细胞生物学治疗方法在椎间盘退行性病变方面的研究

在最近几年几种以细胞为基础的治疗来刺激椎间盘再生过程得到倡议：造血干细胞（ haematopoietic stem cells HSC ）、胎儿脊柱细胞（ fetal spine cells ）、永生性髓核细胞系（ immor-talized NP－cell lines ）、自体椎间盘软骨细胞（ autologous IVD chondrocytes ）、胚胎干细胞（ embryonic stem cells SC ），诱导性多能行胚胎干细胞（ induced pluripotent SC ）、嗅觉胚胎干细胞（ olfactory SC ）和来源于骨髓或脐带血的细胞的MSC已经被证明具有促进椎间盘再生／修复的潜力。髓核祖细胞（从髓核中单独分离得到的大约具有1％的比率）可分化为软骨形成细胞和神经源性细胞系，表明具有促进椎间盘再生的潜力［1］。除了椎间盘再生之外，祖细胞可能起到保护性作用。在调节椎间盘的炎症方面，在体外共同培养的纤维环细胞与巨噬细胞中研究发现家兔髓核祖细胞被证明可降低促炎性细胞：IL－6、IL－8以及iNOS的表达水平［99］。对于椎间盘再生而言，MSC为最主要的具有吸引力的替代细胞类型，部分是因为它们能够做为自体移植物。在犬类动物模型的研究中，MSCs能够增加Ⅱ型胶原的表达同时降低椎间盘内细胞凋亡的数量。在家兔模型中， MSCs能够在椎间盘中保持24周左右。但是移植性MSCs的数量最为关键。犬类动物模型中，每个椎间盘含有的MSCs细胞数量非常关键，每个椎间盘中会有106个MSCs最为理想，因为105个MSCs可导致细胞的生存能力下降，而107个MSCs可诱导细胞凋亡。除了MSCs的多种分化能力之外其与免疫调节相关的作用已经得到证明。 MSCs在炎症中的作用是建立在它们作为细胞因子释放工厂直接与损伤细胞相互作用的积极作用［2］。在一项小鼠的肺损伤模型中研究中，MSCs被发现可分泌IL－1Ra或在小鼠梗死模型中产生有能力的抗炎症蛋白：TNF－α刺激基因／蛋白6（ TNF－αstimulated gene／protein 6 TSG－6）。有趣的是在全身性应用MSCs之后，TSG－6也被鉴定为大鼠角膜损伤模型中的关键因子。将MSCs移植入小猪、兔、犬椎间盘后，在FaS配体（其他的免疫特免位点发现的一种蛋白质）表达重新恢复，表明MSCs可能分化为细胞表达FasL，也可能刺激新生的髓核细胞产生这种FasL，这样会促成在退变性椎间盘中免疫特免位点的恢复。

炎症性肠病生物学治疗的研究进展

IBD的发病机制是一个令人产生极大兴趣的谜团。近年来,由于IBD的发病机制正在不断地阐明和更好地认识,促进了针对某些特定靶分子的新生物学治疗方法的开发并取得了较大的进展。目前业已明确的是有几种介质至关重要地参与诱导和维持粘膜的炎症,将这些介质的每一个分子作为靶标,均能代表一种合理的和特异的干预治疗策略。

PVM方案加康莱特治疗非小细胞肺癌

ＰＶＭ方案加康莱特治疗非小细胞肺癌赵龙妹，李玉升，李峻岭，屈凤莲，崔成旭，储大同中国医学科学院，中国协和医科大学，肿瘤医院生物化疗科（北京１０００２１）非小细胞肺癌（ＮＳＣＬＣ）的治疗应首选手术，对Ⅲ、Ⅳ期病人来说，则应考虑以全身治疗为主的综合治疗。...

