Evaluation and Management of Neurogenic Bladder: What Is New in China?

Neurogenic bladder (NB) or neurogenic lower urinary tract dysfunction (NLUTD), a dysfunction of the urinary bladder and urethra due to disease of the central nervous system or peripheral nerves, is a major global medical and social problem. Numerous nervous system abnormalities, such as: stroke, Alzheimer’s and Parkinson’s diseases, traumatic spinal cord injury, spinal cord tumors, congenital spina bifida, and diabetes, can cause NB/NLUTD. There are two major types of bladder control problems associated with NB/NLUTD: the bladder becomes either overactive or underactive depending on the nature, level, and extent of nerve damage. This review specifically focuses on the diagnosis and management of NB/NLUTD in China as well as on recent efforts to treat this disease.     

Peripheral and Central Effects of Melatonin on Blood Pressure Regulation

The pineal hormone, melatonin (N-acetyl-5-methoxytryptamine), shows potent receptor-dependent and -independent actions, which participate in blood pressure regulation. The antihypertensive effect of melatonin was demonstrated in experimental and clinical hypertension. Receptor-dependent effects are mediated predominantly through MT1 and MT2 G-protein coupled receptors. The pleiotropic receptor-independent effects of melatonin with a possible impact on blood pressure involve the reactive oxygen species (ROS) scavenging nature, activation and over-expression of several antioxidant enzymes or their protection from oxidative damage and the ability to increase the efficiency of the mitochondrial electron transport chain. Besides the interaction with the vascular system, this indolamine may exert part of its antihypertensive action through its interaction with the central nervous system (CNS). The imbalance between the sympathetic and parasympathetic vegetative system is an important pathophysiological disorder and therapeutic target in hypertension. Melatonin is protective in CNS on several different levels: It reduces free radical burden, improves endothelial dysfunction, reduces inflammation and shifts the balance between the sympathetic and parasympathetic system in favor of the parasympathetic system. The increased level of serum melatonin observed in some types of hypertension may be a counter-regulatory adaptive mechanism against the sympathetic overstimulation. Since melatonin acts favorably on different levels of hypertension, including organ protection and with minimal side effects, it could become regularly involved in the struggle against this widespread cardiovascular pathology.     

The Interplay between Autonomic Nervous System and Inflammation across Systemic Autoimmune Diseases

The autonomic nervous system (ANS) and the immune system are deeply interrelated. The ANS regulates both innate and adaptive immunity through the sympathetic and parasympathetic branches, and an imbalance in this system can determine an altered inflammatory response as typically observed in chronic conditions such as systemic autoimmune diseases. Rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis all show a dysfunction of the ANS that is mutually related to the increase in inflammation and cardiovascular risk. Moreover, an interaction between ANS and the gut microbiota has direct effects on inflammation homeostasis. Recently vagal stimulation techniques have emerged as an unprecedented possibility to reduce ANS dysfunction, especially in chronic diseases characterized by pain and a decreased quality of life as well as in chronic inflammation.     

Molecular Regulation of Concomitant Lower Urinary Tract Symptoms and Erectile Dysfunction in Pelvic Ischemia

Aging correlates with greater incidence of lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) in the male population where the pathophysiological link remains elusive. The incidence of LUTS and ED correlates with the prevalence of vascular risk factors, implying potential role of arterial disorders in concomitant development of the two conditions. Human studies have revealed lower bladder and prostate blood flow in patients with LUTS suggesting that the severity of LUTS and ED correlates with the severity of vascular disorders. A close link between increased prostatic vascular resistance and greater incidence of LUTS and ED has been documented. Experimental models of atherosclerosis-induced chronic pelvic ischemia (CPI) showed increased contractile reactivity of prostatic and bladder tissues, impairment of penile erectile tissue relaxation, and simultaneous development of detrusor overactivity and ED. In the bladder, short-term ischemia caused overactive contractions while prolonged ischemia provoked degenerative responses and led to underactivity. CPI compromised structural integrity of the bladder, prostatic, and penile erectile tissues. Downstream molecular mechanisms appear to involve cellular stress and survival signaling, receptor modifications, upregulation of cytokines, and impairment of the nitric oxide pathway in cavernosal tissue. These observations may suggest pelvic ischemia as an important contributing factor in LUTS-associated ED. The aim of this narrative review is to discuss the current evidence on CPI as a possible etiologic mechanism underlying LUTS-associated ED.     

