荷兰《医学文摘》中文教材辨异及思考

#本文以荷兰《医学文摘》(EM)原始材料.即自创刊以来的各分册各卷各期以及有关EM的各种书刊为依据,将所能收集到的EM中文教材及有关EM的学术论文进行横向比较,进行辨异思考、指出存在的七大问题。并且提出编写教材应补充新内容,提供新信息和应以原始材料为依据,其它资料为参考的两原则。

谈俄文医学文献检索课教学

本文对医学院校俄文医学文献检索课现状、教学内容、教材、授课对象和教学方式进行了分析与讨论,指出了加强俄文医学文献检索课教学的重要性和改进措施.

住院医师文献检索课教学的探讨

住院医师的培养是整个医学生毕业后教育的重要组成部分,是稳定我国住院医师队伍,加强医院人才建设,提高医疗质量的重要措施。

重视四大检索刊的对比 提高检索室的辅教功能

高等医学院校图书馆文献检索室,是以美国《化学文摘》、美国《医学索引》、荷兰《医学文摘》、美国《生物学文摘》这四种刊物为其主要检索刊,本文对这四种刊物的特色进行了综合对比。

未来的避孕方法

未来的避孕方法据英国《医学文摘》报道，未来的避孕疫苗主要目的是：１．提供安全持久的避孕；２．有利于与防病疫苗服务机构相结合。避孕疫苗在人体中作用的环节有两方面：胚胎在子宫内植入和胎儿生长发育过程，可以看出有显然不同，其是一防止受孕，其二是防止怀孕发展...

Immune response after photodynamic therapy increases anti-cancer and anti-bacterial effects

Photodynamic therapy(PDT) is a clinically approved procedure for treatment of cancer and infections. PDT involves systemic or topical administration of a photosensitizer(PS), followed by irradiation of the diseased area with light of a wavelength corresponding to an absorbance band of the PS. In the presence of oxygen, a photochemical reaction is initiated, leading to the generation of reactive oxygen species and cell death. Besides causing direct cytotoxic effects on illuminated tumor cells, PDT is known to cause damage to the tumor vasculature and induce the release of pro-inflammatory molecules. Pre-clinical and clinical studies have demonstrated that PDT is capable of affecting both the innate and adaptive arms of the immune system. Immune stimulatory properties of PDT may increase its beneficial effects giving the therapy wider potential to become more extensively used in clinical practice. Be-sides stimulating tumor-specific cytotoxic T-cells capable to destroy distant untreated tumor cells, PDT leads to development of anti-tumor memory immunity that can potentially prevent the recurrence of cancer. The immunological effects of PDT make the therapy more effective also when used for treatment of bacterial infections, due to an augmented infiltration of neutrophils into the infected regions that seems to potentiate the outcome of the treatment.

Role of myeloid-derived suppressor cells in autoimmune disease

Myeloid-derived suppressor cells(MDSCs) represent an important class of immunoregulatory cells that can be activated to suppress T cell functions. These MDSCs can inhibit T cell functions through cell surface interactions and the release of soluble mediators. MDSCs accumulate in the inflamed tissues and lymphoid organs of patients with autoimmune diseases. Much of our knowledge of MDSC function has come from studies involving cancer models, however many recent studies have helped to characterize MDSC involvement in autoimmune diseases. MDSCs are a heterogeneous group of immature myeloid cells with a number of different functions for the suppression of T cell responses. However, we have yet to fully understand their contributions to the development and regulation of autoimmune diseases. A number of studies have described beneficial functions of MDSCs during autoimmune diseases, and thus there appears to be a potential role for MDSCs in the treatment of these diseases. Nevertheless, many questions remain as to the activation, differentiation, and inhibitory functions of MDSCs. This review aims to summarize our current knowledge of MDSC subsets and suppressive functions in tissue-specific autoimmune disorders. We also describe the potential of MDSC-basedcell therapy for the treatment of autoimmune diseases and note some of hurdles facing the implementation of this therapy.

