Overcoming the cellular barriers and beyond: Recent progress on cell penetrating peptide modified nanomedicine in combating physiological and pathological barriers

The complex physiological and pathological conditions form barriers against efficient drug delivery.Cell penetrating peptides(CPPs),a class of short peptides which translocate drugs across cell membranes with various mechanisms,provide feasible solutions for efficient delivery of biologically active agents to circumvent biological barriers.After years of development,the function of CPPs is beyond cell penetrating.Multifunctional CPPs with bioactivity or active targeting capacity have been designed and successfully utilized in delivery of various cargoes against tumor,myocardial ischemia,ocular posterior segment disorders,etc.In this review,we summarize recent progress in CPP-functionalized nano-drug delivery systems to overcome the physiological and pathological barriers for the applications in cardiology,ophtalmology,mucus,neurology and cancer,etc.We also highlight the prospect of clinical translation of CPP-functionalized drug delivery systems in these areas.

Are there physiological and pathological convulsive thresholds in brain?

Objective To investigate changes that occur in the brain when the physiological convulsive threshold becomes pathological,and to determine what differences occur in pathological and physiological convulsive thresholds during the development of epilepsy. Methods In this study,the threshold for convulsions was determined by direct cortical stimulation in rats.The convulsive threshold was measured while recording electroencephalograms and subsequently examining histopathological changes in the hippocampus. Results At the beginning of the experiment,convulsive thresholds were all above 1 100 μA although there were significant individual variations in rats of the same group.But those thresholds quickly declined during the initial 4 weeks of repetitive electrical stimulation.The convulsive thresholds approached a constant level[TLS(430±34)μA,TGS(480±46)μA,TPS(605±70)μA]in the 10th week.There were no significant changes in thresholds when stimulation lasted for longer,the convulsive thresholds and the variations in rats of the same group were significantly lower than that at the beginning of the trial(P<0.01).An interictal discharge was also recorded in the 3rd week in heavy current group and at the 8th week in weak current group respectively which were concomitant with the neuronal da-mage and loss in the hippocampus.There was no abnormality observed in control group. Conclusion These findings indicate that the convulsion threshold in the brain should be divided into two stages:physiological convulsive threshold and pathological convulsive threshold(epileptic threshold).Epileptic threshold is created by pathological acquired factors which give rise to brain damage.The intensity of these pathological acquired factors is correlated with the formation of the pathological convulsive threshold.

Differences between physiological and pathological convulsive thresholds in patients with epilepsy