Angiotensin II and the Cardiac Parasympathetic Nervous System in Hypertension

The renin–angiotensin–aldosterone system (RAAS) impacts cardiovascular homeostasis via direct actions on peripheral blood vessels and via modulation of the autonomic nervous system. To date, research has primarily focused on the actions of the RAAS on the sympathetic nervous system. Here, we review the critical role of the RAAS on parasympathetic nerve function during normal physiology and its role in cardiovascular disease, focusing on hypertension. Angiotensin (Ang) II receptors are present throughout the parasympathetic nerves and can modulate vagal activity via actions at the level of the nerve endings as well as via the circumventricular organs and as a neuromodulator acting within brain regions. There is tonic inhibition of cardiac vagal tone by endogenous Ang II. We review the actions of Ang II via peripheral nerve endings as well as via central actions on brain regions. We review the evidence that Ang II modulates arterial baroreflex function and examine the pathways via which Ang II can modulate baroreflex control of cardiac vagal drive. Although there is evidence that Ang II can modulate parasympathetic activity and has the potential to contribute to impaired baseline levels and impaired baroreflex control during hypertension, the exact central regions where Ang II acts need further investigation. The beneficial actions of angiotensin receptor blockers in hypertension may be mediated in part via actions on the parasympathetic nervous system. We highlight important unknown questions about the interaction between the RAAS and the parasympathetic nervous system and conclude that this remains an important area where future research is needed.     

miRNA对肝脏糖异生的调控作用

肝脏糖异生过程受神经元和激素系统的严格调节。交感神经系统刺激而副交感神经系统抑制肝脏糖异生。胰岛素刺激糖酵解和脂肪生成,但抑制糖异生;胰高血糖素抵消胰岛素作用。miRNA是一类小非编码RNA,是转录后调节因子,通过靶mRNA降解和翻译抑制来介导其生理作用。最初在秀丽隐杆线虫中有描述,在被发现后,已经在所有脊椎动物类别中鉴定出miRNA,并且已发现一些miRNA以组织特异性方式表达。近年有研究表明,miRNA能特异性调节肝脏糖异生,许多miRNA的下游靶标与糖异生调节直接或间接相关。本文通过阐述miRNA调控糖异生关键酶、相关转录因子和激素等促进或抑制肝脏糖异生的机制,为揭示肝脏糖异生信号分子之间交互作用提供思路。     

Spinal Cord Injury Causes Marked Tissue Rearrangement in the Urethra—Experimental Study in the Rat

Traumatic spinal cord injury (SCI) results in the time-dependent development of urinary impairment due to neurogenic detrusor overactivity (NDO) and detrusor-sphincter-dyssynergia (DSD). This is known to be accompanied by massive changes in the bladder wall. It is presently less clear if the urethra wall also undergoes remodelling. To investigate this issue, female rats were submitted to complete spinal transection at the T8/T9 level and left to recover for 1 week and 4 weeks. To confirm the presence of SCI-induced NDO, bladder function was assessed by cystometry under urethane anesthesia before euthanasia. Spinal intact animals were used as controls. Urethras were collected and processed for further analysis. Following thoracic SCI, time-dependent changes in the urethra wall were observed. Histological assessment revealed marked urethral epithelium reorganization in response to SCI, as evidenced by an increase in epithelial thickness. At the muscular layer, SCI resulted in strong atrophy of the smooth muscle present in the urethral sphincter. Innervation was also affected, as evidenced by a pronounced decrease in the expression of markers of general innervation, particularly those present in sensory and sympathetic nerve fibres. The present data show an evident impact of SCI on the urethra, with significant histological rearrangement, accompanied by sensory and sympathetic denervation. It is likely that these changes will affect urethral function and contribute to SCI-induced urinary dysfunction, and they deserve further investigation.     

