Overview of CF lung pathophysiology

Defects of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) protein affect the homeostasis of chloride, bicarbonate, sodium, and water in the airway surface liquid, influencing the mucus composition and viscosity, which induces a severe condition of infection and inflammation along the whole life of CF patients. The introduction of CFTR modulators, novel drugs directly intervening to rescue the function of CFTR protein, opens a new era of experimental research. The review summarizes the most recent advancements to understand the characteristics of the infective and inflammatory pathology of CF lungs.     

The chondrocyte channelome: A narrative review

Chondrocytes are the main cells in the extracellular matrix (ECM) of articular cartilage and possess a highly differentiated phenotype that is the hallmark of the unique physiological functions of this specialised load-bearing connective tissue. The plasma membrane of articular chondrocytes contains a rich and diverse complement of membrane proteins, known as the membranome, which defines the cell surface phenotype of the cells. The membranome is a key target of pharmacological agents and is important for chondrocyte function. It includes channels, transporters, enzymes, receptors, and anchors for intracellular, cytoskeletal and ECM proteins and other macromolecular complexes. The chondrocyte channelome is a sub-compartment of the membranome and includes a complete set of ion channels and porins expressed in these cells. Many of these are multi-functional proteins with “moonlighting” roles, serving as channels, receptors and signalling components of larger molecular assemblies. The aim of this review is to summarise our current knowledge of the fundamental aspects of the chondrocyte channelome, discuss its relevance to cartilage biology and highlight its possible role in the pathogenesis of osteoarthritis (OA). Excessive and inappropriate mechanical loads, an inflammatory micro-environment, alternative splicing of channel components or accumulation of basic calcium phosphate crystals can result in an altered chondrocyte channelome impairing its function. Alterations in Ca²⁺ signalling may lead to defective synthesis of ECM macromolecules and aggravated catabolic responses in chondrocytes, which is an important and relatively unexplored aspect of the complex and poorly understood mechanism of OA development.     

From the Cover: Salt stress-induced Ca2+ waves are associated with rapid,long-distance root-to-shoot signaling in plants

Their sessile lifestyle means that plants have to be exquisitely sensitive to their environment, integrating many signals to appropriate developmental and physiological responses. Stimuli ranging from wounding and pathogen attack to the distribution of water and nutrients in the soil are frequently presented in a localized manner but responses are often elicited throughout the plant. Such systemic signaling is thought to operate through the redistribution of a host of chemical regulators including peptides, RNAs, ions, metabolites, and hormones. However, there are hints of a much more rapid communication network that has been proposed to involve signals ranging from action and system potentials to reactive oxygen species. We now show that plants also possess a rapid stress signaling system based on Ca²⁺ waves that propagate through the plant at rates of up to ∼400 µm/s. In the case of local salt stress to the Arabidopsis thaliana root, Ca²⁺ wave propagation is channeled through the cortex and endodermal cell layers and this movement is dependent on the vacuolar ion channel TPC1. We also provide evidence that the Ca²⁺ wave/TPC1 system likely elicits systemic molecular responses in target organs and may contribute to whole-plant stress tolerance. These results suggest that, although plants do not have a nervous system, they do possess a sensory network that uses ion fluxes moving through defined cell types to rapidly transmit information between distant sites within the organism.Plants are constantly tailoring their responses to current environmental conditions via a complex array of chemical regulators that integrate developmental and physiological programs across the plant body. Environmental stimuli are often highly localized in nature, but the subsequent plant response is often elicited throughout the entire organism. For example, soil is a highly heterogeneous environment and the root encounters stimuli that are presented in a patchy manner. Thus, factors including dry or waterlogged regions of the soil, variations in the osmotic environment, and stresses such as elevated levels of salt are all likely to be encountered locally by individual root tips, but the information may have to be acted on by the plant as a whole.In animals, long-range signaling to integrate activities across the organism occurs through rapid ionic/membrane potential-driven signaling through the nervous system in addition to operating via long-distance chemical signaling. Plants have also been proposed to possess a rapid, systemic communication network, potentially mediated through signals ranging from changes in membrane potential/ion fluxes (1–3) and levels of reactive oxygen species (ROS) (4, 5) to altered hydraulics in the vasculature (6). Even so, the molecular mechanisms behind rapid, systemic signaling in plants and whether such signals indeed carry regulatory information remains largely unknown. Suggestions that Ca²⁺ channels play a role in signals that occlude sieve tube elements (7), or that mediate systemic electrical signaling (2) in response to remote wounding, highlight Ca²⁺-dependent signaling events as a strong candidate for mediating some of these long-range responses. Similarly, cooling of roots elicits Ca²⁺ increases in the shoot within minutes (8), suggesting systemic signals can elicit Ca²⁺-dependent responses at distal sites within the plant. However, despite extensive characterization of Ca²⁺ signals (reviewed in ref. 9), their roles in a possible plant-wide communication network remain poorly understood. Therefore, to visualize how Ca²⁺ might act in local and systemic signaling, we generated Arabidopsis plants expressing the highly sensitive, GFP-based, cytoplasmic Ca²⁺ sensor YCNano-65 (10). We observed that a range of abiotic stresses including H₂O₂, touch, NaCl, and cold shock triggered Ca²⁺ increases at the point of application. However, NaCl also elicited a Ca²⁺ increase that moved away from the point of stress application. Propagation of this Ca²⁺ increase was associated with subsequent systemic changes in gene expression. We also report that this salt stress-induced long-distance Ca²⁺ wave is dependent on the activity of the ion channel protein Two Pore Channel 1 (TPC1), which also appears to contribute to whole-plant stress tolerance.     

