Recent trends in the surgical management of inflammatory bowel disease

Surgery is required in the vast majority of patients with Crohn’s disease (CD) and in approximately one-third of patients with ulcerative colitis (UC). Similar to medical treatments for IBD, significant advances have occurred in surgery. Advances in CD include an emphasis upon conservatism as exemplified by more limited resections, strictureplasties, and laparoscopic resections. The use of probiotics in selected patients has improved the outcome in patients with pouchitis following restorative proctocolectomy for UC. It is anticipated that ongoing discoveries in the molecular basis of IBD will in turn identify those patients who will best respond to surgery.

Amelioration of collagen-induced arthritis by CD95 (Apo-1/Fas)-ligand gene transfer

Both rheumatoid arthritis and animal models ofautoimmune arthritis are characterized by hyper-activation of synovial cells and hyperplasia of the synovialmembrane. The activated synovial cells produceinflammatory cytokines and degradative enzymes whichlead to destruction of cartilage and bones. Effectivetreatment of arthritis may require elimination of most orall activated synovial cells. The death factor

Quick to remember, slow to forget： rapid recall responses of memory CD8^＋ T cells

The functional roles of memory B and T lymphocytes underlie the phenomenal success of prophylactic vaccinations, which have decreased morbidities and mortalities from infectious diseases globally over the last 50 years. However, it is becoming increasingly appreciated that memory cells are also capable of mediating the pathology associated with autoimmune disorders and transplant rejection, and may pose a significant barrier to future clinical advancement in immunoregulation. Therefore, understanding the unique properties of memory lymphocytes （as compared to their naive precursors） is a major area of investigation. Here, we focus on one of those singular properties of memory T cells （TM）-rapid recall. As will be discussed in more detail, rapid recall refers to the ability of quiescent TM cells to efficiently and robustly express‘effector functions＇ following stimulation. Studies that have advanced our understanding of TM cells＇ rapid recall using CD4^＋ T cells have been expertly reviewed elsewhere, so we will focus primarily on studies of CD8^＋ T cells. We will first review the different ways that CD8^＋ TM cells can be generated, followed by discussing how this influences their functional properties in the settings of immune protection and pathology. Then, rapid recall ability will be discussed, with emphasis placed on what is currently known about the mechanisms that underlie this unique property of TM cells.

Time Course of Age-dependent Changes in Intraocular Pressure and Retinal Ganglion Cell Death in DBA/2J Mouse

Purpose:To characterizes the progression of glaucoma in DBA/2J mice by measuring intraocular pressure(IOP) and retinal ganglion cells(RGCs) numbers in mice of various ages. Methods:A quantitative assessment of the pathophysiology of the DBA/2J mice was performed and the C57/BL6 mice was used as control. The IOP was measured by the servo-null micropipette system; the regional patterns of the loss of RGCs were determined by cell count of retrogradely-labeled RGCs. Results:The baseline IOP for DBA/2J mice at 7 weeks was (16.6 ± 1.2)mm Hg.Then IOP increased extend to 12 months, with the peak of (25.2 ± 1.2)mm Hg at 6 months of age. Retinal ganglion cell numbers did not decrease relative to control until 12 months of age(P=0.006), when the loss was proportionally higher in peripheral regions(P<0.05). Conclusion:The elevation in IOP precedes the loss of RGCs by several months. RGCs cell loss occurs particularly in peripheral regions of the retina. These findings expand our understanding of the changes in DBA/2J mice and provide information for experiments design when they are used as a glaucoma model for future studies of RGCs degeneration in glaucoma.