Therapeutic Effect of Platelet-Rich Plasma Improves Bladder Overactivity in the Pathogenesis of Ketamine-Induced Ulcerative Cystitis in a Rat Model

The present study attempted to elucidate whether intravesical instillation of platelet-rich plasma (PRP) could decrease bladder inflammation and ameliorate bladder hyperactivity in ketamine ulcerative cystitis (KIC) rat model. Female Sprague Dawley (S-D) rats were randomly divided into control group, ketamine-treated group, ketamine with PRP treated group, and ketamine with platelet-poor plasma (PPP) treated group. Cystometry and micturition frequency/volume studies were performed to investigate bladder function. The morphological change of bladder was investigated by Mason’s trichrome staining. Western blotting analysis were carried out to examine the protein expressions of inflammation, urothelial differentiation, proliferation, urothelial barrier function, angiogenesis and neurogenesis related proteins. The results revealed that treatment with ketamine significantly deteriorated bladder capacity, decreased voiding function and enhanced bladder overactivity. These pathological damage and interstitial fibrosis may via NF-κB/COX-2 signaling pathways and muscarinic receptor overexpression. PRP treatment decreased inflammatory fibrotic biosynthesis, attenuated oxidative stress, promoted urothelial cell regeneration, and enhanced angiogenesis and neurogenesis, thereafter recovered bladder dysfunction and ameliorate the bladder hyperactivity in KIC rat model. These findings suggested that the PRP therapy may offer new treatment options for those clinical KIC patients.     

The underlying mechanisms for development of hypertension in the metabolic syndrome

High blood pressure is an important constituent of the metabolic syndrome. However, the underlying mechanisms for development of hypertension in the metabolic syndrome are very complicated and remain still obscure. Visceral/central obesity, insulin resistance, sympathetic overactivity, oxidative stress, endothelial dysfunction, activated renin-angiotensin system, increased inflammatory mediators, and obstructive sleep apnea have been suggested to be possible factors to develop hypertension in the metabolic syndrome. Here, we will discuss how these factors influence on development of hypertension in the metabolic syndrome.     

城市污水处理A/A/O工艺中溶解氧的自动控制优化设计

为了解决A/A/O工艺污水处理系统在进水负荷波动较大时曝气池中溶解氧(DO)的波动范围大的问题,该文以某A/A/O工艺的污水处理厂作为试运行系统,进行DO的自动控制优化研究,在传统的DO控制方法上加入曝气池的模型算法来进行DO控制的优化设计.试运行系统运行表明该控制方法可以使DO的控制精度范围达到±0.2mg/L.     

Intestinal Homeostasis under Stress Siege

Intestinal homeostasis encompasses a complex and balanced interplay among a wide array of components that collaborate to maintain gut barrier integrity. The appropriate function of the gut barrier requires the mucus layer, a sticky cushion of mucopolysaccharides that overlays the epithelial cell surface. Mucus plays a critical anti-inflammatory role by preventing direct contact between luminal microbiota and the surface of the epithelial cell monolayer. Moreover, mucus is enriched with pivotal effectors of intestinal immunity, such as immunoglobulin A (IgA). A fragile and delicate equilibrium that supports proper barrier function can be disturbed by stress. The impact of stress upon intestinal homeostasis results from neuroendocrine mediators of the brain-gut axis (BGA), which comprises a nervous branch that includes the enteric nervous system (ENS) and the sympathetic and parasympathetic nervous systems, as well as an endocrine branch of the hypothalamic-pituitary-adrenal axis. This review is the first to discuss the experimental animal models that address the impact of stress on components of intestinal homeostasis, with special emphasis on intestinal mucus and IgA. Basic knowledge from animal models provides the foundations of pharmacologic and immunological interventions to control disturbances associated with conditions that are exacerbated by emotional stress, such as irritable bowel syndrome.     

