Role of the nerve growth factor precursor-neurotrophin receptor p75 and sortilin pathway on apoptosis in the brain of patients with intracerebral hemorrhage

This study demonstrated that brain areas surrounding the site of hematoma following intracerebral hemorrhage are characterized by significantly increased apoptosis and expression of neurotrophin receptor p75 and sortilin. However, as detected by terminal deoxynucleotidyl transferase dUTP nick end labeling and immunohistochemical staining, there was no significant change in nerve growth factor precursor expression levels. The appearance of neurotrophin receptor p75 expressing cells was positively correlated with cells that were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling. These findings confirm that the nerve growth factor precursor-neurotrophin receptor p75-sortilin heterotrimeric complex-mediated apoptosis pathway may play an important role in cellular apoptosis following intracerebral hemorrhage.

Role of Nerve Growth Factor (NGF) and Its Receptor Tyrosine Kinase A (TrK A) in Egyptian Cirrhotic Patients with Pruritus

Background: Pruritus is a distressing symptom of cholestatic, inflammatory, and malignant liver diseases. It is a common symptom in many biliary and cholestatic disorders such as primary biliary cirrhosis (PBC). Several mechanisms are generally accepted as possible explanations to the underlying basis of itch. However, the exact pathophysiology of pruritus in liver diseases remains unclear. The cutaneous and central neurobiology of pruritus is complex and underlies a regulation of variable mechanisms. At present, not all mechanisms including neuromediators and receptors are known. Objective: Our objective is to evaluate whether the expression pattern of NGF and its receptor TrK A has a role in pruritus in a group of Egyptian cirrhotic patients. Patients and Methods: Forty Patients with liver cirrhosis were enrolled in the study depending on clinical evidence of stigmata of chronic liver disease (e.g. jaundice, ascites, palmar erythema, spider naevi, etc.) and ultrasonographic features of liver cirrhosis (e.g. coarse echo texture, shrunken liver, etc.). Patients were divided into two groups. Group (1): included 20 patients cirrhotic patients without pruritus. Group (2): included 20 patients cirrhotic patients with pruritus. A group of age and sex matched healthy twenty volunteers as a control. Results: After evaluation of histopathological using hematoxylin and eosin stained sections (H&E) was done. There was positive correlation between NGF protein expression and severity of pruritus in cirrhotic patients with pruritus (r = 0.876, p value ≤ 0.001). Also there was positive correlation between TrK A protein expression and severity of pruritus in cirrhotic patients with pruritus (r = 0.44, p value ≤ 0.05). Conclusions: We report, for the first time, role of these proteins (NGF/TrK A) in the mechanism of pruritus in cirrhotic patients and may provide a potential target for new treatment of pruritus in cirrhotic.

Expression of nerve growth factor precursor, mature nerve growth factor and their receptors during cerebral ischemia-reperfusion injury

We investigated nerve growth factor precursor （proNGF） and mature NGF expression in ischemic and non-ischemic cortices after cerebral ischemia-reperfusion injury. In both ischemic and non-ischemic cortices, proNGF was found to be present in the extracellular space and cytoplasm. In addition, mature NGF was expressed in extracellular space, but with a very low signal. In ischemic cortex only, proNGF was significantly decreased, reaching a minimal level at 1 day. Mature NGF was increased at 4 hours, then reached a minimal level at 3 days. The p75 neurotrophin receptor （p75NTR） was significantly decreased after ischemia, and increased at 3 days after ischemia. These results confirmed that proNGF was the predominant form of NGF during the pathological process of cerebral ischemia-repeffusion injury. In addition, our findings suggest that ischemic injury may influence the conversion of proNGF to mature NGF, and that proNGF/p75NTR may be involved in reperfusion injury.

