糖尿病患者足溃疡减压指南(2023年更新版)——《国际糖尿病足工作组:糖尿病相关的足病预防与管理指南(2023)》的一部分

减轻组织的机械性压力在治愈糖尿病相关的足溃疡所需的多种干预措施中最为重要。本文是2023年国际糖尿病足工作组(IWGDF)发布的减压治疗促进糖尿病相关的足溃疡愈合的循证指南,也是对2019年IWGDF指南的更新。我们遵循推荐、评估、发展和评价分级(GRADE)方法学,以患者-干预-比较-结局(patient-intervention-control-outcome,PICO)模式设计临床问题和重要结果,进行系统评价和Meta分析,制定评判表汇总,为每个问题编写推荐和理由。每项推荐都是基于系统综述中发现的证据,在无证据情况下则采用专家意见,以及对判断项目的GRADE等级总结进行仔细权衡,包括可预期和不可预期的影响、证据的确定性、患者价值、所需资源、成本效益、公平性、可行性和可接受性。为了治愈糖尿病患者神经性前足底或中足底溃疡,要使用不可拆卸的齐膝高减压装置作为首选减压干预措施。如果患者存在对不可拆卸减压装置的禁忌证或不能耐受,考虑使用可拆卸齐膝(或踝)高减压装置作为减压干预措施的第二选择。如果无可用的减压装置,考虑使用合适的鞋具结合毡制泡沫作为减压干预措施的第三选择。如果这种非手术减压治疗不能治愈前足底溃疡,可以考虑跟腱延长术、跖骨头切除术、关节置换术或跖骨截骨术。为了治疗继发于屈趾畸形的神经性足底或小趾远端溃疡,可行趾屈肌腱切开术。为了促进后足、非足底或并发感染或缺血的溃疡的愈合,提出了进一步的推荐。所有推荐都已在减压临床路径中进行了总结,以帮助促进本指南在临床实践中的实施。这些减压推荐将帮助医务人员为糖尿病相关的足溃疡患者提供最佳的治疗和预后,降低患者感染、住院和截肢的风险。

Fecal microbiota transplantation for the treatment of irritable bowel syndrome:A systematic review and meta-analysis

BACKGROUND Irritable bowel syndrome(IBS)is the most prevalent gastrointestinal disorder in developed countries and reduces patients’quality of life,hinders their ability to work,and increases health care costs.A growing number of trials have demonstrated an aberrant gut microbiota composition in IBS,also known as‘gut dysbiosis’.Fecal microbiota transplantation(FMT)has been suggested as a treatment for IBS.AIM To assess the efficacy and safety of FMT for the treatment of IBS.METHODS We searched Cochrane Central,MEDLINE,EMBASE and Web of Science up to 24 October 2022 for randomised controlled trials(RCTs)investigating the effectiveness of FMT compared to placebo(including autologous FMT)in treating IBS.The primary outcome was the number of patients with improvements of symptoms measured using a validated,global IBS symptoms score.Secondary outcomes were changes in quality-of-life scores,non-serious and serious adverse events.Risk ratios(RR)and corresponding 95%CI were calculated for dichotomous outcomes,as were the mean differences(MD)and 95%CI for continuous outcomes.The Cochrane risk of bias tool was used to assess the quality of the trials.GRADE criteria were used to assess the overall quality of the evidence.RESULTS Eight RCTs(484 participants)were included in the review.FMT resulted in no significant benefit in IBS symptoms three months after treatment compared to placebo(RR 1.19,95%CI:0.68-2.10).Adverse events were reported in 97 participants in the FMT group and in 45 participants in the placebo group(RR 1.17,95%CI:0.63-2.15).One serious adverse event occurred in the FMT group and two in the placebo group(RR 0.42,95%CI:0.07-2.60).Endoscopic FMT delivery resulted in a significant improvement in symptoms,while capsules did not.FMT did not improve the quality of life of IBS patients but,instead,appeared to reduce it,albeit non significantly(MD-6.30,95%CI:-13.39-0.79).The overall quality of the evidence was low due to moderate-high inconsistency,the small number of patients in the studies,and imprecision.CONCLUSION We found insufficient evidence to support or refute the use of FMT for IBS.Larger trials are needed.

Retinal pigment epithelium–Bruch’s membrane volume in grading of age-related macular degeneration

AIM:To assess the agreement of optical coherence tomography(OCT)algorithm-based retinal pigment epithelium–Bruch’s membrane complex volume(RBV)with fundus photograph-based age-related macular degeneration(AMD)grading.METHODS:Digital color fundus photographs(CFPs)and spectral domain OCT images were acquired from 96 elderly subjects.CFPs were graded according to Age-Related Eye Disease Study(AREDS)classification.OCT image segmentation and RBV data calculation were done with OrionTM software.Univariate and multivariate analyses were performed to find out whether AMD lesion features associated with higher RBVs.RESULTS:RBV correlated with AMD grading(rs=0.338,P=0.001),the correlation was slightly stronger in early AMD(n=52;rs=0.432,P=0.001).RBV was higher in subjects with early AMD compared with those with no AMD lesions evident in fundus photographs(1.05±0.20 vs 0.96±0.13 mm3,P=0.023).In multivariate analysis higher RBVs were associated significantly with higher total drusen(β=0.388,P=0.027)and pigmentation areas(β=0.319,P=0.020)in fundus photographs,whereas depigmentation area(β=-0.295,P=0.015)associated with lower RBV.CONCLUSION:RBV correlate with AMD grading status,with a stronger association in patients with moderate,non-late AMD grades.This effect is driven mostly by lesions with drusen or pigmentation.Lesions with depigmentation tend to have lower values.RBV is more comprehensive measurement of the key area of AMD pathogenesis,compared to sole drusen volume analysis.RBV measurements are independent on grader variations and offer a possibility to quantify early and middle grade AMD lesions in a research setting,but may not substitute fundus photograph-based grading in the whole range of AMD spectrum.