Apoptotic signaling through reactive oxygen species in cancer cells

Reactive oxygen species(ROS) take part in diverse biological processes like cell growth,programmed cell death,cell senescence,and maintenance of the transformed state through regulation of signal transduction. Cancer cells adapt to new higher ROS circumstance. Sometimes,ROS induce cancer cell proliferation. Meanwhile,elevated ROS render cancer cells vulnerable to oxidative stress-induced cell death. However,this prominent character of cancer cells allows acquiring a resistance to oxidative stress conditions relative to normal cells. Activated signaling pathways that increase the level of intracellular ROS in cancer cells not only render up-regulation of several genes involved in cellular proliferation and evasion of apoptosis but also cause cancer cells and cancer stem cells to develop a high metabolic rate. In over the past several decades,many studies have indicated that ROS play a critical role as the secondary messenger of tumorigenesis and metastasis in cancer from both in vitro and in vivo. Here we summarize the role of ROS and anti-oxidants in contributing to or preventing cancer. In addition,we review the activated signaling pathways that make cancer cells susceptible to death.

Vestibular evoked myogenic potential

Vestibular evoked myogenic potential （VEMP）, is an electromyographic response of vestibular origin evoked by sound, vibration or electrical stimulation. VEMP is widely used as a clinical test of the otolith organs. Now-adays, two kinds of VEMP, cervical VEMP （cVEMP） and ocular VEMP （oVEMP） are clinically used. cVEMP is a test of sacculo-collic refex while oVEMP is a test of utri-culo-ocular refex. Absence of responses, large interau-ral asymmetry of amplitudes, prolonged peak latencies, and abnormal thresholds of responses are regarded as abnormal responses. Clinical application to various diseases of the vestibular system was performed. Using VEMP, a new type of vestibular neuritis, inferior ves-tibular neuritis was established. A prominent feature of VEMP in Meniere’s disease is a shift of a preferred fre-quency in cVEMP. The whole aspects of VEMP fndings in patients with benign paroxysmal positional vertigo are not clarifed yet. Sensitivity of cVEMP to vestibular schwannoma was 80.0%, while specifcity was 52.7%. Concerning diagnosis of superior canal dehiscence syn-drome （SCDS）, oVEMP to air-conducted sound is the most helpful. Augmentation of oVEMP responses is a prominent feature in SCDS. I also presented “idiopathic otolithic vertigo”, which I proposed as a new clinical en-tity based on VEMP fndings. Some patients complained of lateral tilting sensation in the roll plane, or tilting or translational sensation in the pitch plane without rota-tory vertigo. Majority of patients with these symptoms had absent or decreased responses of oVEMP and/or cVEMP. I proposed that these patients could be diag-nosed as having “idiopathic otolithic vertigo”.

Noise-induced hearing loss in the 21^(st) century: A research and translational update

Millions of people worldwide are exposed to harmful levels of noise daily in their work and leisure environment. This makes noise-induced hearing loss(NIHL) a major occupational health risk globally. NIHL is the second most common form of acquired hearing loss after agerelated hearing loss and is itself a major contributing factor to presbycusis. Temporary threshold shifts, once thought to be relatively harmless and recoverable, are now known to cause permanent cochlear injury leading to permanent loss of hearing sensitivity. This article reviews the current understanding of the cellular and molecular pathophysiology of NIHL with latest findings from animal models. Therapeutic approaches to protect against or to mitigate NIHL are discussed based on their proposed action against these known mechanisms of cochlear injury. Successes in identifying genes that predispose individuals to NIHL by candidate gene association studies are discussed with matched gene knockout animal models. This links to exciting developments in experimental gene therapy to replace and regenerate lost hair cells and post-noise otoprotective therapies currently being investigated in clinical trials. The aim is to provide new insights into current and projected future strategies to manage NIHL; bench to bedside treatment is foreseeable in the next 5 to 10 years.