Kinetics and Mechanism of the Cationic Polymerization of Trioxane. III. Copolymerization with Cyclic Formals

Kinetics and mechanism of three cationic copolymerization systems of trioxane (TO) and 1,3-dioxolane (DO) and/or 1,3,5-trioxepane (TOP) including TO/DO 2.0/0.1, TO/DO/TOP 2.0/0.1/0.055, and TO/TOP 2.0/0.1 in a unit of mol/L in 1,2-ethylene dichloride at 30°C were investigated via evaluations of yields of copolymers and conversions of monomer and comonomer(s) using a gravimetric method and gas chromatography, respectively. The reactivity of DO or TOP was higher than that of TO toward the copolymerizations. Two byproducts, namely, TOP (or DO) and tetroxocane (TOC), were formed during the copolymerization of TO and DO (or TOP). The equilibrium concentrations of TO, DO, TOP, and TOC were ca 0.40, 0.02, 0.02, and 0.02 mol/L, respectively, for the TO/DO and TO/TOP systems whereas relatively high equilibrium concentrations of DO and TOP at ca 0.035 mol/L were for the TO/DO/TOP system. As compared with TO homopolymer, the thermal stability of the copolymers was increased with increasing conversion. The finding that the TO/DO/TOP system having a relatively high amount of cyclic formals consumed in the copolymerization exhibited a relatively low thermal stability suggested that the transacetalization reactions proceeded mainly via oxocarbenium species other than cyclic oxonium species, as compared with the TO/DO and TO/TOP systems.     

3,3’-二硝基-4,4’-偶氮氧化呋咱的合成及性能

以丙二酸单酰肼单钾盐为原材料,经硝化和哑硝化反应“一锅法”合成了4-氨基-3-叠氮羰基氧化呋咱(AN-FO),然后通过ANFO合成出3,3 ’-二氨基-4,4’-偶氮氧化呋咱(DAAFO),DAAFO在双氧水/浓硫酸溶液中氧化为DNAFO.用元素分析、IR、MS和DSC-TG对其结构进行了表征.结果表明,丙二酸单肼单钾...     

Complexation Hydrogels for the Oral Delivery of Growth Hormone and Salmon Calcitonin

The hydrogel system of poly(methacrylic acid-co-N-vinyl pyrrolidone) was evaluated for use as an oral delivery system for growth hormone and salmon calcitonin. These proteins were selected because of their therapeutic importance and the insight provided by evaluating the delivery of a therapeutic agent with a high molecular weight (growth hormone) and a drug with a high isoelectric point (salmon calcitonin). Growth hormone loading and release studies were performed for both P(MAA-co-NVP) and P(MAA-g-PEG). Loading efficiencies for the respective systems were 50.9 ± 1.8% and 57.8 ± 4.1%; weight incorporation of the protein was determined to be 3.5 ± 0.1% and 4.0 ± 0.3%. At pH 7.4, growth hormone release of 90% occurred within 45 min for P(MAA-co-NVP) microparticles; 90% release was not achieved with P(MAA-g-PEG) microparticles until 180 min. At pH 1.2, no release occurred from P(MAA-co-NVP) microparticles but 10% release occurred from P(MAA-g-PEG) microparticles. Salmon calcitonin loading and release were shown to be affected by the negative charges of deprotonated MAA; for systems with monomer molar feed ratios of 4:1, 1:1 and 1:4 MAA:NVP, loading efficiencies were determined to be 70.6 ± 3.0%, 25.3 ± 1.2%, and 1.6 ± 1.3%. Salmon calcitonin release was minimal from the copolymer with 4:1 MAA:NVP monomer feed at pH 7.4. The release improved when the pH was raised above physiological levels. These studies confirmed that P(MAA-co-NVP) was an effective oral delivery system for high molecular weight drugs, but improvements are needed before the system could be utilized for high isoelectric point therapeutic delivery.     

