Statins and intracerebral hemorrhage

Objective To briefly review the literature regarding the impact of statins on the prevention and treatment of stroke,especially on intracerebral hemorrhage （ICH）.We described statins＇ effects,mechanism of ICH,serum total cholesterol and ICH,and the relationship between statins and ICH.Data sources All articles used in this review were mainly searched from the PubMed database with no limitations of language and year of publication.Study selection Randomized controlled studies,prospective cohort studies,animal experiments,and meta-analysis articles related to this topic in the past decade were selected.Results Statins play an important role in the primary and secondary prevention of cardiovascular diseases and also have an impact on the treatment of vascular diseases.There still exist controversies about the relationship between statins and ICH.More clinical and experimental trials indicate that statins do not increase the risk of ICH.Conclusion A low or a regular dose of statins would not increase the risk of ICH.     

Issues about the nocebo phenomena in clinics

During clinical work, some side-effects may occur to patients, part of which are caused by the specific pharrnacological effects of drugs and some of which are non-specific. Although these phenomena happen from time to time, burdening the anguish and expenditure of patients, their nature is still less understood. Recently, as the research of the placebo effect become deeper and deeper, clinicians and researchers have gradually realized that mind plays an important role in the occurrence of non-specific side-effects, which is called ＂nocebo effect＂ professionally, the evil side of placebo effect. This article would expatiate on nocebo effect in detail from several aspects, such as its mechanism, effect, influencing factors and discuss how to make it known and treated in clinical practice and clinical trials.     

What ＂helps＂ tumors evade vascular targeting treatment？

Objective To throw a light on the possible factors which might induce resistance of vascular targeting treatment in tumors by reviewing the recent publications in the field of tumor angiogenesis and vascular targeting treatment. Data sources The data used in this review were mainly from Medline and PubMed for relevant English language articles published from 1971 to January 2008. The search terms were ＂angiogenesis＂, ＂ascular targeting treatment＂ and ＂endothelial progenitor cells＂. Study selection Articles involved in the possible influence factors during angiogenesis and vascular targeting treatment were selected, including angiogenic or anti-angiogenic mechanism, tumor vasculature, tumor cells, cancer stem cells and endothelial progenitor cells. Results As a promising strategy vascular targeting treatment still has experimental and clinical setbacks which may term tumor vasculature＇s resistance to anti-angiogenesis agents. There are several possible explanations for such a resistance that might account for clinical and preclinical failures of anti-angiogenic treatment against tumor. Proangiogenic effect of hypoxia, normal tumor vasculature, escape of tumor cells and tumor vasculogenesis are included. This review reveals some clues which might be helpful to direct future research in order to remove obstacles to vascular targeting treatment. Conclusions Generally and undoubtedly vascular targeting treatment remains a promising strategy. But we still have to realize the existence of a challenging future. Further research is required to enhance our knowledge of vascular targeting treatment strategy before it could make a more substantial success.     

乙型病毒性肝炎相关失代偿肝硬化的抗病毒治疗进展

Objective: To review the development, mechanism, necessity and limitation of antiviral therapy in decompensated hepatitis B virus-related cirrhosis. Data sources: A literature search (Pubmed 2000 to 2011) was performed using the key words “antiviral and decompensated hepatitis B virus-related cirrhosis” mainly. Relevant book chapters were also reviewed. Study selection: Well-controlled, prospective landmark studies and review articles on antiviral therapy in decompesated hepatitis B virus-related cirrhosis were selected. Results: Specific antiviral agents which not only control viral replication, therefore permitting liver transplantation, but also improve liver function so significantly that patients could be removed from the transplant waiting list. However, the emergence of drug-resistant mutants can result in treatment failure. Combination therapy is a save-strategy in drug-resistant. Conclusions: Although the treatment of end-stage liver disease is still a challenge in worldwide, antiviral therapy has altered the natural history of hepatitis B virus patients with decompensated cirrhosis. The approval of the new generation of antivirals is opening new perspectives for finding the optimal antiviral treatment for patients with decompensated cirrhosis and preventing antiviral resistance. A combination of antivirals may be one of the future strategies for fulfilling these goals.     