细胞因子诱导的杀伤细胞在肿瘤治疗中的研究和临床应用现状

肿瘤免疫学治疗的目的是激发或调动机体的免疫系统,增强肿瘤微环境抗肿瘤免疫力,从而控制和杀伤肿瘤细胞。肿瘤免疫学治疗的方法种类繁多,已与现代生物高科技技术结合,发展成为继手术、化疗和放疗之后的第4种肿瘤治疗模式——肿瘤生物学治疗方法。

试析原发性肝癌的生物学基础

从生物学方面研究肝癌的病因和发生机制,可为肝癌的临床治疗及健康预防,找寻确切生物学依据和开辟新的治疗方法。DNA多倍体肝癌的恶性程度高于DNA二倍体肝癌,相应的预后差于DNA二倍体肝癌。肝癌的发生与癌基因、抑癌基因的表达及HBV感染均有关系,癌基因的异常表达及HBV感染促成癌细胞的生成和生长。基于以上认识,在试行产生了免疫治疗、肿瘤基因治疗和RNA干扰技术等新的肝癌生物治疗方法。

努力探索椎间盘退变的生物学治疗方法

分子生物学、细胞生物学和组织工程学等学科的迅速发展，为骨科疾病的治疗提供了新的手段，进而开辟了新的领域。新的手段主要包括以细胞学为基础的组织移植或自身细胞的基因修饰等，最终达到生物学修复的目的。目前上述技术已应用于多种组织。

Biofeedback therapy for dyssynergic defecation

Dyssynergic defecation is one of the most common forms of functional constipation both in children and adults; it is defined by incomplete evacuation of fecal material from the rectum due to paradoxical contraction or failure to relax pelvic floor muscles when straining to defecate. This is believed to be a behavioral disorder because there.are no associated morphological or neurological abnormalities, and consequently biofeedback training has been recommended for treatment. Biofeedback involves the use of pressure measurements or averaged electromyographic activity within the anal canal to teach patients how to relax pelvic floor muscles when straining to defecate. This is often combined with teaching the patient more appropriate techniques for straining （increasing intra-abdominal pressure） and having the patient practice defecating a water filled balloon. Tn adults, randomized controlled trials show that this form of biofeedback is more effective than laxatives, general muscle relaxation exercises （described as sham biofeedback）, and drugs to relax skeletal muscles. Moreover, its effectiveness is specific to patients who have dyssynergic defecation and not slow transit constipation. However, in children, no clear superiority for biofeedback compared to laxatives has been demonstrated. Based on three randomized controlled studies in the last two years, biofeedback appears to be the preferred treatment for dyssynergic defecation in adults.

Comparative analysis of intestinal microbial community diversity between healthy and orally infected ducklings with Salmonella enteritidis by ERIC-PCR

AIM: To analyze the difference of intestinal microbial community diversity between healthy and (S. enteritidis) orally infected ducklings.METHODS: Enterobacterial Repetitive Intergenic Consensus (ERIC)-PCR was applied to analyze the intestinal microbial community diversity and dynamic change including duodenum, jejunum, ileum, cecum and rectum from healthy ducklings and 7-day-old ducklings after oral infection with S. enteritidis at different time points.RESULTS: The intestinal microbial community of the control healthy ducklings was steady and the ERIC-PCR band numbers of the control healthy ducklings were the least with rectum and were the most with caecum. ERIC-PCR bands of orally inoculated ducklings did not obviously change until 24 h after inoculation (p.i.). The numbers of the ERIC-PCR bands gradually decreased from 24 h to 72 h p.i., and then, with the development of disease, the band numbers gradually increased until 6 d p.i. The prominent bacteria changed because of S. enteritidis infection and the DNAstar of staple of ERIC-PCR showed that aerobe and facultative aerobe (Escherichia coli, Shigella, Salmonella) became preponderant bacilli in the intestine of orally infected ducklings with SE.CONCLUSION: This study has provided significant data to clarify the intestinal microbial community diversity and dynamic change of healthy and S. enteritidis orally infected ducklings, and valuable insight into the pathogenesis of S. enteritidis infection in both human and animals.

Stem cells for end stage liver disease: How far have we got?