Extended pectoralis major myocutaneous flap in head and neck reconstruction

Although the pectoralis major myocutaneous flap is often used in head and neck reconstruction, the extension of the skin paddle beyond the inferior limits of the muscle has not been well described. We aim to clarify the design and application of this extended flap in head and neck reconstruction. In this retrospective study, consecutive cases of extended pectoralis major myocutaneous flap reconstruction of post-ablative head and neck defects at a single tertiary referral center were included for analysis. In 7 cases an extended pectoralis major flap was utilized, in which the skin paddle was extended beyond the inferior border of the pectoralis major to include the rectus sheath. Skin and soft tissue as well as composite defects of the oral cavity, parotid/temporal region and neck were reconstructed. All flaps healed satisfactorily with no loss of skin viability. The extended pectoralis major myocutaneous flap is robust and has versatile applications for reconstruction of large, high and three dimensionally complex defects in the head and neck region.

Noise-induced cochlear inflammation

Hearing loss is the most common sensory disability with considerable social and economic implications. According to recent World Health Organization estimates,360 million people worldwide suffer from moderate to profound hearing loss. Exposure to excessive noise is one of the major causes of sensorineural hearing loss,secondary only to age-related hearing loss(presbyacusis). Since cochlear tissues have limited abilities of repair and regeneration, this damage can be irreversible, leading to cochlear dysfunction and permanent hearing loss. Recent studies have shown that cochlear inflammation can be induced by noise exposure and contribute to the overall pathogenesis of cochlear injury and hearing loss. The cochlea is separated from the systemic circulation by the blood-labyrinth barrier,which is physiologically similar to the blood-brain barrier of the central nervous system. Because of this feature, the cochlea was originally considered an immunologically privileged organ. However, this postulate has been challenged by the evidence of an inflammatory response in the cochlea in the presence of bacterial or viral pathogens or antigens that can cause labyrinthitis. Although the main purpose of the inflammatory reaction is to protect against invading pathogens, the inflammatory response can also cause significant bystander injury to the delicate structures of the cochlea. The cochlear inflammatory response is characterised by the generation of proinflammatory mediators(cytokines, chemokines and adhesion molecules), and the recruitment of inflammatory cells(leukocytes). Here, we present an overview of the current research on cochlear inflammation, with particular emphasis on noise-induced cochlear inflammation. We also discuss treatment strategies aimed at the suppression of inflammation, which may potentially lead to mitigation of hearing loss.

Eotaxin-2 blockade ameliorates experimental autoimmune encephalomyelitis

AIM： To study the effect of blocking the eo-2 pathwaon the development and severity of experimental autoimmune encephalomyelitis （EAE）. METHODS： We produced mAb directed against eo-2named D8. MOG35-55 induced-EAE mice were dailintravenously injected with either 25 μg or 100 μg D8or with vehicle control alone [phosphate-buffered saline（PBS）], starting from day 0 post immunization and weremonitored for EAE clinical score （n = 10 in each group）Mice were sacrifced on day 58 and their sera were assessed for the presence of anti-myelin oligodendrocyteglycoprotein （anti-MOG） antibodies autoantibodies, awell as for the profle of pro-infammatory cytokines andchemokines. Histological analysis of brain sections waperformed by hematoxylin and eosin staining.RESULTS： Daily treatment of EAE induced mice with D8 signifcantly decreased the severity of EAE symp-toms. Treatment with both concentrations of D8 ame-liorated EAE symptoms compared to PBS treated mice, starting from day 42 post immunization （0.89 ± 0.35 in D8 25 μg and D8 100 μg treated groups vs 2.11 ± 0.38 in the PBS treated group, P = 0.03）. A signifcant im-provement in EAE clinical score compared to total IgG treated mice was observed with the higher concentra-tion of D8 （0.81 ± 0.38 in D8 100 μg treated group vs 2.11 ± 0.31 in IgG1 treated group, on day 56 post immunization, P = 0.04）. D8 treated mice with EAE did not signifcantly exhibit lower sera levels of anti-MOG autoantibodies compared to IgG-treated mice. How-ever, they expressed lower sera levels of the pro-in-fammatory cytokines： tumor necrosis factor （7.8 ± 0.2 pg/mL in D8 100 μg treated mice vs 19.9 ± 3.4 pg/mL in IgG treated mice, P = 0.005） and interferon-gamma （1.4 ± 0.6 pg/mL in D8 100 μg treated mice vs 3.6 ± 0.4 pg/mL in IgG treated mice, P = 0.02）, as well as reduced levels of the chemokine macrophage che-moattractant protein-1 （27.2 ± 3.1 pg/mL in D8 100 μg treated mice vs 63.7 ± 12.3 pg/mL in IgG treated mice, P = 0.03）. These fndings indicate that blocking the eo-2 pathway in EAE may affect not only eosino-phil infltration into the central nervous system （CNS）, but also have an effect on monocytes and T cells, but not humoral, mediated responses. Histological analysis of the brains of D8 treated mice with EAE support that this treatment decreases immune cells infltrates in the CNS.CONCLUSION： Taken together, these fndings suggest a role for eo-2 in EAE pathogenesis and consequen-tially may support a therapeutic potential of anti-eo-2 neutralizing mAb in multiple sclerosis.