Regional disease characteristics and comorbidities of patients with schizophrenia in the Ziprasidone Observational Study of Cardiac Outcomes (ZODIAC): Findings from an international large simple trial

Background: Using baseline data from the Ziprasidone Observational Study of Cardiac Outcomes (ZODIAC), we assessed disease characteristics and prevalence of select comorbidities among subjects with schizophrenia in different clinical settings across 18 countries. ZODIAC was a randomized, open-label, one-year, large simple trial (LST) that enrolled 18,239 individuals with schizophrenia. Methods: Subjects were randomized to open-label treatment with ziprasidone (n = 9120) or olanzapine (n = 9119) in naturalistic (usual care) settings and followed for one year. Study sites (n = 749) applied minimal selection criteria in an attempt to make the study population as representative as possible of those receiving treatment in “real world” circumstances across the countries. Results: Mean patient age was 41 years, 55% were male, 34% were markedly ill or presented with more severe disease, and 66% of subjects had one or more select comorbid conditions [i.e. heart attack, stroke, hypertension, CAD/angina, high cholesterol/triglycerides, diabetes, or overweight (BMI ≥ 25)] at baseline. History of suicide attempt was greatest in the US (38%), compared with Sweden (34%), Brazil/South America (26%), Asia (23%), and Eastern Europe (20%). Overweight or obesity was the most prevalent comorbid risk factor, representing 60% of enrolled subjects, 70% of US subjects compared with 30% in Asia and 52% - 64% in the other regions studied. High cholesterol/triglycerides levels were found in 23% of US subjects compared with a relatively low prevalence in other countries (3% - 11%). History of cardiovascular or diabetes-related comorbidities was found in 31% of subjects. Current smoking (46.5%) and past smoking (11.8%) were common with men dominating the proportion of current smokers: US (61%);Asia (60%);Sweden (50%);Eastern Europe (49%);and Latin America (44%). Conclusions: Our findings indicate substantial baseline variations across countries in demographics, comorbid conditions, and psychiatric disease history. These data provide an international epidemiologic picture of schizophrenia and may help guide future research and treatment initiatives.

Evidence for the involvement of ActA in maturation of the Listeria monocytogenes phagosome

Dear Editor, Listeria monocytogenes （Lm）, a Gram-positive facultative bacterium, is the causative agent of listeriosis, a food-borne disease affecting humans. During infections, Lm enters phagosomes from which it escapes into the cytoplasm. Listeriolysin O （LLO） is essential, and two phospholipases play a role in this process. Actin polymerization provides the propulsive force that moves the bacteria through the cytoplasm and into adjacent cells. It is initiated by the interaction of the N-terminal domain of ActA,

Summary overview of human gene therapy trials in the U.S.

It has been approximately six and one-half yearssince the first patient was enrolled in a gene therapyclinical trial. Since that important begining, this typeof genetic intervention has grown into a worldwideinvestigative activity involving about 2100 patients asof December 1996. Although it was initially

Peripheral clonal deletion of MBP-specific T cells by intravenous au-toantigen: rapid reversal of ongoing, progressive experimental autoimmune encephalomyelitis

Experimental autoimmune encephalomyelitis can be initiated spontaneously and developed progressively in TCR transgenic mice specific for myelin basic protein when exposed to non-sterile environment, thus more closely mimicking human multiple sclerosis. By intravenous administration of myelin basic protein, we succeeded in rapidly reversing the clinical and pathological signs of progressive spontaneous disease in these mice. The majority of transgenic T cells of MBP-injected mice was deleted, with dramatically increased numbers of apoptotic cells, in lymph nodes and spleen, but not in thymus. Proliferative responses of

Regulation of the subcellular localization of TRAF2 by TRAF1 reveals mechanisms of TRAF2 signaling

TRAF2 is a critical adaptor molecule for TNF receptors in inflammatory and immune signaling. Upon receptor engagement, TRAF2 is recruited to CD40 and translocates to lipid rafts in a RING finger-dependent process, which enables the activation of downstream kinases. TRAF1 can displace TRAF2 and CD40 from raft fractions, and it promotes the ability of TRAF2 to sustain signal activation. Replacement of the RING finger of TRAF2 with a raft-targeting signal restores JNK activation and association with the cytoskeletal protein Filamin, but not NF-KB activation. TRAF1-/-dendritic cells show attenuated