脑外伤患者督脉穴位电刺激fMRI脑成像的初步观察

目的观察脑外伤患者督脉穴位电刺激的fMRI脑成像变化。方法对1例脑外伤患者进行命门穴和腰阳关穴经皮神经电刺激,对穴位刺激时的脑功能变化进行fMRI观察。结果与静息状态比较,电刺激时出现多个脑区激活。结论电刺激督脉可能会影响脑损伤后的神经可塑性过程。     

寰椎椎弓根钉内固定通道的三维CT影像学研究

目的利用三维影像学探讨常人寰椎椎弓根钉内固定通道的解剖学基础。方法从本院PACS系统中随机选取60例头颈部CTA枕寰枢复合体无明确异常的影像学资料,进行回顾性三维CT成像。测量相关解剖学数据,以颈椎扩孔器横截面面积(3~5 mm2)为对照,归纳出3种椎弓根类型。结果 60例头颈部CTA三维图像显示寰椎及周围结构清楚,测量出寰椎椎动脉沟底部后弓外径高度男性(4.39±1.16)mm,女性(3.84±0.84)mm,小于常规螺钉直径(3.50 mm)占27.7%;在寰椎椎弓根通道分型中,Ⅰ型68侧,占56.67%,Ⅱ型25侧,占20.83%;Ⅲ型27侧,占22.50%;皮质骨面积比例随通道面积的减小而增大,在各型椎弓根通道都在80%以上。结论寰椎椎动脉沟底部后弓外径高度是制约寰椎椎弓根钉固定的重要因素,而寰椎椎弓根骨性通道的解剖结构特点则影响置钉技术的选择;设计出适应寰椎椎动脉沟底部后弓外径高度的螺钉是非常必要的。     

经筋排刺法结合皮肤针对脑卒中后上肢偏瘫患者痉挛状态的影响:多中心随机对照研究

ObjectiveTo explore the effect of meridian sinew row needling combined with dermal needling on spasticity of post-stroke patients with upper limb hemiparalysis.MethodsFour hundred and eighty-eight cases of post-stroke patients with upper limb spasticity were randomly divided into two groups at the ratio of 1: 1, the group of meridian sinew row needling combined with dermal needling (group A, 244 cases) and western medication group (group B, 244 cases). Coupled with rehabilitation, the patients in the group A were given meridian sinew row needling combined with dermal needling where five shu points were specifically selected, and three yang meridians of the hand were treated with acupuncture with muscle region, and three yin meridians of the hand were treated with dermal needles; the patients in the group B was treated with conventional western medication with piracetam injection and cerebroprotein hydrolysate included. Clinical efficacy was evaluated among patients in the two groups after three weeks of continuous treatment, and upper limb spasticity and motor functions were observed through modified Asworth Scale and Fugl-Meyer Assessment Scale (FMA) before and after treatment.ResultsFor Asworth Scale, group A was significantly superior to group B (3.04 ± 1.29 vs 3.88 ± 1.54, P<0.05); for FMA scale, group A was also significantly superior to group B (48.67 ± 15.64 vs 42.96 ± 14.72, P<0.05); mitigations of motor status of upper limb joints in group A, such as remission of shoulder adduction (90.5%), pronation of forearm (70.7%), elbow joint flexion (73.1%), wrist joint flexion (80.9%) and finger flexion (88.1%), were superior to those of group B (70.0%, 60.0%, 61.9%, 57.4%, 63.2%, all P<0.05).ConclusionsGood clinical efficacy of the treatment with combined with dermal needling on spasticity of post-stroke patients with upper limb hemiparalysis is achieved.     

