intervals throughout. The abrupt fall of temperature gradient from the forearm to finger was used to identify the T _es for skin vessel dilatation (T _dil) during exercise. Mean (SE) Ts rose from a resting value of 36.67 (0.15)° C to 38.22 (0.24)° C, mean T _re rose from 37.09 (0.25)° C to 38.23 (0.15)° C, and T _dil occurred at 37.39 (0.32)° C. Within 10 min of recovery mean T _es fell to 37.31 (0.24)° C, where it remained a significant 0.64° C above its pre-exercise (PrEx) level (P0.018) but insignificantly different from T _dil for the remaining 55 min of recovery. Meanwhile, T _re fell gradually throughout recovery to 37.64 (0.18)° C. The T _sk at all non-acral sites except the thigh had recovered to PrEx levels by 20–30 min post-exercise (PoEx). The rapid PoEx fall of T _es to the level of T _dil and the subsequent plateau above PrEx values suggests that heat dissipation during recovery was primarily passive once T _es had fallen to T _dil, even though T _es and T _re were significantly elevated. The relationship of these results to the set-point and load error concepts of thermal control is discussed.These data have been presented at the Canadian Physiological Society Winter meeting, January 1993, but have not been previously published     

Small leucine‐rich proteoglycans (SLRPs): characteristics and function in the intervertebral disc

The intervertebral disc (IVD) is responsible for normal spinal motion and load distribution. However, degeneration may occur due to age‐ and non‐age‐related processes and is primarily characterized by a reduction in the number of chondrocyte‐like cells and abnormal extracellular matrix (ECM) structure in the nucleus pulposus. Although IVD progenitor cells have been identified, the local microenvironment components regulating the behaviour of these progenitor cell populations remain unknown. Small leucine‐rich proteoglycans (SLRPs) are bioactive components of the ECM associated with fibrillogenesis, cellular growth and apoptosis and tissue remodelling. SLRPs support the survival of IVD progenitor cells under hypoxic conditions via the activation of specific hypoxia‐inducible factors. Additionally, SLRPs deficiency (biglycan) in knockout mice is sufficient to accelerate the IVD degenerative process. These data suggest that SLRPs play an important role in the homeostasis of IVD. Given their specific properties and physiological functions, we propose a role of SLRPs in IVD degeneration and potential application in its regeneration. Copyright © 2015 John Wiley & Sons, Ltd.