End stage liver disease (ESLD) is a health problem worldwide. Liver transplantation is currently the only effective therapy, but its many drawbacks include a shortage of donors, operative damage, risk of rejection and in some cases recidivism of the pre-transplant disease. These factors account for the recent growing interest in regenerative medicine. Experiments have sought to identify an optimal source of stem cells, sufficient to generate large amounts of hepatocytes to be used in bioartificial livers or injected in vivo to repair the diseased organ. This update aims to give non-stem cell specialists an overview of the results obtained to date in this fascinating field of biomedical research.

Biomarkers in chronic kidney disease,from kidney function to kidney damage

Chronic kidney disease(CKD) typically evolves over many years, with a long latent period when the disease is clinically silent and therefore diagnosis, evaluation and treatment is based mainly on biomarkers that assess kidney function. Glomerular filtration rate(GFR) remains the ideal marker of kidney function. Unfortunately measuring GFR is time consuming and therefore GFR is usually estimated from equations that take into account endogenous filtration markers like serum creatinine(SCr) and cystatin C(Cys C). Other biomarkers such as albuminuria may precede kidney function decline and have demonstrated to have strong associationswith disease progression and outcomes. New potential biomarkers have arisen with the promise of detecting kidney damage prior to the currently used markers. The aim of this review is to discuss the utility of the GFR estimating equations and biomarkers in CKD and the different clinical settings where these should be applied. The CKD-Epidemiology Collaboration equation performs better than the modification of diet in renal disease equation, especially at GFR above 60 m L/min per 1.73 m2. Equations combining Cys C and SCr perform better than the equations using either Cys C or SCr alone and are recommended in situations where CKD needs to be confirmed. Combining creatinine, Cys C and urine albumin to creatinine ratio improves risk stratification for kidney disease progression and mortality. Kidney injury molecule and neutrophil gelatinase-associated lipocalin are considered reasonable biomarkers in urine and plasma to determine severity and prognosis of CKD.

The human leucocyte differentiation antigens (HLDA) workshops: the evolv-ing role of antibodies in research, diagnosis and therapy

The 8^th International Workshop on Human Leucocyte Differentiation Antigens （chaired by HZ and managed by BS） was run over a 4-year period and culminated in a conference in December 2004. Here we review the achievements of the HLDA Workshops and provide links to information on CD molecules and antibodies against them, including the 93 new CDs assigned in the 8^th Workshop. We consider what remains to be achieved （including an estimate of the number of leucocyte surface molecules still to be discovered）, and how the field can best move forward.

A ruptured large extraluminal ileal gastrointestinal stromal tumor causing hemoperitoneum

We describe an 87-year-old woman with a large ileal gastrointestinal stromal tumor (GIST) causing hemoperitoneum. A CT scan demonstrated a large heterogeneous mass measuring about 13 cm × 11 cm in the pelvis and hemoperitoneum, with a non-uniform enhancement pattern. The mass was diagnosed as a GIST originating from the gastrointestinal tract. She underwent an urgent laparotomy and an ileal GIST with a rupture was found 130 cm from the anal to the Treitz’s ligament. Hemoperitoneum caused by ileal GIST rupture is a rare condition. Bleeding in the large tumor leading to rupture of the capsule might cause hemoperitoneum in the present case.

Neurotrophic and metabotrophic potential of nerve growth factor and brain-derived neurotrophic factor: Linking cardiometabolic and neuropsychiatric diseases