Specifically Binding of L-ficolin to N-glycans of HCV Envelope Glycoproteins E1 and E2 Leads to Complement Activation

L-ficolin, one of lectin families, is a recently identified complement factor that initiates lectin pathway of complement. Little is known about its role in viral hepatitis. In the present study, we found that L-ficolin in serum from 103 patients with hepatitis C virus （HCV）, were significantly higher than that in 150 healthy controls. We further found that L-ficolin expressions were significantly increased in vitro study by HCV JFH-1 infected human hepatocyte cell line Huh7.5.1. Investigation of the mechanisms of the L-ficolin action on HCV demonstrated that L-ficolin protein could recognize and bind to envelope glycoproteins E1 and E2 of HCV, activating the lectin complement pathway-mediated cytolytic activity in HCV-infected hepatocyte. This interaction between L-ficolin and HCV E1 and E2 glycoproteins was attributed to the N-glycans of E1 and E2. These findings provide new insights into the biological functions of L-ficolin in clinically important hepatic viral diseases.

Papillary thyroid cancer and inflammatory bowel disease:Is there a relationship?

AIM:To formally study age of diagnosis of papillary thyroid cancer(PTC) in inflammatory bowel disease(IBD) patients and evaluate the prevalence of PTC in IBD patients compared to a control population.pothesis that patients with IBD are more likely to be diagnosed with PTC than a control population.A retrospective cohort analysis was performed using the University of Pennsylvania Health System's electronic database.Outpatients from 1998-2009 were included in the search,and patients in the cohort were selected based on ICD-9 codes.Inclusion criteria included the diagnosis of Crohn's disease(CD) or ulcerative colitis(UC) and the concurrent diagnosis of thyroid cancer in comparison to a control population.Using these methods 912 patients with CD and 1774 with UC were compared to 1638 diverticulitis and 19 447 asthma controls.Statistics were performed using corrected chisquare analysis.The primary outcome for this study was the diagnosis of PTC.Approval to conduct this study was obtained by the Institutional Review Board at the University of Pennsylvania.RESULTS:The mean age was 47.5 years(range:18-102 years) and 66% patients were female.An analysis of variance model was used to compare the age of PTC diagnosis between the CD,UC,asthma and diverticulitis groups,and a statistically significant difference in age at PTC diagnosis was noted across all groups(F = 6.35,df = 3,P = 0.0006).The age of PTC diagnosis in CD patients was statistically significantly lower than UC,asthma,and diverticulitis patients(average PTC diagnosis age for CD 25,UC 49,asthma 45,diverticulitis 63).After covarying for sex and age in 2009,the difference in age at PTC diagnosis remained statistically significant(F = 4.13,df = 3,P = 0.0089).A total of 86 patients were diagnosed with PTC.Nine patients(0.5%) with UC were diagnosed with PTC.Patients with UC were not shown to be more likely to develop PTC [odds ratio(OR):1.544,95%CI 0.767-3.108] compared to asthma controls.Four patients(0.4%) with CD were diagnosed with PTC.Patients with CD were not shown to be more likely to develop PTC(OR:1.334,95%CI 0.485-3.672) compared to a control population with asthma.Nine patients(0.5%) with a history of diverticulitis were diagnosed with PTC.Patients with diverticulitis were not shown to be more likely to develop PTC(OR:1.673,95%CI 0.831-3.368) compared to asthma controls.Patients with CD or UC were not less likely to develop PTC compared to those with diverticulitis(CD OR:0.80,95%CI 0.25-2.60;UC OR:0.92,95%CI 0.37-2.33).None of the patients used immunosuppressant medications prior to the diagnosis of PTC(azathioprine,6-mercaptopurine,and methotrexate).CONCLUSION:There is a significant difference in age of diagnosis of PTC in patients with CD compared to patients with UC and the control populations studied.