Co-expression of estrogen receptor and nerve growth factor in rat intrinsic cardiac ganglia

BACKGROUND： Previous studies have shown that neurons expressing estrogen receptor and nerve growth factor exist in the intrinsic cardiac ganglia in rats. However, it remains to be shown whether estrogen receptor and nerve growth factor are co-expressed within these cells. OBJECTIVE： To determine whether estrogen receptor and nerve growth factor are co-expressed in intrinsic cardiac ganglia. DESIGN, TIME AND SETTING： This cellular morphology observational study was performed at the immunohistochemistry Department, Medicine School, Wuhan University of Science and Technology, between March and July in 2007. MATERIALS： Mouse anti-estrogen receptor and rabbit anti-nerve growth factor polyclonal antibody, biotinylated goat anti-mouse IgG, and biotinylated goat anti-rabbit IgG were provided by Wuhan Boster, China. METHODS： Ten healthy, Wistar rats were included in the present study. Ten sections of intrinsic cardiac ganglia from the atrial posterior wall were randomly selected from each rat to perform estrogen receptor and nerve growth factor double-labeling immunohistochemical staining. MAIN OUTCOME MEASURES： Expression of estrogen receptor and nerve growth factor in intrinsic cardiac ganglia of rats. RESULTS： Immunohistochemistry results demonstrated expression of estrogen receptor and nerve growth factor in rat intrinsic cardiac ganglia, and double-labeling revealed co-expression of estrogen receptor and nerve growth factor in intrinsic cardiac ganglial cells. CONCLUSION： Estrogen receptor and nerve growth factor were shown to be co-expressed in rat intrinsic cardiac ganglial cells.

Clinical significance of nerve growth factor and tropomyosin-receptor-kinase signaling pathway in intrahepatic cholangiocarcinoma

AIM:To investigate the correlation between nerve growth factor-tropomyosin-receptor-kinase(NGF-TrkA)signaling pathway and prognosis in intrahepatic cholangiocarcinoma(IHCC).METHODS:NGF and TrkA expression in 83 samples of IHCC was assessed by immunohistochemistry.Correlations between NGF-TrkA expression and clinicopathological features were analyzed byχ2 test.Moreover,we evaluated the association between NGF-TrkA and overall survival by univariate and multivariate analysis.With experiments in vitro,we investigated the crucial role of NGF-TrkA on proliferation and invasion of IHCC cells with recombinant NGF-βstimulation.RESULTS:We found that NGF and TrkA expression was significantly related with differentiation(P=0.024)and intraneural invasion(P=0.003),respectively.Additionally,double higher expression of NGF and TrkA was identified as an independent prognostic factor in IHCC(P=0.003).Moreover,we demonstrated that NGF-TrkA signaling pathway can promote IHCC proliferation and invasion.CONCLUSION:NGF-TrkA double higher expression is an independent prognostic factor in IHCC.NGF-TrkA pathway can promote IHCC progression,indicating that NGF-TrkA may become a potential drug target.

Expression of estrogen receptor alpha,nerve growth factor,interleukin-2,and androgen receptor in the cerebellum of ovariectomized rats following soybean isoflavone treatment