Circulating immune cell activation and diet: A review on human trials

Protein energy malnutrition is the main cause of immunodeficiency and, secondarily, of several infections. However, immune cell activation is involved in several pathophysiological processes that play a crucial role in the appearance of cardiovascular disease(CVD) or cancer. The aim of this review is to update the knowledge of the modulation of immune cell activation by different dietary patterns and its components focusing on CVD or cancer. While a westernized high-saturated fat highcarbohydrate diet is positively associated with lowgrade inflammation, vegetable- and fruit-based diets rich in monounsaturated fatty acids, polyunsaturated fatty acids and polyphenols, key nutrients of Mediterranean diet, decrease the levels of cellular and circulating inflammatory biomarkers thereby reducing the risk of related chronic diseases.

Stem and immune cells in colorectal primary tumour:Number and function of subsets may diagnose metastasis

An important percentage of colorectal cancer （CRC） patients will develop metastasis, mainly in the liver, even after a successful curative resection. This leads to a very high mortality rate if metastasis is not detected early on. Disseminated cancer cells develop from metastatic stem cells （MetSCs）. Recent knowledge has accumulated about these cells particularly in CRC, so they may now be tracked from the removed primary tumour. This approach could be especially important in prognosis of metastasis because it is becoming clear that metastasis does not particularly rely on testable driver mutations. Among the many traits supporting an epigenetic amplifcation of cell survival and self-renewal mechanisms of MetSCs, the role of many immune cell populations present in tumour tissues is becoming clear. The amount of tumour-infiltrating lymphocytes （T, B and natural killer cells）, dendritic cells and some regulatory populations have already shown prognostic value or to be correlated with disease-free survival time, mainly in immunohistochemistry studies of unique cell populations. Parallel analyses of these immune cell populations together with MetSCs in the primary tumour of patients, with later follow-up data of the patients, will define the usefulness of specific combinations of both immune and MetSCs cell populations. It is expected that these combinations, together to different biomarkers in the form of an immune score, may predict future tumour recurrences, metastases and/or mortality in CRC. It will also support the future design of improved immunotherapeutic approaches against metastasis.

Chitosan DNA nanoparticles for oral gene delivery

Gene therapy is a promising technology with potential applications in the treatment of medical conditions, both congenital and acquired. Despite its label as breakthrough technology for the 21st century, the simple concept of gene therapy - the introduction of a functional copy of desired genes in affected individuals - is proving to be more challenging than expected. Oral gene delivery has shown intriguing results and warrants further exploration. In particular, oral administration of chitosan DNA nano-particles, one the most commonly used formulations of therapeutic DNA, has repeatedly demonstrated successful in vitro and in vivo gene transfection. While oral gene therapy has shown immense promise as treatment options in a variety of diseases, there are still signifcant barriers to overcome before it can be considered for clinical applications. In this review we provide an over-view of the physiologic challenges facing the use of chitosan DNA nanoparticles for oral gene delivery at both the extracellular and intracellular level. From administration at the oral cavity, chitosan nanoparticles must traverse the gastrointestinal tract and protect its DNA contents from signifcant jumps in pH levels, various intestinal digestive enzymes, thick mucus layers with high turnover, and a proteinaceous glycocalyx meshwork. Once these extracellular barriers are overcome, chitosan DNA nanoparticles must enter intestinal cells, escape endolysosomes, and disassociate from genetic material at the appropriate time allowing transport of genetic material into the nucleus to deliver a therapeutic ef-fect. The properties of chitosan nanoparticles and modified nanoparticles are discussed in this review. An understanding of the barriers to oral gene delivery and how to overcome them would be invaluable for future gene therapy development.