Portable ultrasonography in mass casualty incidents:The CAVEAT examination

Ultrasonography used by practicing clinicians has been shown to be of utility in the evaluation of time-sensitive and critical illnesses in a range of environments,including pre-hospital triage,emergency department,and critical care settings.The increasing availability of lightweight,robust,user-friendly,and low-cost portable ultrasound equipment is particularly suited for use in the physically and temporally challenging environment of a multiple casualty incident(MCI).Currently established ultrasound applications used to identify potentially lethal thoracic or abdominal conditions offer a base upon which rapid,focused protocols using hand-carried emergency ultrasonography could be developed.Following a detailed review of the current use of portable ultrasonography in military and civilian MCI settings,we propose a protocol for sonographic evaluation of the chest,abdomen,vena cava,and extremities for acute triage.The protocol is two-tiered,based on the urgency and technical difficulty of the sonographic examination.In addition to utilization of well-established bedside abdominal and thoracic sonography applications,this protocol incorporates extremity assessment for long-bone fractures.Studies of the proposed protocol will need to be conducted to determine its utility in simulated and actual MCI settings.

INTRINSIC FLUORESCENCE CHANGES IN NERVE TERMINALS,EVOKED BY ACTION POTENTIALS,ARE MODULATED BY KREBS CYCLE SUBSTRATES

Electrical stimulation of the mammalian neurohypophysial infundibular stalk evokes the entry of Nat and Ca^(2+) into the neurosecretory terminals during the action potential.These events,in turn,increase intracellular Ca^(2+) and activate NaK-and Ca-ATPases,prompting the mitochondria to increase oxidative phosphorylation which can be monitored by recording the changes in FAD and NADHfluorescence.This paper reflects our efforts to determine whether or not modulating the capacity of mitochondria to produce ATP,by changing the concentrations of two important substrates of the Krebs cycle of the nerve terminal mitochondria,pyruvate and glucose,has an effect on the intrinsicfluorescence changes triggered by action potential stimulation.

IMAGING REDOX STATE HETEROGENEITY WITHIN INDIVIDUAL EMBRYONIC STEM CELL COLONIES

Redox state mediates embryonic stem cell(ESC)differentiation and thus offers an important complementary approach to understanding the pluripotency of stem cells.NADH redox ratio(NADH/(Fp t NADH)),where NADH is the reduced form of nicotinamide adenine dinucleotide and Fp is the oxidizedflavoproteins,has been established as a sensitive indicator of mitochondrial redox state.In this paper,we report our redox imaging data on the mitochondrial redox state of mouse ESC(mESC)colonies and the implications thereof.The low-temperature NADH/Fp redox scanner was employed to image mESC colonies grown on a feeder layer of gamma-irradiated mouse embryonicfibroblasts(MEFs)on glass cover slips.The result showed significant heterogeneity in the mitochondrial redox state within individual mESC colonies(size:~200-440μm),exhibiting a core with a more reduced state than the periphery.This more reduced state positively correlates with the expression pattern of Oct4,a well-established marker of pluripotency.Our observation is thefirst to show the heterogeneity in the mitochondrial redox state within a mESC colony,suggesting that mitochondrial redox state should be further investigated as a potential new biomarker for the stemness of embryonic stem cells.