Cellular Stress and Molecular Responses in Bladder Ischemia

The concept of bladder ischemia as a contributing factor to detrusor overactivity and lower urinary tract symptoms (LUTS) is evolving. Bladder ischemia as a consequence of pelvic arterial atherosclerosis was first documented in experimental models and later in elderly patients with LUTS. It was shown that early-stage moderate ischemia produces detrusor overactivity, while prolonged severe ischemia provokes changes consistent with detrusor underactivity. Recent studies imply a central role of cellular energy sensors, cellular stress sensors, and stress response molecules in bladder responses to ischemia. The cellular energy sensor adenosine monophosphate-activated protein kinase was shown to play a role in detrusor overactivity and neurodegeneration in bladder ischemia. The cellular stress sensors apoptosis signal-regulating kinase 1 and caspase-3 along with heat shock proteins were characterized as important contributing factors to smooth muscle structural modifications and apoptotic responses in bladder ischemia. Downstream pathways seem to involve hypoxia-inducible factor, transforming growth factor beta, vascular endothelial growth factor, and nerve growth factor. Molecular responses to bladder ischemia were associated with differential protein expression, the accumulation of non-coded amino acids, and post-translational modifications of contractile proteins and stress response molecules. Further insight into cellular stress responses in bladder ischemia may provide novel diagnostic and therapeutic targets against LUTS.     

含硫稳定剂对纳米Ni-P-TiO_2复合镀层形貌与性能的影响

以镀液稳定性、沉积速率、镀层孔隙率、显微硬度和耐蚀性为评价指标,研究了硫代硫酸钠、2-巯基苯并噻唑以及DL-半胱氨酸三种稳定剂对Ni-P纳米TiO_2复合化学镀的影响,研究所采用的基础镀液配方及工艺条件为:26 g/L六水合硫酸镍,32 g/L次亚磷酸钠,15 g/L乙酸钠,20 g/L一水合柠檬酸,10~30 mg/L表面活性剂,1~2 g/L纳米TiO_2,θ为(88±1)℃,pH为4.8±0.2,反应t为1 h。结果表明,硫代硫酸钠对镀层耐蚀性、显微硬度和镀液稳定性的效果都较差,不适合作为本体系的稳定剂;DL-半胱氨酸作为稳定剂时虽然对镀层显微硬度和沉积速率比2-巯基苯并噻唑稍好,但镀液稳定性和镀层耐蚀性不佳。实验表明2-巯基苯并噻唑更适合作为本体系稳定剂,且作为稳定剂时的最佳用量为6.0 mg/L,在该用量下,镀层的沉积速率可达144.6 g/(m^2·h),镀层孔隙率为1.5个/cm^2,显微硬度可达682.5 HV。     

Stellate Ganglia and Cardiac Sympathetic Overactivation in Heart Failure

Heart failure (HF) is a major public health problem worldwide, especially coronary heart disease (myocardial infarction)-induced HF with reduced ejection fraction (HFrEF), which accounts for over 50% of all HF cases. An estimated 6 million American adults have HF. As a major feature of HF, cardiac sympathetic overactivation triggers arrhythmias and sudden cardiac death, which accounts for nearly 50–60% of mortality in HF patients. Regulation of cardiac sympathetic activation is highly integrated by the regulatory circuitry at multiple levels, including afferent, central, and efferent components of the sympathetic nervous system. Much evidence, from other investigators and us, has confirmed the afferent and central neural mechanisms causing sympathoexcitation in HF. The stellate ganglion is a peripheral sympathetic ganglion formed by the fusion of the 7th cervical and 1st thoracic sympathetic ganglion. As the efferent component of the sympathetic nervous system, cardiac postganglionic sympathetic neurons located in stellate ganglia provide local neural coordination independent of higher brain centers. Structural and functional impairments of cardiac postganglionic sympathetic neurons can be involved in cardiac sympathetic overactivation in HF because normally, many effects of the cardiac sympathetic nervous system on cardiac function are mediated via neurotransmitters (e.g., norepinephrine) released from cardiac postganglionic sympathetic neurons innervating the heart. This review provides an overview of cardiac sympathetic remodeling in stellate ganglia and potential mechanisms and the role of cardiac sympathetic remodeling in cardiac sympathetic overactivation and arrhythmias in HF. Targeting cardiac sympathetic remodeling in stellate ganglia could be a therapeutic strategy against malignant cardiac arrhythmias in HF.     