BACKGROUND： Studies have shown that estrogen receptor alpha （ERα）, nerve growth factor （NGF）, interleukin-2 （IL-2）, and androgen receptor （AR） expression in the cerebellum decreases when estrogen levels decrease in vivo. Soybean isoflavone, a type of non-steroid estrogen with similar molecular structure and function to estradiol, exhibits estrogen-like characteristics. OBJECTIVE： To investigate the effects of various doses of soybean isoflavone on expression of ERa, NGF, IL-2, and AR in the cerebellum of ovariectomized rat, and to determine whether there is a dose-dependent effect.DESIGN, TIME AND SETTING： Controlled trial at the cellular and molecular level. The study was performed at the Experimental Animal Engineering Center, College of Veterinary Medicine, Sichuan Agricultural University from July 2006 to May 2008. MATERIALS： Soybean isoflavone, comprised of daidzin, genistein and isoflavone, was provided by Taiyuan Yuantai Biochemical Industry, China. The ERα, NGF, IL-2, and AR in situ hybridization kit, rabbit anti-rat ERa, NGF, IL-2, and AR monoclonal antibodies, and SABC kit were purchased from Wuhan Boster Biological Technology, China. METHODS： A total of 50 female, Sprague Dawley rats, aged 3 months, were randomly assigned to 5 groups, with 10 animals in each group. With the exception of the sham-operation group （abdominal cavity opening alone）, all rats underwent bilateral ovariectomy. At 14 days after surgery, rats in the high-, middle-, and low-dose soybean isoflavone groups were subcutaneously injected with 1.5, 1.0, and 0.5 mg/kg soybean isoflavone, respectively, every 2 days for 6 consecutive weeks. Rats in the sham-operation and ovariectomized groups were subcutaneously injected with absolute alcohol （0.5 mL/kg）. MAIN OUTCOME MEASURES： Expression levels and distribution of ERα, NGF, IL-2, and AR in the cerebellum were detected by immunohistochemistry and in situ hybridization. RESULTS： Compared with the sham-operation group, immunoreactive products and hybridization signals of ERa, NGF, IL-2, and AR were significantly decreased in the cerebellar cortex and nuclei of ovariectomized rats （P 〈 0.05 or P 〈 0.01）, but increased following soybean isoflavone treatment. In particular, levels of the high-dose soybean isoflavone group were almost restored to levels of the sham-operation group （P 〉 0.05）. The immunoreactive products were primarily located in the cytoplasm and neurites, and rarely in the cell membrane and nuclei. However, the hybridization signals were predominantly located in the nuclei, but rarely in the cytoplasm, cell membrane, or neurites. CONCLUSION： Soybean isoflavone upregulated ERα, NGF, IL-2, and AR protein and gene expression in a dose-dependent manner, and played an important role in sustaining and protecting structure and function of cerebellar neurons. Moreover, the similarity of expression patterns of these molecules indicated that they were mutually interactive during the regulation of soybean isoflavone to the cerebellum.

Distribution of nitric oxide synthase, nerve growth factor receptor and interstitial cells of Cajal in hirschsprung's disease and its significance

Objective To investigate the distribution of nitric oxide synthase (NOS), nerve growth factor receptor (NGFR) and interstitial cells of Cajal (ICCs) in Hirschsprung’s disease (HD). Methods The distribution of NOS, NGFR and ICCs was studied by using NADPH diaphorase histochemistry, immunohistochemistry with a monoclonal antibody to human NGFR and the specific polyclonal antibody against c-kit in 8 normal controls and 10 cases of HD. Results NOS and NGFR were abundantly present in the myenteric plexus and in the nerve fibers of musculature. ICCs were intensively distributed in the surface of circular musculature and around the myenteric plexus to form a network in normal control colon. In contrast, NOS and NGFR were scarce or absent in the myenteric plexus and in the nerve fibers of musculature, while the hypertrophic nerve trunks were NGFR positive, ICCs were scarcely distributed and the network was disrupted in the aganglionic colon in HD. Conclusion These findings suggest the involvement of NOS, NGFR and ICCs in the pathophysiology of HD.

Uncoupling neurotrophic function from nociception of nerve growth factor: what can be learned from a rare human disease?