BACKGROUND： Physiological convulsive thresholds degrade when the brain is in some pathologic states; thus, a level of stimulus that cannot provoke a convulsion may evoke a seizure or epileptic seizure. OBJECTIVE： To investigate the changes that occur in the brain when the physiological convulsive threshold becomes pathological, and to determine what differences occur in pathological and physiological convulsive thresholds during the development of epilepsy. DESIGN： A randomized controlled animal experiment. SETTING： Research Institute of Epilepsy of Shanxi Medical University; Department of Neurology, The Third Hospital of Shanxi Medical University; Research Institute of Function of Shanxi Medical University. MATERIALS： Thirty-six female Wistar rats were selected for this study. The rats were obtained from the experimental animal center of Shanxi Medical University. All laboratory procedures complied with animal ethical standards. The animals were randomly divided into three groups： a strong current group, a weak current group and a control group, with 12 rats in each group. An automatic determinator of seizure threshold was made at Shanxi Medical University and Taiyuan University of Technology. Two bipolar stainless steel stimulating electrodes and an electrode connector （diameter 1.2 ram） were made at Taiyuan University of Technology. METHODS： This study was performed in the laboratory of Research Institute of the Epilepsy of Shanxi Medical University between December 2005 and August 2006. The threshold of localized seizures was measured by performing direct cortical stimulation in rats under anesthesia. After 1 week of post-operative recovery, electric stimulation was started with three different kinds of stimulation. Seizure activity was induced by a ramp-shaped single train of biphasic pulses （50 Hz, total pulse duration of 2 ms, increasing from 0 to 2 000μ A in 15 seconds）. The threshold of localized seizures （TLS） has been defined as the minimum current intensity necessary to provoke convulsion of the forelimbs and/or facial muscles. Up to the TLS, if stimulation continued, the current intensity necessary to provoke the generalized seizures is called the threshold of generalized seizures （TGS）. If stimulation is continued for about 2 seconds when the TGS is reached, rats still showed generalized clonic activity after stimulation ceased. When seizures stopped, a short period of immobility can be observed. The current intensity is called the threshold of prolonged seizures （TPS）. The rats in the strong current group were stimulated up to the current level required to reach the TPS. In the course of stimulation, first, the TLS was recorded, then the TGS, and finally the TPS. The stimulation interval in one session was 10 minutes, repeated twice daily. The rats in the weak current group were only stimulated up to the current levels required to reach the TGS; first, the TLS was recorded and then the TGS was measured at the same time as the strong current group. Control animals were also equipped with a full electrode set and placed in the same conditions, but no stimulation took place, only electroencephalogram （EEG） recording at the same times as the experimental groups. MAIN OUTCOME MEASURES： ① Stimulation of the two experimental groups lasted for 11 weeks and then observation of their behavior and electroencephalogram recording continued for 4 weeks. The control group was also observed over a total of 15 weeks. ② Observing neuronal damage/loss in the hippocampus with a light microscope using a 250x visual field. RESULTS： All 36 Wistar rats were included in the final analysis. At the beginning of the experiment, the convulsive thresholds were all above 1 100 μA, although there were significant individual variations among rats of the same group. Those thresholds quickly declined during the initial 4 weeks of repetitive electrical stimulation. The convulsive thresholds approached a constant level in the 10^th week after commencement of stimulation. There were no significant changes in thresholds when stimulations lasted longer; the convulsive thresholds and the variations in rats of the same group were significantly lower than at the beginning of the trial （P 〈 0.01）. An interictal discharge was also recorded in the 3^rd week in the strong current group, and in the 8th week in the weak current group; these discharges were concomitant with neuronal damage and loss in the hippocampus. There was no abnormality observed in the control group. CONCLUSION： These findings indicated that the convulsion threshold in the brain should be divided into two stages： a physiological convulsive threshold and a pathological convulsive threshold （epileptic threshold） The epileptic threshold is created by pathologically acquired factors, which give rise to brain damage. The increase in the intensity of these pathologically acquired factors led to aggravation of damage.

Regulation of pathological blood-brain barrier for intracranial enhanced drug delivery and anti-glioblastoma therapeutics

The blood-brain barrier(BBB)is an essential component in regulating and maintaining the homeostatic microenvironment of the central nervous system(CNS).During the occurrence and development of glioblastoma(GBM),BBB is pathologically destroyed with a marked increase in permeability.Due to the obstruction of the BBB,current strategies for GBM therapeutics still obtain a meager success rate and may lead to systemic toxicity.Moreover,chemotherapy could promote pathological BBB functional restoration,which results in significantly reduced intracerebral transport of therapeutic agents during multiple administrations of GBM and the eventual failure of GBM chemotherapy.The effective delivery of intracerebral drugs still faces severe challenges.However,strategies that regulate the pathological BBB to enhance the transport of therapeutic agents across the barrier may provide new opportunities for the effective and safe treatment of GBM.This article reviews the structure and function of BBB in physiological states,the mechanisms underlying BBB pathological fenestration during the development of GBM,and the therapeutic strategies of GBM based on BBB intervention and medicinal drugs transporting across the BBB.