碳酸根基水铝钙石的制备及其在PVC中的应用研究

利用氢氧化钙[Ca(OH)2]和氢氧化铝[Al(OH)3]以及无水碳酸钠（Na2CO3）为原料,以去离子水作溶剂,制备了碳酸根基水铝钙石（Ca4Al2(OH)12CO3·5H2O）,通过傅里叶红外光谱、X射线衍射和扫描电子显微镜表征其结构。并将其作为热稳定剂应用于聚氯乙烯（PVC）中,通过热老化、刚果红、电导率和热失重分析等方法检测其热稳定性能。结果表明,Ca4Al2(OH)12CO3·5H2O具有长期型热稳定剂的特性,当其添加量为3份时,热稳定时间可达70 min,静态热稳定时间可达52 min;当Ca4Al2(OH)12CO3?5H2O/ZnSt2/DMAU复配体系的添加量为3份,并且Ca4Al2(OH)12CO3?5H2O:ZnSt2:DMAU在3：0.5：1.5~3：0：2之间时,复配体系的初期白度可达60 min左右,即使到110 min左右也未观察到“锌烧”现象发生。     

有氧条件下生物过滤法脱氮研究

采用生物过滤法,以醋酸钠为外加碳源,探讨了有氧条件下反硝化脱氮的可行性。研究表明,通过向配制水中通入由N2 O2组成的合成气体,能方便地控制水体中溶解氧的浓度。在向配制水中通入含有少量O2的合成气后,系统中的溶解氧浓度下降比不通任何气体时下降还快。随着溶解氧含量逐渐提升,系统反硝化脱氮效果并未受到明显影响。当溶解氧达到6.4mg/L时,系统仍然具有反硝化作用,只是硝酸盐浓度下降速度比低溶解氧条件下缓慢,但是脱氮效率仍然可达85%左右。结果显示,采用生物过滤系统以及实验室培养得到的两种微生物,在一定溶解氧条件下,溶解氧对系统反硝化脱氮能力影响有限。     

Structural Identification of the Pacemaker Cells and Expression of Hyperpolarization-Activated Cyclic Nucleotide-Gated (HCN) Channels in the Heart of the Wild Atlantic Cod,Gadus morhua (Linnaeus, 1758)

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are proteins that contain highly conserved functional domains and sequence motifs that are correlated with their unique biophysical activities, to regulate cardiac pacemaker activity and synaptic transmission. These pacemaker proteins have been studied in mammalian species, but little is known now about their heart distribution in lower vertebrates and c-AMP modulation. Here, we characterized the pacemaker system in the heart of the wild Atlantic cod (Gadus morhua), with respect to primary pacemaker molecular markers. Special focus is given to the structural, ultrastructural and molecular characterization of the pacemaker domain, through the expression of HCN channel genes and the immunohistochemistry of HCN isoforms, including the location of intracardiac neurons that are adjacent to the sinoatrial region of the heart. Similarly to zebrafish and mammals, these neurons are immunoreactive to ChAT, VAChT and nNOS. It has been shown that cardiac pacemaking can be modulated by sympathetic and parasympathetic pathways, and the existence of intracardiac neurons projecting back to the central nervous system provide a plausible link between them.