Nerve growth factor(NGF) is a powerful trophic factor that provides essential support for the survival and differentiation of sympathetic and sensory neurons during development. However, NGF also activates nociceptors contributing significantly to inflammatory pain and neuropathic pain after tissue injury. As such anti-NGF based therapies represent a promising strategy for pain management. Because of dose-dependent serious side effects such as back pain, injection site hyperalgesia, clinical trials of using NGF to treat various disorders such as diabetic neuropathies, chemotherapy-induced and human immunodeficiency virus-associated peripheral neuropathies were all discontinued. Thus far, worldwide clinical applications of NGF in treating patients are very limited except in China. Hereditary sensory autonomic neuropathy type V(HSAN V) is an extremely rare disease. Genetic analyses have revealed that HSAN V is associated with autosomal recessive mutations in NGF. One of the mutations occurred at the 100^(th) position of mature NGF resulting in a change of residue from arginine to tryptophan(R100W). Although those HSAN V patients associated with the NGF^(R100W) mutation suffer from severe loss of deep pain, bone fractures and joint destruction, interestingly patients with the NGF^(R100W) mutation do not show apparent cognitive deficits, suggesting important trophic support function is preserved. We believe that NGF^(R100W) provides an ideal tool to uncouple the two important functions of NGF: trophic versus nociceptive. Studies from investigators including ourselves have indeed confirmed in animal testing that the NGF^(R100W) no longer induced pain. More importantly, the trophic function seemed to be largely preserved in NGF harboring the R100W mutation. On the mechanistic level, we found that the NGF^(R100W) mutation was capable of binding to and signaling through the tyrosine receptor kinase A receptor. But its ability to bind to and activate the 75 kDa neurotrophic factor was significantly diminished. The significance of these findings is at least two folds: 1) the NGF^(R100W) mutation can be used as an alternative to the wildtype NGF to treat human conditions without eliciting pain; and 2) the 75 kDa neurotrophic factor may serve as a novel target for pain management. We will discuss all the details in this mini-review.

Nerve growth factor in muscle afferent neurons of peripheral artery disease and autonomic function

In peripheral artery disease patients,the blood supply directed to the lower limbs is reduced.This results in severe limb ischemia and thereby enhances pain sensitivity in lower limbs.The painful perception is induced and exaggerate during walking,and is relieved by rest.This symptom is termed by intermittent claudication.The limb ischemia also amplifies autonomic responses during exercise.In the process of pain and autonomic responses originating exercising muscle,a number of receptors in afferent nerves sense ischemic changes and send signals to the central nervous system leading to autonomic responses.This review integrates recent study results in terms of perspectives including how nerve growth factor affects muscle sensory nerve receptors in peripheral artery disease and thereby alters responses of sympathetic nerve activity and blood pressure to active muscle.For the sensory nerve receptors,we emphasize the role played by transient receptor potential vanilloid type 1,purinergic P2X purinoceptor 3 and acid sensing ion channel subtype 3 in amplified sympathetic nerve activity responses in peripheral artery disease.

Soluble p75 neurotrophic receptor as a reliable biomarker in neurodegenerative diseases: what is the evidence?

Neurodegenerative diseases are often misdiagnosed,especially when the diagnosis is based solely on clinical symptoms.The p75 neurotrophic receptor(p75^(NTR))has been studied as an index of sensory and motor nerve development and maturation.Its cleavable extracellular domain(ECD)is readily detectable in various biological fluids including plasma,serum and urine.There is evidence for increased p75NTR ECD levels in neurodegenerative diseases such as Alzheimer’s disease,amyotrophic lateral sclerosis,age-related dementia,schizophrenia,and diabetic neuropathy.Whether p75^(NTR) ECD could be used as a biomarker for diagnosis and/or prognosis in these disorders,and whether it could potentially lead to the development of targeted therapies,remains an open question.In this review,we present and discuss published studies that have evaluated the relevance of this emerging biomarker in the context of various neurodegenerative diseases.We also highlight areas that require further investigation to better understand the role of p75^(NTR) ECD in the clinical diagnosis and management of neurodegenerative disorders.