Renal denervation: a new therapeutic approach for resistant hypertension

Objective To review the advances in studies on renal denervation. Data sources References concerning renal denervation and resistant hypertension cited in this review were collected from PubMed published in English and those of renal denervation devices from official websites of device manufacturers up to January 2014. Study selection Articles with keywords ＂renal denervation＂ and ＂resistant hypertension＂ were selected. Results Renal and systemic sympathetic overactivity plays an important role in pathology of hypertension as well as other diseases characterized by sympathetic overactivity. Renal denervation is a new, catheter based procedure to reduce renal and systemic sympathetic overactivity by disruption of renal sympathetic efferent and afferent nerves through radiofrequency or ultrasound energy delivered to the endoluminal surface of both renal arteries. Although several studies have shown the efficacy and safety of renal denervation in the treatment of resistant hypertension and the potential benefit of the procedure in other diseases, Symplicity HTN 3 study, the most rigorous clinical trial of renal denervation to date, failed to meet its primary endpoint. The procedure also has other limitations such as the lack of long term, efficacy and safety data and the lack of the predictors for the blood pressure lowering response and nonresponse to the procedure. An overview of current renal denervation devices holding Conformite Europ6enne mark is also included in this review. Conclusions Renal denervation is a promising therapeutic approach in the management of resistant hypertension and other diseases characterized by sympathetic overactivity. In its early stage of clinical application, the efficacy of the procedure is still controversial. Large scale, blind, randomized, controlled clinical trials are still necessary to address the limitations of the procedure.     

Current advances in diagnostic methods of Acanthamoeba keratitis

Objective The objective of this article was to review the current advances in diagnostic methods for Acanthamoeba keratitis （AK）.Data sources Data used in this review were retrieved from PubMed （1970-2013）.The terms ＂Acanthamoeba keratitis＂ and ＂diagnosis＂ were used for the literature search.Study selection Data from published articles regarding AK and diagnosis in clinical trials were identified and reviewed.Results The diagnostic methods for the eight species implicated in AK were reviewed.Among all diagnostic procedures,corneal scraping and smear examination was an essential diagnostic method.Polymerase chain reaction was the most sensitive and accurate detection method.Culturing of Acanthamoeba was a reliable method for final diagnosis of AK.Confocal microscopy to detect Acanthamoeba was also effective,without any invasive procedure,and was helpful in the early diagnosis of AK.Conclusion Clinically,conjunction of various diagnostic methods to diagnose AK was necessary.     

Current state of clinical diagnosis and treatment of infantile cytomegaloviral hepatitis

<正>Cytomegaloviral hepatitis is an infantile liver disease commonly encountered in China,which could be differentiated into 4 patterns with different clinical conditions.Along with the progress of laboratory diagnostic techniques,multiple diagnostic approaches are available for this disease,but accurate diagnosis can only be made when individual patients' realities are taken into consideration.Clinical treatments are various, and the Western medicine used is mainly anti-viral agents such as Ganciclovir,and so far no unified therapeutic program has been formed.More and more ways of regarding Chinese medicine treatment of cytomegaloviral hepatitis have been published increasingly in recent years,though further research to seek preferable treatment programs is still expected.     

Pig islets for islet xenotransplantation: current status and future perspectives

Objective To review the current status and progress on pig islet xenotransplantation.Data sources Data used in this review were mainly from English literature of Pubmed database.The search terms were ＂pig islet＂ and ＂xenotransplantation＂.Study selection The original articles and critical reviews selected were relevant to this review＇s theme.Results Pigs are suggested to be an ideal candidate for obtaining available islet cells for transplantation.However,the potential clinical application of pig islet is still facing challenges including inadequate yield of high-quality functional islets and xenorejection of the transplants.The former can be overcome mainly by selection of a suitable pathogen-free source herd and the development of isolation and purification technology.While the feasibility of successful preclinical pig islet xenotranplantation provides insights in the possible mechanisms of xenogeneic immune recognition and rejection to overwhelm the latter.In addition,the achievement of long-term insulin independence in diabetic models by means of distinct islet products and novel immunotherapeutic strategies is promising.Conclusions Pig islet xenotransplantation is one of the prospective treatments to bridge the gap between the needs of transplantation in patients with diabetes and available islet cells.Nonetheless,further studies and efforts are needed to translate obtained findings into tangible applications.     

