王福生:乙型肝炎的生物治疗法

记者：王教授，您好!对于很多人来说，生物治疗是个陌生而又熟悉的词汇。有时候能从其他地方听到，但是具体是怎么样的却又不明白。您能先给我我们介绍下生物治疗的含义么？ 王福生：生物治疗其实是个很广泛的概念，它涉及一切应用生物大分子进行治疗的方法，比如抗体治疗、免疫治疗、细胞因子治疗等都属于生物治疗的范畴。

子宫内膜异位症药物及生物治疗新进展

子宫内膜异位症(endom etriosis,EMS)是妇科常见病,发病率呈上升趋势,传统药物及手术治疗方案存在副作用大及较高复发率等缺陷。随着对病因学的深入研究和分子生物学等相关学科的快速发展,抗粘附、抗血管生成、抗炎症、免疫调节剂和激素受体调节剂等"源头治疗"已成为研究热点,为EMS治疗提供了全新的对策。现对此研究的最新进展作一综述。

摩拉联合扩血管药物治疗突发性耳聋的临床观察

目的探讨摩拉联合扩血管药物治疗突发性耳聋的疗效。方法选取2013年10月~2016年10月120例(128耳)突发性耳聋患者为研究对象,将所有患者按入院时间随机分为两组,A组患者60例(66耳)给予摩拉治疗以及改善微循环、糖皮质激素及营养神经等综合治疗12 d;B组患者60例(62耳)单纯给予改善微循环、糖皮质激素及营养神经等综合治疗12 d。观察两组治疗情况。结果 A组的治疗总有效率为90.91%,高于B组的74.19%,经比较且差异具有统计学意义(P<0.05)。结论摩拉联合扩血管药物治疗突发性耳聋,能够显著提高临床疗效,且无毒副作用,值得应用推广。

生物刺激反馈治疗法联合盆底肌肉锻炼治疗女性盆底功能障碍性疾病的疗效评价

目的评价生物刺激反馈治疗法联合盆底肌肉锻炼治疗女性盆底功能障碍性疾病(PFD)的疗效。方法选择2014年7月1日-2016年7月1日喀什地区第一人民医院妇科门诊经筛查诊断为PFD并接受治疗的患者220例,随机分为治疗组和对照组,治疗组采用生物刺激反馈治疗法联合盆底肌肉锻炼治疗,对照组单纯采用Kegel训练(缩肛运动)治疗。1个疗程后进行一般情况问卷、调查压力性、尿失禁(SUI)改善情况、性生活情况及盆底肌肉功能评估,盆底器官脱垂(POP)测定等并评价治疗效果。结果盆底肌力恢复观察组有效率(97.14%),高于对照组(56.07%),差异有统计学意义;子宫脱垂(CPP)、性生活(SD)、压力性尿失禁(SUI)及下腹及阴道坠痛(POP)等方面两组均有不同程度改善,但观察组明显优于对照组,差异有统计学意义(χ2=11.457、14.265、17.257、22.019,均P<0.05)。结论生物刺激反馈治疗法联合盆底肌肉锻炼治疗PFD疗效满意且优于单纯盆底肌肉锻炼,该疗法能明显提高患者生活质量,具有无损伤、安全、有效、经济、方便的特点,值得临床应用和推广。

电疗联合生物反馈法对产后女性盆底功能障碍恢复的疗效观察

目的:观察分析产后女性盆底功能障碍患者采用电疗联合生物反馈法治疗的疗效。方法:选取本院收治的100例产后盆底功能障碍患者并参照数字随机方法将其分为参照组(n=50,予以传统盆底功能锻炼治疗)、研究组(n=50,在参照组基础上予以电疗联合生物反馈治疗法治疗),对比治疗前后两组患者的盆底肌力情况及压力性尿失禁与性生活质量的改善效果。结果:治疗后两组患者的盆底肌力均得到明显改善,研究组情况明显优于参照组(P<0.05);治疗后,研究组患者的压力性尿失禁的治疗有效率与性生活质量的好转率均明显优于参照组(P<0.05)。结论:产后女性盆底功能障碍患者采用电疗联合生物反馈治疗法进行治疗,能有效改善患者盆底肌力、压力性尿失禁与性生活质量情况。

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.