Emerging roles of astrocytes in blood-brain barrier disruption upon amyloid-beta insults in Alzheimer's disease

Blood-brain barrier disruption occurs in the early stages of Alzheimer’s disease.Recent studies indicate a link between blood-brain barrier dysfunction and cognitive decline and might accelerate Alzheimer’s disease progression.Astrocytes are the most abundant glial cells in the central nervous system with important roles in the structural and functional maintenance of the blood-brain barrier.For example,astrocytic cove rage around endothelial cells with perivascular endfeet and secretion of homeostatic soluble factors are two major underlying mechanisms of astrocytic physiological functions.Astrocyte activation is often observed in Alzheimer’s disease patients,with astrocytes expressing a high level of glial fibrillary acid protein detected around amyloid-beta plaque with the elevated phagocytic ability for amyloid-beta.Structural alte rations in Alzheimer’s disease astrocytes including swollen endfeet,somata shrinkage and possess loss contribute to disruption in vascular integrity at capillary and arte rioles levels.In addition,Alzheimer’s disease astrocytes are skewed into proinflammatory and oxidative profiles with increased secretions of vasoactive mediators inducing endothelial junction disruption and immune cell infiltration.In this review,we summarize the findings of existing literature on the relevance of astrocyte alte ration in response to amyloid pathology in the context of blood-brain barrier dysfunction.First,we briefly describe the physiological roles of astrocytes in blood-brain barrier maintenance.Then,we review the clinical evidence of astrocyte pathology in Alzheimer’s disease patients and the preclinical evidence in animal and cellular models.We further discuss the structural changes of blood-brain barrier that correlates with Alzheimer’s disease astrocyte.Finally,we evaluate the roles of soluble factors secreted by Alzheimer’s disease astrocytes,providing potential molecular mechanisms underlying blood-brain barrier modulation.We conclude with a perspective on investigating the therapeutic potential of targeting astrocytes for blood-brain barrier protection in Alzheimer’s disease.

A Comparative Evaluation of Different Treatment Regimens in Endotoxemic Buffalo Calves—A Physio-Pathological Perspective

Fifteen apparently healthy male buffalo calves aged between 6 months to one year with body weight range of 70 - 140 Kg divided into 3 groups of 5 buffalo calves each were used in the present investigation. Endotoxic shock was produced by IV infusion of Escherichia coli endotoxin @ 5 μg/kg BW/hr for 3 hours followed by administration of three different treatment regimens comprising of intravenous infusion of hypertonic saline solution(HSS) @ 4 ml/Kg bw, flunixin meglumine @ 1.1 mg/Kg bw and blood @ 20 ml/Kg bw to group-I, HSS, Dextran-40 and Flunixin meglumine to group-II and HSS, Dextran-40, whole blood and Flunixin meglumine to group-III with the objectives to study the major physio-pathological changes during induced endotoxemia in buffalo calves and to compare the effects of different treatment options to find out the best treatment option out of the three combinations. All the animals were further observed up to day 2 or death whichever was earlier. Endotoxin infusion to all the animals caused symptoms of restlessness, respiratory distress, snoring, diarrhoea, profuse salivation along with the significant hypoproteinemia, hypoalbuminemia, hypoglobulinemia, hypokalemia and hypocalcemia. The treatment with HSS, flunixin meglumine and blood infused as one time infusion to these endotoxemic buffalo calves not only alleviated the above mentioned symptoms but also significantly raised the circulating albumin level at 5.5 hrs and day 2 and Fibrinogen level at day 2 of observation. A significant hypocalcaemia was observed at 4.5 hours along with an increase in Alkaline Phosphatase at 3.5, 4.5 and 6.5 hrs. All the endotoxemic buffalo calves which died were subjected to post mortem and histopathological studies. Epicardial and endocardial haemorrhages, haemorrhages on intestinal mucosa, congestion, haemorrhages, emphysema and fibrinous thrombi in microvasculature of lungs were salient histopathological findings. On comparison with observations of the other treatment regimens tried, it was found that the IV infusion of the combination of HSS, Flunixin meglumine, Dextran-40 and blood was found to be the most effective leading to full recovery of 3 out of 5 buffalo calves of group-III where as only 1 out of 5 animals recovered in group-II. None of the group-I animals recovered and all of these succumbed to shock after day-2.