One of biggest recent achievements of neurobiology is the study on neurotrophic factors. The neurotrophins are exciting examples of these factors. They belong to a family of proteins consisting of nerve growth fac-tor （NGF）, brain-derived neurotrophic factor （BDNF）, neurotrophin-3 （NT-3）, NT-4/5, NT-6, and NT-7. Today, NGF and BDNF are well recognized to mediate a diz-zying number of trophobiological effects, ranging from neurotrophic through immunotrophic and epitheliotro-phic to metabotrophic effects. These are implicated in the pathogenesis of various diseases. In the same vein, recent studies in adipobiology reveal that this tissue is the body’s largest endocrine and paracrine organ producing multiple signaling proteins collectively termed adipokines, with NGF and BDNF being also produced from adipose tissue. Altogether, neurobio-logy and adipobiology contribute to the improvement of our knowledge on diseases beyond obesity such as cardiometabolic （atherosclerosis, type 2 diabetes, and metabolic syndrome） and neuropsychiatric （e.g. , Alzheimer’s disease and depression） diseases. The present review updates evidence for （1） neurotrophic and metabotrophic potentials of NGF and BDNF linking the pathogenesis of these diseases, and （2） NGF- and BDNF-mediated effects in ampakines, NMDA receptor antagonists, antidepressants, selective deacetylase inhibitors, statins, peroxisome proliferator-activated receptor gamma agonists, and purinergic P2X3 recep-tor up-regulation. This may help to construct a novel paradigm in the feld of translational pharmacology of neuro-metabotrophins, particularly NGF and BDNF.

Antimicrobial resistance in clinically important biofilms

A biofilm contains a consortium of cohesive bacterial cells forming a complex structure that is a sedentary, but dynamic, community. Biofilms adhere on biotic and abiotic surfaces, including the surfaces of practically all medical devices. Biofilms are reported to be responsible for approximately 60% of nosocomial infections due to implanted medical devices, such as intravenous catheters, and they also cause other foreign-body infections and chronic infections. The presence of biofilm on a medical device may result in the infection of surrounding tissues and failure of the device, necessitating the removal and replacement ofthe device. Bacteria from biofilms formed on medical devices may be released and disperse, with the potential for the formation of new biofilms in other locations and the development of a systemic infection. Regardless of their location, bacteria in biofilms are tolerant of the activities of the immune system, antimicrobial agents, and antiseptics. Concentrations of antimicrobial agents sufficient to eradicate planktonic cells have no effect on the same microorganism in a biofilm. Depending on the microbial consortium or component of the biofilm that is involved, various combinations of factors have been suggested to explain the recalcitrant nature of biofilms toward killing by antibiotics. In this mini-review, some of the factors contributing to antimicrobial resistance in biofilms are discussed.

Drug-transporter interaction testing in drug discovery and development

The human body consists of several physiological barriers that express a number of membrane transporters. For an orally absorbed drug the intestinal, hepatic, renal and blood-brain barriers are of the greatest importance. The ATP-binding cassette(ABC) transporters that mediate cellular efflux and the solute carrier transporters that mostly mediate cellular uptake are the two superfamilies responsible for membrane transport of vast majority of drugs and drug metabolites. The total number of human transporters in the two superfamilies exceeds 400, and about 40-50 transporters have been characterized for drug transport. The latest Food and Drug Administration guidance focuses on P-glycoprotein, breast cancer resistance protein, organic anion transporting polypeptide 1B1(OATP1B1), OATP1B3, organic cation transporter 2(OCT2), and organic anion transporters 1(OAT1) and OAT3. The European Medicines Agency's shortlist additionally contains the bile salt export pump, OCT1, and the multidrug and toxin extrusion transporters, multidrug and toxin ex-trusion protein 1(MATE1) and MATE2/MATE2 K. A variety of transporter assays are available to test drugtransporter interactions, transporter-mediated drugdrug interactions, and transporter-mediated toxicity. The drug binding site of ABC transporters is accessible from the cytoplasm or the inner leaflet of the plasma membrane. Therefore, vesicular transport assays utilizing inside-out vesicles are commonly used assays, where the directionality of transport results in drugs being transported into the vesicle. Monolayer assays utilizing polarized cells expressing efflux transporters are the test systems suggested by regulatory agencies. However, in some monolayers, uptake transporters must be coexpressed with efflux transporters to assure detectable transport of low passive permeability drugs. For uptake transporters mediating cellular drug uptake, utilization of stable transfectants have been suggested. In vivo animal models complete the testing battery. Some issues, such as in vivo relevance, gender difference, age and ontogeny issues can only be addressed using in vivo models. Transporter specificity is provided by using knock-out or mutant models. Alternatively, chemical knock-outs can be employed. Compensatory changes are less likely when using chemical knockouts. On the other hand, specific inhibitors for some uptake transporters are not available, limiting the options to genetic knock-outs.