Innovative therapeutics for inflammatory bowel disease

Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the gastrointestinal tract, which clinically present as one of two disorders, Crohn's disease or ulcerative colitis. Mainstays of drug treatments for IBD include aminosalicylates, corticosteroids and immunosuppressants such as azathioprine, methotrexate and cyclosporin. Advances in basic research of the pathophysiological process in IBD have been applied to generate a variety of new therapeutics targeting at different levels of the inflammatory processes. New therapies are classified as: (1) Anti-TNFα antibodies; (2) Recombinant cytokines; (3) Selective adhesion blockade; (4) Growth factors; (5) Innate immunostimulation; (6) Nucleic acid based therapies; (7) Gene therapy; (8) Autologous bone-marrow transplantation; (9) Helminths and (10) Extracorporeal immunomodulation. All treatments have the potential to provide more effective and safe treatment for IBD.

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.

Metastatic colorectal cancer-past,progress and future

The clinical management of metastatic （stage IV） colorectal cancer （CRC） is a common challenge faced by surgeons and physicians. The last decade has seen exciting developments in the management of CRC, with significant improvements in prognosis for patients diagnosed with stage IV disease. Treatment options have expanded from 5-fluorouracil alone to a range of pharmaceutical and interventional therapies, improving survival, and providing a cure in selected cases. Enhanced understanding of the biologic pathways most important in colorectal carcinogenesis has led to a new generation of drugs showing promise in advanced disease. It is hoped that in the near future the treatment paradigm of metastatic CRC will be analogous to that of a chronic illness, rather than a rapidly terminal condition. This overview discusses the epidemiology of advanced CRC and currently available therapeutic options including medical, surgical, ablative and novel modalities in the management of metastatic colorectal cancer.

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.

Getting the right stuff: controlling neural stem cell state and fate in vivo and in vitro with biomaterials

Stem cell therapy holds great promises in medical treatment by, e.g., replacing lost cells, re-constitute healthy cell populations and also in the use of stem cells as vehicles for factor and gene delivery. Embryonic stem cells have rightfully attracted a large interest due to their proven capacity of differentiating into any cell type in the embryo in vivo. Tissue-specific stem ceils are however already in use in medical practice, and recently the first systematic medical trials involving human neural stem cell （NSC） therapy have been launched. There are yet many obstacles to overcome and procedures to improve. To ensure progress in the medical use of stem cells increased basic knowledge of the molecular mechanisms that govern stem cell characteristics is necessary. Here we provide a review of the literature on NSCs in various aspects of cell therapy, with the main focus on the potential of using biomaterials to control NSC characteristics, differentiation, and delivery. We summarize results from studies on the characteristics of endogenous and transplanted NSCs in rodent models of neurological and cancer diseases, and highlight recent advancements in polymer compatibility and applicability in regulating NSC state and fate. We suggest that the development of specially designed polymers, such as hydrogels, is a crucial issue to improve the outcome of stem cell therapy in the central nervous system.

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.

Role of conventional therapies in the era of biological treatment in Crohn’s disease

Outstanding progress regarding the pathophysiology of Crohn's disease (CD) has led to the development of innovative therapeutic concepts. Numerous controlled trials have been performed in CD. This review concentrates on the results of randomized,placebo-controlled trials,and meta-analyses when available,that provide the highest degree of evidence. Current guidelines on the management of CD recommend a step-up approach to treatment involving the addition of more powerful therapies as the severity of disease and refractoriness to therapy increase. The advent of biological drugs has opened new therapeutic horizons for treating CD,modifying the treatment goals. However,the large majority of patients with CD will be managed through conventional therapy,even if they are a prelude to biological therapy.

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.

Biological effect of expression of exogenous human nuclear receptor hLRH-1 in SW480 cells and its molecular mechanism

Objective： To explore the possible biological function of human nuclear receptor hLRH-1 in tumorigenesis and progress of colon cancer. Methods： Plasmids pcDNA3-hLRH-1 were introduced into SW480 cells via lipofectamine. The expression of mRNA and protein of exogenous hLRH-1 were detected by RT-PCR and western blotting, respectively. MTT assay was carried out to survey the proliferation of SW480 cells with overexpression of hLRH-1. Meanwhile, the expression of proliferation-related genes cyclin E1 and cyclin D1, and apoptosis-related genes PTEN and Rbl, were analyzed by realtime RT-PCR. Results： The proliferation of SW480 cells was promoted under the condition of overexpression of hLRH-1. The expression of cyclin E1 was up-regulated significantly, while that of PTEN and Rbl were down-regulated in SW480 cells with overexpressed hLRH-1. Conclusion： The expression of exogenous hLRH-1 in SW480 cells induced the proliferation resulting form up-regulation of cyclin E1, as well as participated in the regulation of apoptosis via influencing the expression of PTEN and Rb1.