薄型子宫内膜的病理生理特征和治疗的研究进展

良好的子宫内膜容受性对成功妊娠至关重要,子宫内膜过薄会导致内膜容受性受损,造成不良妊娠结局。如何治疗薄型子宫内膜、改善内膜容受性、提高胚胎种植率是生殖领域亟需解决的问题。研究薄型子宫内膜的病理生理特征能使临床治疗更具针对性。上皮细胞和巨噬细胞等增殖受损、卵巢类固醇激素及其受体表达减少、细胞外基质过度沉积和细胞衰老等共同参与了薄型子宫内膜的发生和发展。临床治疗薄型子宫内膜的方式较多,如使用雌激素、阿司匹林、他莫昔芬等辅助药物,盆底神经肌肉电刺激,干细胞移植,宫腔灌注粒细胞集落刺激因子和富血小板血浆等,但仍有部分顽固性难治性薄型子宫内膜患者对这些治疗方式反应不佳。现对薄型子宫内膜的病理生理特征及临床治疗进展进行综述。

琼枝白化特征及其附生菌群多样性分析

2021-2022年,海南昌江养殖的琼枝(Betaphycus gelatinae)白化现象频发,造成了一定的经济损失,影响了海洋生态环境。为探究白化琼枝的特征和附生菌群落结构的差异,本研究分析了不同状态琼枝的形态差异;测定了色素含量、光合生理、生理生化等指标;分离、鉴定了不同状态琼枝表面的可培养附生细菌,同时采用16S rRNA高通量测序技术分析了健康琼枝(BgR)和白化琼枝(BgW)表面附生细菌的α多样性、β多样性以及菌群群落结构组成。研究显示,白化琼枝藻体的皮层组织结构遭到破坏,色素含量、最大光合效率(QY_max)显著降低,活性氧(ROS)、超氧化物歧化酶(SOD)、丙二醛(MDA)、脯氨酸(Pro)含量显著降低(p<0.05);BgW的可培养附生细菌数量(2.76×10^(7) cfu/g)显著高于BgR(3.3×10^(4) cfu/g),BgR中可培养附生细菌优势菌为鲁杰氏菌属(Ruegeria),BgW中为Yoonia属;高通量测序结果显示,两组样品附生菌群的α多样性指数无显著差异,但BgW的Ace、Chao、Simpson指数均有所升高,相似性分析(ANOSIM)表明,BgR和BgW表面附生菌群之间存在显著差异,比对注释结果共识别出253个OTUs,无色杆菌属(Achromobacter)、琼脂小杆菌属(Agaribacterium)、Hirschia属、Mesoflavibacter属和Aquimarina属是BgR和BgW之间相对丰度差异最显著的细菌类群(p<0.001);BgR的优势菌群为无色杆菌属,BgW的优势菌群为琼脂小杆菌属。本研究首次报道了白化琼枝的特征及表面附生菌群的变化,为进一步探究琼枝白化的原因奠定了基础。

TBI后应激性肠屏障损害的研究进展

创伤性脑损伤后应激性肠屏障损害增加了患者的死亡风险,严重影响疾病预后,目前其发病机制和治疗策略仍不完全清楚。本文旨在总结创伤性脑损伤应激性肠屏障损害的病理机制和保护策略等关键问题的研究进展,发现肠上皮细胞通透性增加、紧密连接、内质网应激、细胞自噬、缺血再灌注损伤可能是创伤性脑损伤应激后肠屏障损害的主要机制。此外,本文还综述了迷走神经刺激、益生菌、外源性补充饥饿素、氧疗等对创伤性脑损伤后应激性肠屏障损害的保护作用。本文将为探索精准有效的创伤性脑损伤后应激性肠屏障损害防治提供新视角和干预靶点。