Mechanism of Avastin in Treatment of Cancer： A Review

Angiogenesis is one of the key acquired characteristics or ＂hallmarks＂ essential for the growth and development of all tumor types. The anti-angiogenic agent Avastin has demonstrated clinical efficacy in a range of different tumor types, regardless of tumor or patient characteristics. Clinical trials have reported that Avastin can be combined safely and effectively with both chemotherapy and immunotherapy. This review examines the three main effects of Avastin on tumor vasculature： regression, normalization and inhibition, and how these translate into clinical efficacy. This review further explores the clinical benefits of incorporating Avastin into anticancer treatment strategies, including a discussion of which patients are likely to benefit from therapy and which agents can be combined with Avastin.     

Selection of allografts for impaction bone grafting for bone defect reconstruction on the acetabular side

Objective To review the choices of allografts for bone defect reconstruction in acetabular revision surgery using the technique of impaction bone grafting.Data sources The data cited in this review were mainly obtained from articles listed in PubMed that were published from January 1993 to July 2009. The search terms were ＂impaction bone grafting＂, ＂particle size＂, ＂mechanical property＂and ＂biological behavior＂.Study selection Articles relevant to the choices of allografts and their results for bone defect reconstruction on the acetabular side were selected.Results Different choices of allografts, including the particle size, process of irradiation or fat reduction, composition and particle grade, are made to improve the survival rate of a prosthesis in acetabular revision surgery. This review,which compares both mechanical and biological factors, summarizes the experimental and clinical results for different techniques.Conclusions Fresh frozen cancellous allografts with particle sizes ranging from 7 to 10 mm are a favorable choice for reconstruction of bone defects of American Academy of Orthopedic Surgeons （AAOS） types Ⅱ （cavitary defect） and Ⅲ（combined cavitary and segmental defect） on the acetabular side. A fat-reducing procedure with saline or solvent/detergent is controversial. Adding autologous marrow into irradiated allografts, which provides reliable mechanical stability and biological safety, may be a substitute for fresh frozen allografts. Cortical bone can be a supplementary material in cases of insufficiency of cancellous allografts. Cartilage should be excluded from the graft material. Further research is required to demonstrate the best particle grade, and randomized controlled trials in clinical practice are required to obtain more information about the selection of allografts.     

Progress of anti-vascular endothelial growth factor therapy for ocular neovascular disease: benefits and challenges

publication. Study selection Clinical trials and case studies presented at medical conferences and published in peer-reviewed literature in the past decade were reviewed. Results Anti-VEGF agents have manifested great potential and promising outcomes in treating ocular neovascularization, though some of them are still used as off-label drugs. Intravitrea~ injection of anti-VEGF agents could be accompanied by devastating ocular or systemic complications, and intimate monitoring in both adult and pediatric population are warranted. Future directions should be focused on carrying out more well-designed large-scale controlled trials, promoting sustained duration of action, developing safer and more efficient generation of anti-VEGF agents. Conclusions Anti-VEGF treatment has proved to be beneficial in treating both anterior and posterior neovascular ocular diseases. However, more safer and affordable antiangiogenic agencies and regimens are warranted to be explored.     

Helicobacter pylori infection: an overview in 2013, focus on therapy

Objective This article aimed to review the incidence of Helicobacterpylori （H.pylon） infection and its therapy.Data sources Relevant articles published in English were identified by searching in PubMed from 2000 to 2013,with keywords ＂H.pylori＂.Important references from selected articles were also retrieved from Elsevier,Wiley,EBSCO,and SPRINGER.The Chinese articles published were searched from China National Knowledge Infrastructure （CNKI）.Study selection Articles about ＂prevalence＂,＂gastric carcinoma＂,＂peptic ulcer＂,＂gastroesophageal reflux disease＂,＂functional dyspepsia＂,＂pathogenic mechanism＂,＂therapy＂,＂eradication rate＂,＂antibiotic resistance＂,and ＂gene polymorphisms＂ were selected.Results The decreased infection rates of H.pylori could also be linked to the changed disease spectrum,such as the decreased morbidity and recurrence rate of H.pylori-related peptic ulcer,and the increased morbidity of gastroesophageal reflux.Although different treatment regimens have been used for H.pylori infection,the H.pylori eradication rate declined gradually.Due to primary resistance to antibiotics,the gene polymorphism of host and infected strain,and the therapy regimes,H.pylori eradication became even more difficult.Conclusions The prevalence of H.py/ori infection had been decreasing,but the rate of eradication failure has dramatically risen in many countries due to resistance to antibiotic.H.pylori therapy in clinical practice is becoming proqressively more difficult.     