Minocycline inhibits the production of the precursor form of nerve growth factor by retinal microglial cells

A rat model of acute ocular hypertension was established by enhancing the perfusion of balanced salt solution in the anterior chamber of the right eye. Minocycline （90 mg/kg） was administered intraperitoneally into rats immediately after the operation for 3 consecutive days. Immunofluorescence, western blot assay and PCR detection revealed that the expression of the precursor form of nerve growth factor, nerve growth factor and the p75 neurotrophin receptor, and the mRNA expression of nerve growth factor and the p75 neurotrophin receptor, increased after acute ocular hypertension. The number of double-labeled CD11B- and precursor form of nerve growth factor-positive cells, glial fibrillary acidic protein- and p75 neurotrophin receptor-positive cells glial fibrillary acidic protein- and caspase-3-positive cells in the retina markedly increased after acute ocular hypertension. The above-described expression decreased after minocycline treatment. These results suggested that minocycline inhibited the increased expression of the precursor form of nerve growth factor in microglia, the p75 neurotrophin receptor in astroglia, and protected cells from apoptosis.

Vascular endothelial growth factor A promotes platelet adhesion to collagen Ⅳ and causes early brain injury after subarachnoid hemorrhage

The role of vascular endothelial growth factor A in platelet adhesion in cerebral microvessels in the early stage of subarachnoid hemorrhage remains unclear.In this study,the endovascular puncture method was used to produce a rat model of subarachnoid hemorrhage.Then,30 minutes later,vascular endothelial growth factor A antagonist anti-vascular endothelial growth factor receptor 2 antibody,10μg,was injected into the right ventricle.Immunohistochemistry and western blot assay were used to assess expression of vascular endothelial growth factor A,occludin and claudin-5.Immunohistochemical double labeling was conducted to examine co-expression of GP Ⅰa-Ⅱ integrin and type Ⅳ collagen.TUNEL was used to detect apoptosis in the hippocampus.Neurological score was used to assess behavioral performance.After subarachnoid hemorrhage,the expression of vascular endothelial growth factor A increased in the hippocampus,while occludin and claudin-5 expression levels decreased.Co-expression of GP Ⅰa-Ⅱ integrin and type Ⅳ collagen and the number of apoptotic cells increased,whereas behavioral performance was markedly impaired.After treatment with anti-vascular endothelial growth factor receptor 2 antibody,occludin and claudin-5 expression recovered,while co-expression of GP Ⅰa-Ⅱ integrin and type Ⅳ collagen and the number of apoptotic cells decreased.Furthermore,behavioral performance improved notably.Our findings suggest that increased vascular endothelial growth factor A levels promote platelet adhesion and contribute to early brain injury after subarachnoid hemorrhage.This study was approved by the Biomedical Ethics Committee,Medical College of Xi’an Jiaotong University,China in December 2015.

Neurotrophic factor-based pharmacological approaches in neurological disorders

Aging is a physiological event dependent on multiple pathways that are linked to lifespan and processes leading to cognitive decline.This process represents the major risk factor for aging-related diseases such as Alzheimer’s disease,Parkinson’s disease,and ischemic stroke.The incidence of all these pathologies increases exponentially with age.Research on aging biology has currently focused on elucidating molecular mechanisms leading to the development of those pathologies.Cognitive deficit and neurodegeneration,common features of aging-related pathologies,are related to the alteration of the activity and levels of neurotrophic factors,such as brain-derived neurotrophic factor,nerve growth factor,and glial cell-derived neurotrophic factor.For this reason,treatments that modulate neurotrophin levels have acquired a great deal of interest in preventing neurodegeneration and promoting neural regeneration in several neurological diseases.Those treatments include both the direct administration of neurotrophic factors and the induced expression with viral vectors,neurotrophins’binding with biomaterials or other molecules to increase their bioavailability but also cell-based therapies.Considering neurotrophins’crucial role in aging pathologies,here we discuss the involvement of several neurotrophic factors in the most common brain aging-related diseases and the most recent therapeutic approaches that provide direct and sustained neurotrophic support.