眼用药物药代动力学模型研究进展

视力与生活质量息息相关。临床上倾向于使用侵入性较小的外用和全身给药方式治疗青光眼等眼部常见疾病。眼部许多的生理生化屏障包括泪液周转、角膜渗透、血-眼屏障等,限制药物在眼部的渗透与分布,造成眼内药代动力学特征不明确,常用眼部房室模型来描述药物在眼内处置动力学。经典眼房室模型以角膜或玻璃体为中央室,将眼部其他组织整体视为外周室,而基于生理的药代动力学(PBPK)模型则引入眼部血流量变化、转运体对药物转运影响、血-眼屏障等因素,可提供更多药物在眼部的处置细节,有助于辅助眼用新药的开发和指导眼部疾病药物治疗。文章综述了不同给药方式时眼部用药的药代动力学特征,经典房室模型和PBPK模型及其在临床眼部用药方案设计中的应用。

视网膜内界膜的结构和生理功能及其在相关疾病中的作用

内界膜是Müller细胞基底膜、少量胶质细胞组成的半透明均质膜。内界膜组分中的α胶原蛋白、硫酸盐蛋白糖、层粘连蛋白等在视网膜基底膜和视网膜神经血管的发育以及视网膜屏障的形成中发挥着重要作用,其成分结构以及理化性质的病理改变与许多玻璃体视网膜疾病的发生发展息息相关。目前,内界膜剥除术可有效解除残留玻璃体皮质对视网膜的牵拉,预防术后黄斑前膜的生成,被广泛用于内界膜相关疾病,但仍存在视网膜微结构和生理功能受损等问题。因此,多种内界膜改良术也应运而生,包括保留中心凹的内界膜剥除、内界膜翻转、自体内界膜移植等。本文就内界膜的理化性质、生理功能、相关疾病中的病理改变及内界膜相关的手术方式进行综述,旨在加深对内界膜的认识,为临床相关疾病的诊疗提供帮助。

Effects of Maillard reaction and its product AGEs on aging and age-related diseases

Maillard reaction(MR)is a non-enzymatic browning reaction commonly seen in food processing,which occurs between reducing sugars and compounds with amino groups.Despite certain advantages based on Maillard reaction products(MRPs)found in some food for health and storage application have appeared,however,the MR occurring in human physiological environment can produce advanced glycation end products(AGEs)by non-enzymatic modification of macromolecules such as proteins,lipids and nucleic acid,which could change the structure and functional activity of the molecules themselves.In this review,we take AGEs as our main object,on the one hand,discuss physiologic aging,that is,age-dependent covalent cross-linking and modification of proteins such as collagen that occur in eyes and skin containing connective tissue.On the other hand,pathological aging associated with autoimmune and inflammatory diseases,neurodegenerative diseases,diabetes and diabetic nephropathy,cardiovascular diseases and bone degenerative diseases have been mainly proposed.Based on the series of adverse effects of accelerated aging and disease pathologies caused by MRPs,the possible harm caused by some MR can be slowed down or inhibited by artificial drug intervention,dietary pattern and lifestyle control.It also stimulates people's curiosity to continue to explore the potential link between the MR and human aging and health,which should be paid more attention to for the development of life sciences.

皮肤物理屏障的生理基础及修护机制

当前全球皮肤敏感肌问题日益突显,敏感肌护理已成为大众关注的重要护肤命题。皮肤物理屏障作为守护肌肤健康的关键性屏障,此屏障受损是导致敏感肌形成的关键环节。文中阐述了皮肤物理屏障生理结构并总结了对应结构受损时皮肤表现的各种肌肤问题,提出针对皮肤物理屏障三大修护方法,在此基础上描述修护皮肤屏障的几种其他方式,如情绪护肤及温感调节等,旨在为开发修护类化妆品提供理论基础,为搭建敏感肌修护体系赋能。