GRP78 expression beyond cellular stress:A biomarker for tumor manipulation

Physiological stress takes place in the endoplasmicreticulum （ER） of cells where activation and up-regulationof genes and proteins are primarily induced to enhancepro-survival mechanisms such as the unfolded protein response （UPR）. A dominant protein in the UPR response is the heat shock GRP78 protein. Although GRP78 is primarily located in the ER, under certain conditions it is transported to the cell surface, where it acts as a receptor inducing pathways of cell signaling such as proliferation or apoptosis. In the prolonged chronic stress transportation of the GRP78 from the ER to the cell membrane is a major event where in addition to the presentation of the GRP78 as a receptor to various ligands, it also marks the cells that will proceed to apoptotic pathways. In the normal cell that under stress acquires cell surface GRP78 and in the tumor cell that already presents cell surface GRP78, cell surface GRP78 is an apoptotic fag. The internalization of GRP78 from the cell surface in normal cells by ligands such as peptides will enhance cell survival and alleviate cardiovascular ischemic diseases. The absence of cell surface GRP78 in the tumor cells portends proliferative and metastatic tumors. Pharmacological induction of cell surface GRP78 will induce the process of apoptosis and might be used as a therapeutic modality for cancer treatment.

Adenosine amine congener ameliorates cisplatin-induced hearing loss

AIM: To investigate a novel pharmacological intervention to mitigate cisplatin ototoxicity using a selective adenosine A1 receptor agonist adenosine amine congener(ADAC).METHODS: Male Wistar rats(8-10 wk) were exposed to a two-cycle cisplatin treatment similar to clinical course of cancer chemotherapy. Each cycle comprised 4 d of intraperitoneal cisplatin injections(1 mg/kg twice daily) separated by 10 d of rest. ADAC(100 μg/kg) or drug vehicle solution(control) was administered intraperitoneally for 5 d at 24 h intervals during the second cisplatin cycle(Regime 1), or upon completion of the cisplatin treatment(Regime 2). Hearing thresholds were measured using auditory brainstem responses(ABR) before cisplatin administration(baseline) and 7 d after the end of cisplatin treatment. Histological analysis of cochlear tissues included hair cell counting and qualitative assessment of apoptosis using terminal deoxynucleotidyl transferase mediated d UTP nick end labelling(TUNEL) staining.RESULTS: ABR threshold shifts in cisplatin-treated Wistar rats ranged from 5-29 d B across the frequency range used in the study(4-24 k Hz). Higher frequencies(16-24 k Hz) were mostly affected by cisplatin ototoxicity(mean threshold shift 25-29 d B). ADAC treatment during the second cisplatin cycle reduced cisplatininduced threshold shifts by 12-16 d B(P < 0.01) at higher frequencies compared to control vehicle-treated rats. However, the treatment was ineffective if ADAC administration was delayed until after the completion of the cisplatin regime. Functional recovery was supported by increased survival of hair cells in the cochlea. Qualitative analysis using TUNEL staining demonstrated reduced apoptosis of the outer hair cells and marginal cells in the stria vascularis in animals treated with ADAC during the second cisplatin cycle.CONCLUSION: A1 adenosine receptor agonist ADAC mitigates cisplatin-induced cochlear injury and hearing loss, however its potential interference with antineoplastic effects of cisplatin needs to be established.