Expression of NG2 and platelet-derived growth facto receptor alpha in the developing neonatal rat brain

Platelet-derived growth factor receptor alpha （PDGFRct） is a marker of oligodendrocyte precursor cells in the central nervous system. NG2 is also considered a marker of oligodendrocyte precursor cells. However, whether there are differences in the distribution and morphol- ogy of oligodendrocyte precursor cells labeled by NG2 or PDGFRa in the developing neonatal rat brain remains unclear. In this study, by immunohistochemical staining, NG2 positive （NG2＋） cells were ubiquitous in the molecular layer, external pyramidal layer, internal pyramidal layer, and polymorphic layer of the cerebral cortex, and corpus callosum, external capsule, piriform cortex, and medial septal nucleus. NG2~ cells were stellate or fusiform in shape with long processes that were progressively decreased and shortened over the course of brain development. The distribution and morphology of PDGFRct positive （PDGFRa＋） cells were coincident with NG2＋ cells. The co- localization of NG2 and PDGFRu in the cell bodies and processes of some cells was confirmed by double immunofluorescence labeling. Moreover, cells double-labeled for NG2 and PDGFRa were predominantly in the early postnatal stage of development. The numbers of NG2＋/PDGFRa＋ cells and PDGFRa＋ cells decreased, but the number of NG2＋ cells increased from postnatal days 3 to 14 in the developing brain. In addition, amoeboid microglial cells of the corpus callosum, newborn brain macrophages in the normal developing brain, did not express NG2 or PDGFRu, but NG2 expression was detected in amoeboid microglia after hypoxia. The present results suggest that NG2 and PDGFRct are specific markers of oligodendrocyte precursor cells at different stages during early development. Additionally, the NG2 protein is involved in inflammatory and pathological processes of amoeboid microglial cells.

NGF与TrkA受体在儿童膀胱过度活动症中的研究进展

神经生长因子(NGF)因其在神经细胞的存活、生长以及分化过程中发挥重要作用而得到广泛研究。它分布于机体的各处,根据所结合受体发挥不同的病理生理作用。原肌球蛋白相关激酶A(TrkA)是其高亲和力受体,诸多研究表明NGF在与其结合后,根据其下游不同的信号转导通路而发挥不同作用。NGF与其结合后还对体内发生的其他信号转导通路有交叉影响作用。本文从不同的疾病症状对NGF与TrkA结合后的信号转导通路进行综述,从而探讨NGF/TrkA信号通路在儿童膀胱过度活动症的作用。

基于NGF/PI3K/TRPV1信号通路探究参苓白术散对腹泻型肠易激综合征小鼠的干预机制

目的研究基于神经生长因子/磷脂酰肌醇3-激酶/瞬时受体电位香草酸受体1(NGF/PI3K/TRPV1)信号通路探究参苓白术散对腹泻型肠易激综合征小鼠的干预机制。方法选取40只SPF级SD雄性大鼠,其中空白组10只,模型组13只、研究1组7只、研究2组9只。对照组、模型组只进行生理盐水灌胃,不做其他任何处理。研究1组给予匹维溴铵片20mg/kg水溶液进行灌胃,研究2组给予参苓白术散4g/kg进行灌胃。评估Bristol评分情况;分析脾脏系数、胸腺系数情况;检测IgA、IgG、IgM、IL-1β、IL-6、TNF-α表达水平及NGF/PI3K/TRPV1蛋白表达情况。结果相比于空白组,模型组、研究1组、研究2组Bristol评分、脾脏系数、胸腺系数、IgA、IgG、IgM、IL-1β、IL-6、TNF-α水平及NGF、PI3K、TRPV1蛋白表达均上升(P<0.05);相比于模型组、研究1组,研究2组Bristol评分、脾脏系数、胸腺系数、IgA、IgG、IgM、IL-1β、IL-6、TNF-α水平及NGF、PI3K、TRPV1蛋白表达均下降(P<0.05)。结论参苓白术散抑制NGF/PI3K/TRPV1通路,改善大鼠胃肠功能及大便状态,减轻炎症反应,提高免疫功能稳态情况,干预效果显著。