射血分数保留型心力衰竭的病理生理及治疗药物进展

射血分数保留型心力衰竭在心力衰竭中占40%~71%,是一种涉及心、肾、肺、血管系统和脂肪组织等的多系统疾病,严重影响患者的生活水平。近年来,随着医疗研究水平不断提升,射血分数保留型心力衰竭临床治疗取得一定的效果,但患者仍然存在预后不良情况,复发率升高而生活质量下降。文章通过对射血分数保留型心力衰竭近年国内外相关研究报道进行综述,发现其病理生理机制主要与高血压、冠脉疾病和冠脉微血管功能障碍、左心功能不全、右心室功能障碍和肺动脉疾病、激素系统异常、肥胖、系统性炎症和代谢异常相关,通常使用利尿剂、RAAS抑制剂、SGLT2is、MRA和他汀类药物进行治疗,不同分型的动物模型的构建也为射血分数保留型心力衰竭临床诊治提供一些有价值参考。

Physio-pathology of induced endotoxaemia in bovine and its treatment regimen

Endotoxic shock was induced in five apparently healthy male buffalo calves by i.v infusion of Escherichia coli endotoxin at 5microgram/kilogram (μg/Kg) body weight/hour (BW/hr) for 3 hours. Endotoxin infusion caused clinical signs of restlessness, respiratory distress, snoring, diarrhoea, profuse salivation along with the significant hypoproteinemia, hypoalbuminemia and hypokalemia in all the animals. The animals were observed up to day 4 or death, whichever was earlier. The treatment with one time intravenous infusion of hypertonic saline solution @ 4milliliter/Kilogram body weight (ml/Kg?BW), dextran-40 @ 10 ml/Kg?BW, flunixin meglumine @ 1.1 milligram/Kg?BW (mg/Kg?BW) and blood @ 20 ml/Kg?BW to these animals alleviated the clinical signs and significantly raised the circulating glucose level at 4.5 and 5.5 hrs. The treatment led to survival of three of the five endotoxemic buffalo calves. The significant hypoproteinemia, hypoalbuminemia, hypokalemia and hypoglobulinemia continued even after treatment. Gross and histopathologic findings of congestion, haemorrhage, necrosis in vital organs viz., lungs, liver, kidneys, brain and intestines were suggestive of endotoxin induced hypoxia and multi-organ failure. Additionally, emphysema and fibrinous thrombi in microvasculature of lungs were salient histopathological findings indicating terminal respiratory failure in the remaining two dead endotoxemic buffalo calves. From clinical signs, plasma chemistry and pathological lesions, it was concluded that endotoxemia led to a disruption of critical life processes, but a timely and effective treatment could counter these deleterious effects and save precious lives.

The physiological and pathological mechanisms of early embryonic development

Early embryonic development is a complex process.The zygote undergoes several rounds of division to form a blastocyst,and during this process,the zygote undergoes the maternal-to-zygotic transition to gain control of embryonic development and makes two cell fate decisions to differentiate into an embryonic and two extra-embryonic lineages.With the use of new molecular biotechnologies and animal models,we can now further study the molecular mechanisms of early embryonic development and the pathological causes of early embryonic arrest.Here,we first summarize the known molecular regulatory mechanisms of early embryonic development in mice.Then we discuss the pathological factors leading to the early embryonic arrest.We hope that this review will give researchers a relatively complete view of the physiology and pathology of early embryonic development.

A Commercially Available Skin Care Lotion with a pH of 4.5 and 10% Urea Improves Skin Surface pH, Stratum Corneum Hydration and Epidermal Barrier Function in Subjects with Dry Skin and Atopic Diathesis