Aspirin and esophageal squamous cell carcinoma: bedside to bench

Objective To review the advances of studies on clinical results of aspirin＇s chemopreventive effect against esophageal squamous cell carcinoma （ESCC） and evidences for mechanisms of the antitumoural effects of aspirin in experimental research.Data sources A comprehensive search of the PubMed literatures without restriction on the publication date was carried out using keywords such as aspirin and esophageal cancer.Study selection Articles associated with aspirin and esophageal cancer are analyzed.Results This review focuses on the current evidence for use of aspirin as a chemopreventive agent in ESCC.Aspirin is the most widely used among all nonsteroidal anti-inflammatory drugs （NSAIDs）,which is cheap and acceptable to patients.Several observational results provide the further investigation of prevention and therapy of aspirin or similar drugs in esophageal cancer.Data from case control studies,cohort studies and randomized controlled trials （RCTs） also give some support of a beneficial role of aspirin on ESCC.Experimental data suggest that aspirin may prevent carcinogenesis of ESCC by favorably affecting proliferation,apoptosis,or other as yet unidentified growth-regulating processes.But the mechanism by which aspirin influence on esophageal squamous cell carcinoma needs further investigation.Conclusion A wealth of evidences ranging from clinical data to experimental results are building to suggest that aspirin has significant effects in reducing both the incidence and mortality of ESCC.     

DC-SIGN: binding receptors for hepatitis C virus

Objective To review the recent developments in and research into binding receptors of hepatitis C virus (HCV) and especially the role of dendritic cell-specitic adhesion receptor (DC-SIGN) in HCV. Data sources Both Chinese- and English-languge literature was searched using MEDLINE (2000-2003) and the databank of Chinese-language literature (2000-2003). Study selection Relevant articles on DC-SIGN and HCV binding receptors in recent domestic and foreign literature were selected.Data extraction Data were mainly extracted from 40 articles which are listed in the references section of this review. Results DC-SIGN, a dendritic cell-specific adhesion receptor and a type Ⅱ transmembrane mannose-binding C-type lectin, is very important in the function of dendritic cells (DC), both in mediating naive T cell interactions through ICAM-3 and as a rolling receptor that mediates the DC-specific ICAM-2-dependent migration processes. It can be used by HCV and other viral and bacterial pathogens including human immunodeficiency virus (HIV), Ebola virus, CMV and Mycobacterium tuberculosis to facilitate infection. Both DC-SIGN and DC-SIGNR can act either in cis, by concentrating virus on target cells, or in trans, by transmission of bound virus to a target cell expressing appropriate entry receptors. Recent report showed that DC-SIGN not only plays a role in entry into DC, HCV E2 interaction with DC-SIGN might also be detrimental to the interaction of DC with T cells during antigen presentation. Conclusions DC-SIGNs are high-affinity binding receptors for HCV. The clinical strategies that target DC-SIGN may be successful in restricting HCV dissemination and pathogenesis as well as directing the migration of DCs to manipulate appropriate immune responses in autoimmunity and tumorigenic situations.     

Association between clinical features and prognosis of patients with limb-shaking transient ischemic attack

Objective This review aims to illustrate the relationship between clinical features and the prognosis of patients with limb-shaking transient ischemic attack （LS-TIA）. Data sources Relevant articles published in two main Chinese medical periodical databases （China National Knowledge Infrastructure and China Science Periodical Database） from 1986 to June 2013 were identified with keywords ＂limb shaking＂ and ＂transient ischemic attack＂. Study selection Original articles and case reports about LS-TIA were selected. Results A total of 63 cases collected from 19 articles were included in the pooled analysis. Ls-rlA presented in two cerebrovascular diseases, of which atherosclerotic high-grade stenosis or occlusion in carotid artery system and moyamoya disease formed 95.2% and 4.8%, respectively. Of 63 patients, 11 （17.5%） were once misdiagnosed as epileptic and prescribed useless antiepilepsy drugs. The multivariable Logistic regression model showed a significant protective effect of patients with revascularization therapy on prognosis, compared with patients treated with drugs （odds ratio 0.20, 95% CI 0.05-0.74, P=0.016）. Conclusions Chronic carotid artery system hypoperfusion can induce limb（s） shaking, followed by high possibility of ischemic stroke in the same brain territorial. Revascularization of the responsible artery may work better than conservative drug-based therapy.     