标准化眼眶回波描记检查证实的疑难性眼部失调患者存在隐匿性甲状腺相关眼病

Purpose:To describe the clinical presentation,orbital echography(OE)findings,and neuroimaging results of patients with chronic unexplained ocular misalignment,which includes patients with clinically occult thyroid eye disease(TED)that is identifiable through a characteristic OE appearance.Design:Retrospective observational case series.Methods:Seventy eight patients with chronic ocular misalignment suspected of TED because of a history of systemic thyroid disease,proptosis,dysmotility,positive forced ductions,or eyelid retraction or lag were categorized as TED positive,negative,and indeterminate with the use of standardized OE.Demographic,clinical,OE,computed tomography,and magnetic resonance imaging information was collected.Analyses determined the prevalence of TED and differences between TED positive,negative,and indeterminate groups.Results:Fifty-five percent of the findings were suspicious for and most consistent with TED(TED positive);26% of the findings were TED negative,and 19% of the findings were TED indeterminate.Of 30 patients with newly diagnosed TED by OE,70% had no lid retraction,and 20% had no other findings of TED.The inferior rectus followed by the superior rectus/levator complex,medial rectus,and lateral rectus muscles were the most frequently involved muscles.Neuroimaging that was performed in only 26 of 78 patients(33%)did not appear to yield additional diagnostic information.Conclusion:TED is a potential cause of chronic unexplained ocular misalignment in a substantial proportion of patients.These patients frequently present in an occult fashion without other clinical findings that are typical of TED.In these patients,a diagnosis of TED by OE can reduce further costly evaluation.OE appears to have significant clinical usefulness in the diagnosis of TED in patients with unexplained ocular misalignment.

全身放疗及应用免疫抑制剂后发生多发性汗腺汗孔瘤

Eccrine poromas are benign, adnexal tumors that most often occur as a solitary lesion on the palm or sole. The occurrence of multiple eccrine poromas is extremely rare. In this report, we describe the development of several eccrine poromas in an acral distribution in a 42-year-old man. Before the appearance of these tumors, the patient had received total body irradiation and allogeneic bone marrow transplantation for treatment of acute lymphocytic leukemia. As a complication of the bone marrow transplant, the patient developed chronic graft-versus-host disease, which was treated with immunosuppressive therapy. We discuss this patient and review the available literature regarding multiple eccrine poromas.

家族性巨大平滑肌瘤和食管平滑肌瘤病:一位父亲和2个女儿不同寻常的临床表现

Esophageal leiomyomatosis and leiomyoma are benign neoplastic lesions composed of proliferating smooth muscle cells. Although rare, these 2 conditions may occur simultaneously in an individual patient. Symptomatic patients often require surgical management. We describe the first reported cases of family members presenting with esophageal leiomyomatosis and concomitant massive esophageal leiomyoma.

武汉市美沙酮门诊治疗者丙型肝炎病毒基因分型

目的探讨武汉市美沙酮门诊治疗者丙型肝炎病毒(HCV)及不同基因型感染状况。方法用酶标记免疫(ELISA)法检测抗-HCV抗体,在86份抗-HCV抗体阳性的血清标本中,分别提取HCV RNA,通过逆转录巢式聚合酶链反应(RT-nested PCR)扩增C基因的羧基至E1基因的氨基端长度为474 bp的片段,测定其核苷酸序列,与GenBank中已知的HCV序列进行系谱分析,确定HCV基因型。结果武汉市美沙酮门诊332名治疗者中抗-HCV IgG阳性率为94.3%;其中86份血清的HCV序列通过系谱显示6a型71例,占82.5%;3b 7例,占8.2%;1a 5例,占5.8%;1b 3例,占3.5%。结论武汉市美沙酮门诊入组的吸毒者HCV感染以6a型为优势株,其次为3b,吸毒者中HCV感染率较高,且基因亚型呈现多样性。

机器人辅助手术在头颈肿瘤外科中的应用进展

近年,机器人辅助手术(robot-assisted surgery,RAS)发展迅速,已成为外科学领域的研究热点之一。与传统手术相比,RAS在微创、美观和功能保存等方面具有明显优势,已逐步应用于神经外科、泌尿外科和头颈外科等领域的临床治疗。在头颈肿瘤的治疗中,RAS可有效降低手术损伤,加快患者术后恢复。本文就RAS在头颈肿瘤原发病灶的切除、颈淋巴结清扫术以及组织缺损修复重建三方面的应用作一综述。