OBJECTIVE: The physiological skin surface pH is crucial for several epidermal barrier functions, like stratum corneum integrity, cohesion and restoration. Alterations of the “normal” acidic nature of the skin surface have been shown to correlate with specific skin conditions like aged or inflamed skin and are leading to impaired skin barrier function and formation. It is previously demonstrated that topical acidification in atopic dermatitis improves stratum corneum function, skin barrier structure and clinical signs in dermatitis. Against this background, we examined the impact of a slightly acidic skin care product containing urea on stratum corneum hydration, skin surface pH and epidermal barrier function in subjects with dry skin and atopic diathesis. METHODS: Stratum corneum hydration, skin surface pH and transepidermal water loss were biophysically measured before and after a 4-week treatment period with the test product (pH 4.5, 10% urea) compared to the reference product in 25 volunteers. In addition, dynamic epidermal barrier parameters like stratum corneum integrity, cohesion and recovery were investigated by using a previously described tape stripping approach. RESULTS: It was shown that the test product (pH 4.5, 10% urea) significantly elevated stratum corneum hydration and improved the acidic nature of the skin surface by lowering the skin surface pH to a greater extent compared to the reference product. After the 4-week treatment period a significant faster barrier restoration was detected on the test site treated with the test product compared to the reference product. Moreover, the test product strengthens the skin barrier integrity and cohesion. CONCLUSION: The present marketed skin care lotion was shown to increase epidermal barrier function after 4 weeks of application. Balancing and controlling the skin surface pH in subjects with dry and atopic-prone skin by application of the herein tested o/w emulsion with a given pH of 4.5, in combination with a 10% urea content seems to be effective and beneficial. The results are important for the formulation of topical products for dry and atopic-prone skin.

Mimicking the native bone regenerative microenvironment for in situ repair of large physiological and pathological bone defects

Bone is a complex biological tissue with a complicated hierarchical nanocomposite structure.The native microen-vironment of the bone tissue may be significantly disrupted by large physiological and pathological bone defects.Bone defects are often treated via complex surgical procedures that involve the application of autografts or al-lografts.While these grafting procedures often suffer from insufficient natural bone stock and immunorejection.Moreover,these traditional treatment methods fail to simulate a regenerative microenvironment,which plays a significant role in regeneration of bone tissue and repair of large bone defects.To this end,various biomimetic scaffolds have been devised to mimic the native microenvironment of bone and thereby to simultaneously re-pair bone defects and promote bone regeneration.We propose here a novel concept,in vivo bone regenerative microenvironment(BRM),which enables repair of large bone defects and enhances new bone tissue formation with external regulation.In this review,we mainly focus on materials and methods for fabrication of biomimetic scaffolds,as well as their therapeutic efficacy in modulating the BRM of large physiological and pathological bone defects.

肾与心力衰竭相关性的研究进展

心力衰竭是一种常见疾病,是多种心血管疾病的终末阶段,中医上属“心悸”“喘证”范畴,临床多表现心悸、气喘、水肿等。肾为一身阴阳之本,百病之极,穷必及肾,心力衰竭亦受肾变化的影响。现代研究发现,肾功能损伤可通过神经激素系统调节、炎症反应、氧化应激等病理环节参与心力衰竭的发生、发展。因此,认识肾与心力衰竭的相互联系在临床诊治中尤为重要。现基于“心肾相交”理论,阐述肾与心的关系,认为肾与心力衰竭具有相关性。从中西医角度,分析肾的生理功能和病理变化,即肾主水、肾主纳气及肾气、肾阴和肾阳亏虚对心力衰竭的影响,研究肾功能损伤与心力衰竭的相互作用,重新梳理心力衰竭的病机,为临床诊疗提供新思路。

从整体观论治经筋病

整体观是中医理论体系中的核心内容之一。目前对于经筋病的治疗囿于“以痛为输”,缺乏整体观念。筋作为人体组织结构的基础,不是孤立存在的,通过“经”有规律地联系在一起。经筋理论是由局部上升到整体的高度总结,其构成、分布循行与现代的肌筋膜链高度重合,为经筋“束节络骨,利全体之运动”“点-线-面-体”的运动规律打下基础,即经筋生理功能具有整体性。经筋结构、功能的整体性决定了其病理变化的整体性,由结筋病灶点产生,引发远端病变,最终破坏人体平衡,出现整体姿势异常。经筋病的治疗根据“整体-局部-整体”的影响规律,通过望整体姿势判断目标肌肉,使用针刺手法松解局部筋结,恢复正常整体姿势,则全身气血运行通畅,疼痛得以缓解,疗效立竿见影。