Thymoma: current diagnosis and treatment

Objective To review the presentation,diagnosis,staging and treatment of thymoma.Data sources Data were obtained from papers on thymoma published in English within the last 30 years.No formal systematic...     

Issues on the selection of non-inferiority margin in clinical trials

Objective The determination of non-inferiority margin is an important and confusing issue which directly influences the acceptability of a new medication. We reviewed the published literature, International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use （ICH） Guidelines and Committee for Proprietary Medicinal Products （CPMP） papers on the selection of non-inferiority margin and the corresponding statistical tests in clinical trials, in order to provide practical recommendations and suggestions for establishing reference criteria for the non-inferiority margin in China.
Data sources The literature on the selection of a non-inferiority margin and statistical tests was mainly extracted from relevant English articles on non-inferior clinical trials published from 1990 to 2007. The starting point （1990） was chosen due to lack of such papers published prior to 1990. This literature was searched via PubMed, Medline and Chinese Knowledge Information （CNKI）. ICH guidelines and CPMP papers were downloaded from their official websites. The keywords ＂clinical trial＂, ＂non-inferiority＂ and ＂non-inferiority margin＂ were used.
Study selection Forty-three original articles and critical reviews, ICH El0 guideline and CPMP papers were selected. Results The non-inferiority testing with treatment difference and ratio are commonly used, where the non-inferiority margin is determined with and without historical data. Traditionally, this margin is treated as a fixed value, while developed methods take the variation into account in the determination of this margin, on which the test depends is more convincing. The mixed margin consisting of a margin based on treatment difference and a margin based on treatment ratio can exactly control the type I error at the desirable level and obtain a better power. In this review, we also provide some recommendations and suggestions for the selection of the non-inferiority margin in the western countries and China.
Conclusions Besides the magnitude and variability of the standard control and placebo effects, the determination of the margin depends on other factors, such as, the safety profiles of the two comparative therapies, method of administration and product cost. Hence the margin should be made specifically for a certain case. Reference criteria for different medications should be given to avoid the arbitrary conclusion.     

Endostatin derivative angiogenesis inhibitors

Objective To throw light on the superiority of the anti-angiogenesis activity of endostatin （ES） derivatives by reviewing the recent progress in the field of ES molecular structure modification. Data sources The data used in this article were mainly from PubMed with relevant English articles published from 1971 to May 2008. The search terms were ＂endostatin＂ and ＂angiothesis＂. Study selection Articles involved in the ES molecular structure modification and the original milestone articles were selected. Results A number of ES derivatives were designed and studied to improve its clinical relevance. The modified ES with polyethylene glycol （PEG）, low molecular weight heparin （LMWH） and IgG Fc domain extended the circulation half-life. Meanwhile the recombinant ESs showed more potent anti-tumor activity than native ES in mouse xenografts. Mutated ES also changed its anti-angiogenesis activity. Conclusions The anti-angiogenesis treatment remains a promising tumor therapeutic strategy. New ES derivatives would be a good choice to meet the future challenge on clinical application of ES.     

Unexpected positive cultures including isolation of Propionibacterium acnes in revision shoulder arthroplasty

Objective Little information is available to guide treatment strategies regarding patients with unexpected positive cultures （UPC）,including Propionibacterium acnes （PA）,without overt signs of infection in revision shoulder arthroplasty （RSA）.The purpose of our study was to analyze the prevalence,clinical meaning,treatment and prognosis of UPC in RSA.Data sources and study selection We performed a systematic review of the literature between 1950 and 2013 for all studies reporting on UPC for PA.Studies with the prevalence and prognosis of patients with UPC in RSA were analyzed.Results Six studies meeting our inclusion criteria yielded data for 1 402 patients who underwent a total of 1405 RSA.Based on the available data,following RSA 235 shoulders had UPCs with a pooled percentage of 16.7％ （235/1405）.The most commonly isolated bacteria from shoulders following RSA with UPCs was PA with pooled percentages of 63.4％ （149/235）.Occurrence of true infection from UPCs after RSA was seen in 24 shoulders （24/235,10.2％）.Antibiotic use did not influence the rate of the occurrence of true infection from UPCs （P=0.498）.Conclusions Our study showed a low risk of having a true infection from UPCs after RSA without clinical signs of preoperative infection at the time of the surgery.Therefore,prolonged antibiotic therapy may not be necessary in these patients.