Effects of Intermittent Traction Therapy in an Experimental Spinal Column Model

Traction therapy, which is known to be a treatment method for scoliosis, one of many muscles disease, has been used since Hippocrates introduced it. However, the effects of traction therapy are still not clear. In addition, the meridian sinew theory, which is related to muscle treatment and is mentioned in the book on meridian sinews in the Miraculous Pivot of Huangdi's Internal Classic, has not been the subject of much study. For these reasons, experimental spinal models were made for this study to observe and analyze the lengths of vertebral interspaces after intermittent traction therapy, which is known to be excellent among muscle treatment methods, with various tensile forces. The results showed that the effects of intermittent traction therapy were unclear and that it might be harmful, especially when the pain was induced by muscle weakness. Because the results of this study on intermittent traction therapy were different from those expected from osteopathy or craniosacral theory, better studies of the subject are necessary.     

银杏叶片联合钙离子通道阻滞剂治疗高血压病的系统评价

运用Meta分析方法评价银杏叶片联合钙离子通道阻滞剂(CCB)治疗原发性高血压的临床疗效。方法检索PubMed、Cochrane Libray、EMBASE、维普、中国知网数据库(CNKI)、万方数据库、中国生物医学文献服务系统(SinoMed)关于银杏叶片治疗原发性高血压的临床随机对照试验,检索时间从建库以来至2018年9月30日,根据纳入和排除标准共纳入12项研究,1244例患者,使用Review Manager 5.3软件进行Meta分析。结果①银杏叶片联合CCB降压疗效优于单用CCB[OR=4.67,95%CI(3.25,6.71),P<0.00001];②两组收缩压[MD=-11.27,95%CI(-15.32,-7.21),P<0.00001],舒张压[MD=-8.41,95%CI(-8.94,-7.88),P<0.00001];③两组血清一氧化氮(NO)水平[MD=10.62,95%CI(8.48,12.76),P<0.00001],血清内皮素(ET)水平[MD=-1.05,95%CI(-1.31,-0.79),P<0.00001]。结论银杏叶片联合CCB可以提高降压疗效,但纳入研究方法学治疗偏低,可能影响到本研究的可靠性,仍需要高质量的RCT证实。     

有氧运动抑制衰老大鼠脑动脉平滑肌STOC/BKCa功能下调

目的　探讨有氧运动训练对衰老大鼠脑动脉平滑肌细胞全细胞K⁺电流、自发瞬时外向电流及大电导钙激活钾通道生物物理特性的影响。方法　19～21月龄雄性Wistar大鼠12只（老年组）,随机分为安静组和有氧运动组,并选用2月龄Wistar大鼠安静处理作为青年对照组。12周后取脑动脉,急性分离动脉平滑肌细胞。分别采用膜片钳全细胞模式、穿孔膜片钳模式和单通道内面向外模式观察运动对全细胞K⁺电流、自发瞬时外向电流和大电导钙激活钾通道门控特性的影响。结果　安静组全细胞K⁺电流密度及对Iberiotoxin敏感性降低;安静组自发瞬时外向电流幅值降低,频率无明显变化;安静组大电导钙激活钾通道平均开放概率和平均开放时间显著低于青年对照组,而平均关闭时间高于青年对照组;电压依赖性和钙敏感性亦显著下降;与安静组相比,有氧运动可以增加全细胞K⁺电流密度、自发瞬时外向电流幅值及大电导钙激活钾通道平均开放概率、电压依赖性和钙敏感性来实现对大鼠脑动脉平滑肌自发瞬时外向电流/大电导钙激活钾通道功能的保护作用。结论　长期规律有氧运动可以减弱衰老所致的大鼠脑动脉平滑肌细胞大电导钙激活钾通道功能下调,这可能是有氧运动改善衰老动脉功能的重要机制之一。     

Tissue persistence and vaccine efficacy of tricarboxylic acid cycle and one-carbon metabolism mutant strains of Edwardsiella ictaluri

Edwardsiella ictaluri causes enteric septicemia in fish. Recently, we reported construction of E. ictaluri mutants with single and double gene deletions in tricarboxylic acid cycle (TCA) and one-carbon (C-1) metabolism. Here, we report the tissue persistence, virulence, and vaccine efficacy of TCA cycle (EiΔsdhC, EiΔfrdA, and EiΔmdh), C-1 metabolism (EiΔgcvP and EiΔglyA), and combination mutants (EiΔfrdAΔsdhC, EiΔgcvPΔsdhC, EiΔmdhΔsdhC, and EiΔgcvPΔglyA) in channel catfish. The tissue persistence study showed that EiΔsdhC, EiΔfrdA, EiΔfrdAΔsdhC, and EiΔgcvPΔsdhC were able to invade catfish and persist until 11 days post-infection. Vaccination of catfish fingerlings with all nine mutants provided significant (P < 0.05) protection against subsequent challenge with the virulent parental strain. Vaccinated catfish fingerlings had 100% survival when subsequently challenged by immersion with wild-type E. ictaluri except for EiΔgcvPΔglyA and EiΔgcvP. Mutant EiΔgcvPΔsdhC was found to be very good at protecting catfish fry, as evidenced by 10-fold higher survival compared to non-vaccinated fish.