Therapeutic effect of different treatment methods on functional anorectal pain

Objective： To observe the clinical efficacy of oral traditional Chinese medicine （Jiaweitiaoqi decoction）, electroacupuncture, biofeedback, and combined treatment on functional anorectal pain （FAP）. Methods： A total of 200 patients with FAP were randomly divided into 4 groups, with 50 patients in each group. Group 1 was given oral Jiaweitiaoqi decoction; group 2 was given electroacupuncture at the lumbosacral acupoints; group 3 was given biofeedback training; and group 4 was given combined treatment. The numeric rating scale （NRS）, Short Form-36 （SF-36） quality of life scale, static pressure of the anal canal, and maximum systolic pressure were observed in the 4 groups. Results： The observation indices of the 4 groups were all improved after treatment compared with those before treatment, and the fourth group showed the most obvious improvement. Regarding NRS scores, the static pressure of the anal canal, and maximum systolic pressure, group 4 had lower values than the other 3 groups （P 〈 0.05 for all）. In the SF-36 quality of life score, group 4 showed a higher value than the other 3 groups （P 〈 0.05）. Conclusion： Non-drug therapy including acupuncture and physical exercise can enhance the clinical efficacy of single Chinese medicine in the treatment of FAP .

Measurement of Tip Trajectories in the Cardiac Reentry

Reentrant impulse in the myocardium is considered to be a major factor promoting electrophysiological abnormalities or even leading to ventricular tachycardias (VTs) and ventricular fibrillations (VFs). Tip trajectory of the reentrant wave can reflect stability of the electrical propagation and area of the reentrant movement, thereby being considered as one of the most concerned parameters in studying electrical activities during VT/VF. The purpose of the present study is to propose a practical method to find out tip trajectories using a computational approach. In this study Luo-Rudy 1991 mathematical model of the ventricular cell was used. The operator splitting method was utilized to integrate the partial differential equations in the two-dimensional tissue. And spiral waves were initiated by the cut wave front technique. Through experiments we found it was difficult to find out the tips by finding intersection of the two isovoltage lines as proposed in most papers. Therefore, we suggested that tip points were detected by seeking the shortest distance of the two adjacent isovoltage contour lines. The results showed that tip trajectories of these spiral waves found in our way were very near to the tips observed, implying validation of our method in measuring tip trajectories in cardiac reentry.

Healed and Crippled： The Effect of Global Medicine on African Indigenous Treatment and Care Approaches

Whereas global medicine and health care practices have improved the quality of people＇s lives, especially in the developing countries data abounds that local communities have been crippled by the same medical practises. Some societies in developing countries have become sources of specimen for clinical trials of biomedicine which is unaffordable to their citizens. This paper explores the neglect of traditional African medicinal innovations and research in favour of imported Western medicine perpetuated by the developed countries. The paper argues that global medicine and health care have neither utilized nor recognized the African Traditional Medicine （ATM） fully, despite the fact that cultures in developed world used and continue to utilize the indigenous medical knowledge. The paper further argues that instead of neglecting African Traditional Medicine, ATM and biomedicine can be more beneficial by blending them into a single system, through what we would call in this paper High-Performance Medical Research （HPMR）. This would allow participation of communities to achieve both socio-eeonomic and medical knowledge growth rather than being a monopoly and preserve of developed organizations in the North. This paper proposes that HPMR should be a systematic and scientific approach for enhancing local people＇s participation in the development of medical ventures. This paper draws on secondary data on traditional African therapeutic practices by some local communities in East Africa combined with literature review on medical practice in Western societies.