高血压分子机制及降压靶点的研究进展

高血压是导致脑卒中、心肌梗死、心力衰竭和肾衰竭等发生的危险因素,也是导致死亡的主要原因,因此研究高血压的潜在治疗靶点、开发新的抗高血压药尤为重要。现总结近年来关于高血压新治疗靶点的研究进展,包括Elabela/Apelin-APJ轴、序列相似性家族3D蛋白、成纤维细胞生长因子21和血管紧张素Ⅱ1型受体的变构调节,以期为抗高血压药的研究提供新的思路和文献支持。

Do tensile and shear forces exerted on cells influence mechanotransduction through stored energy considerations?

All tissues in the body are subjected externally to gravity and internally by collagenfibril and cellular retractive forces that create stress and energy equilibrium required for homeostasis.Mechanotransduction involves mechanical work(force through a distance)and energy storage as kinetic and potential energy.This leads to changes in cell mitosis or apoptosis and the synthesis or loss of tissue components.It involves the application of energy directly to cells through integrin-mediated processes,cell-cell connections,stretching of the cell cytoplasm,and activation of the cell nucleus via yes-associated protein(YAP)and transcriptional coactivator with PDZ-motif(TAZ).These processes involve numerous complexes,intermediate molecules,and multiple pathways.Several pathways have been identified from research studies on vertebrate cell culture and from studies in invertebrates.These pathways involve mechanosensors and other molecules that activate the pathways.This review discusses the mitogen-activated protein kinase(MAPK)family,Hippo,Hedgehog,and Wingless-related integration site(WNT)/βcatenin signaling pathways.The mediators covered includeβcatenin,ion channels,growth factors,hormone receptors,members of the Ras superfamily,and components of the linker of nucleoskeleton and cytoskeleton(LINC)complex.However,the interrelationship among the different pathways remains to be clarified.Integrin-mediated mechanotransduction involves direct tensile loading and energy applied to the cell membrane via collagenfibril stretching.This energy is transferred between cells by stretching the cell-cell connections involving cadherins and the WNT/βcatenin pathway.These alterations induce changes in intracellular events in the cytoskeleton and nuclear skeleton caused by the release of YAP and TAZ.These coactivators then penetrate through the nuclear pores and influence nuclear cell function.Alteration in the balance of forces and energy applied to cells and tissues is hypothesized to shift the cell-extracellular matrix mechanical equilibrium by modifying mechanotransduction.The shift in equilibrium can lead to either tissue synthesis,genetic modifications,or promotefibrotic diseases,including epithelial cell-derived cancers,depending on the local metabolic conditions.

桥本甲状腺炎病儿血清肿瘤坏死因子受体相关因子6和神经生长因子受体水平与免疫水平及甲状腺功能的相关性

目的探究桥本甲状腺炎(HT)病儿血清肿瘤坏死因子受体相关因子6(TRAF6)和神经生长因子受体(NGFR)水平与免疫水平及甲状腺功能的相关性。方法选取2021年3月至2022年3月在承德市妇幼保健院就诊的HT病儿104例作为HT组,根据甲状腺功能分为HT亢进组30例,HT正常组38例,HT减退组36例。采用随机数字表法选取同期在儿科门诊体检健康的儿童95例作为对照组。采用酶联免疫吸附测定(ELISA)检测血清辅助型T细胞1(Th1)因子中的白细胞介素2(IL-2)、γ-干扰素(IFN-γ)、辅助型T细胞2(Th2)因子中的白细胞介素4(IL-4)以及TRAF6、NGFR水平;采用Pearson法分析血清TRAF6、NGFR表达以及二者与甲状腺功能指标、炎症因子的相关性。结果HT正常组、HT减退组和HT亢进组TRAF6的表达水平显著高于对照组[(25.12±3.36)µg/L、(28.16±3.48)µg/L、(22.65±3.27)µg/L比(19.25±2.42)µg/L],HT正常组和HT减退组表达水平显著高于HT亢进组,HT减退组显著高于HT正常组(P<0.05);HT正常组、HT减退组和HT亢进组NGFR的表达水平显著低于对照组[(27.36±3.48)µg/L、(25.02±3.42)µg/L、(29.74±3.56)µg/L比(32.04±3.71)µg/L],HT正常组和HT减退组表达水平显著低于HT亢进组,HT减退组显著低于HT正常组(P<0.05);Pearson相关性分析结果显示,HT病人血清中TRAF6和NGFR表达水平呈负相关(P<0.05);与对照组相比,HT组血清中IL-2、IFN-γ、TPOAb、TGAb、游离三碘甲状原氨酸、血清三碘甲状原氨酸、甲状腺素、甲状腺球蛋白水平显著升高,IL-4、游离甲状腺素水平显著降低(P<0.05);Pearson法分析显示,TRAF6水平与IL-2、IFN-γ、TPOAb、TGAb、游离三碘甲状原氨酸、血清三碘甲状原氨酸、甲状腺素、甲状腺球蛋白水平呈正相关,与IL-4、游离甲状腺素水平呈负相关(P<0.05),NGFR水平与IL-4、游离甲状腺素水平呈正相关,与IL-2、IFN-γ、TPOAb、TGAb、游离三碘甲状原氨酸、血清三碘甲状原氨酸、甲状腺素、甲状腺球蛋白水平呈负相关(P<0.05)。结论HT病人血清TRAF6表达水平异常升高,NGFR水平异常降低,均与免疫水平及甲状腺功能相关。

阴部神经电针联合托特罗定治疗女性膀胱过度活动症

目的 研究阴部神经电针联合托特罗定治疗女性膀胱过度活动症(overactive bladder,OAB)的效果。方法 选取2020年4月至2021年5月于浙江中医药大学附属湖州中医院接受治疗的150例女性OAB患者,根据随机数字表法将其分为对照组和研究组,每组各75例。对照组患者使用托特罗定治疗,研究组患者使用阴部神经电针疗法联合托特罗定治疗。比较两组患者的临床症状、排尿症状、尿流动力学指标[最大膀胱测压容量(maximum cystometric capacity,MCC)、最大尿道闭合压(maximum urethral closure pressure,P)_(ura·clos·max)、最大逼尿肌压(maximum detrusor pressure,P_(det·max))、最大尿流率(maximum urine flow rate,Q_(max))]、膀胱功能指标(最初感觉容量、最大尿意容量)、神经生长因子(nerve growth factor,NGF)介导瞬时受体电位(transient receptor potential,TRP)通路指标[NGF、NGF/尿肌酐(urine creatinine,UCr)、TRPV1、TRPV4]及临床疗效。结果 治疗后,研究组患者的夜间排尿次数、尿急次数均显著少于对照组,均次排尿量显著多于对照组(P<0.05)。研究组患者的膀胱过度活动症状评分、视觉模拟评分法评分均显著低于对照组(P<0.05)。研究组患者的MCC、P_(ura·clos·max)显著高于对照组,P_(det·max)、Q_(max)显著低于对照组(P<0.05)。研究组患者的最初感觉容量和最大尿意容量均显著大于对照组(P<0.05)。研究组患者的NGF、NGF/UCr、TRPV1和TRPV4阳性表达率均显著低于对照组(P<0.05)。研究组患者的总有效率显著高于对照组(χ^(2)=5.374,P=0.020)。两组患者的总不良反应发生率比较差异无统计学意义(χ^(2)=0.362,P=0.547)。结论 阴部神经电针疗法联合托特罗定可显著改善女性OAB患者的膀胱功能,抑制临床症状,其可通过抑制NGF介导的TRP通道蛋白TRPV1、TRPV4增高所致的膀胱敏感度发挥作用。