Clinico-Epidemiological Characteristics and Survival Outcomes of COVID-19 Infection in Kassala, Eastern Sudan

Introduction: Severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) represents a major health problem worldwide. Thus, early detection and appropriate management of the virus will influence the outcome of the disease. This study aimed to investigate the epidemiological characteristics and survival outcomes of patients with COVID-19 infection in Kassala, Eastern Sudan. Methods: A cross-sectional hospital-study was conducted among patients visiting Kassala teaching hospital with suspicion of COVID-19 infection. A structured questionnaire was used to gather clinical and socio-demo- graphic information from COVID-19 patients. Nasopharyngeal specimens and blood samples were collected and tested to confirm the diagnosis of COVID-19 infection using RT-PCR. Results: A total of 371 patients were enrolled in the study from September 2020 to January 2021, with mean age ± SD was 42.9 ± 19.9. The prevalence of COVID-19 infection was estimated at 61.7%. The majority were males 159 (69.4%), of university-level education, 96 (49.7%), and urban residents, 175 (9.7%). The most common symptoms were fever 215 (93.9%), cough 188 (82.1%), headache 179 (78.2%), and shortness of breath 154 (67.2%). Overall all mortality was reported as 16%. Older age group with the age ≥ 70, P P = 0.020, diabetes mellitus P = 0.029 were significantly associated with high case fatality. Conclusion: This study demonstrated that older age, male gender, laboratory tests (leukocytosis, lymphopenia, low Hemoglobin and high CRP) and various comorbid conditions significantly increase the disease severity and mortality. Therefore, attention should be paid to preventive measures to reduce the considerable impacts of the disease.

土壤中全氟和多氟烷基化合物的污染现状及环境行为

全氟和多氟烷基化合物(perfluoroalkyl and polyfluoroalkyl substances,PFASs)是一类新兴持久性有机污染物.土壤中PFASs可以通过淋溶作用进入地下水影响水质安全,或者通过陆生食物链的传递和生物放大作用危害生态系统和人类健康,有关土壤中PFASs的赋存状况、浓度水平与行为机制的研究已经成为环境化学领域的热点之一.目前土壤中可以准确测定的PFASs在含氟化合物总量中的占比不到1%,含量为ng g水平.我国相关研究主要集中在东部及氟化工厂周边地区,其组分以全氟辛烷磺酸(Perfluorooctane sulfonic acid,PFOS)和全氟辛酸(Perfluorooctanoic acid,PFOA)等长链PFASs为主.不同类型土壤中PFASs的赋存特征主要受到物质种类与土壤理化性质及周边人类活动的影响.除了含氟化学品生产和使用过程中的直接释放和大气传输以外,PFASs前体物在土壤环境中的转化也是其重要来源.吸附-解吸是PFASs在土壤中的主要归趋方式,化合物碳链长度及官能团种类、土壤理化性质和生物种类等因素都会影响其在土壤中的迁移转化和富集能力.鉴于目前的研究现状,需要进一步优化土壤中PFASs的提取和分析方法,关注新型PFASs在土壤中的变化趋势及行为机制,开展土壤中PFASs的生物可给性和生物可利用性研究,进一步评估PFASs的生态与人体健康风险.

睾酮对人体骨骼肌作用的细胞与分子机制:非法提高竞技能力的背后

睾酮是种促同化激素,在一些特殊群体包括一些职业运动员、业余运动员、学龄期儿童以及那些单纯为了改变外形的人群中的使用并不陌生.睾酮,因其能增强肌肉的强度,提高肌肉含量而受到药物滥用者的热烈欢迎.药物滥用者非法使用睾酮及其相关类固醇药物以提高肌力并且增加肌肉质量从而提高其竞技成绩,这对其他竞技者而言有失公平.……

Colorectal cancer in patients with inflammatory bowel disease:Can we predict risk?

The inflammatory bowel diseases(IBD),Crohn's disease(CD) and ulcerative colitis(UC),may be complicated by colorectal cancer(CRC).In a recent populationbased cohort study of 47 347 Danish patients with IBD by Tine Jess and colleagues 268 patients with UC and 70 patients with CD developed CRC during 30 years of observation.The overall risk of CRC among patients with UC and CD was comparable with that of the general population.However,patients diagnosed with UC during childhood or as adolescents,patients with long duration of disease and those with concomitant primary sclerosing cholangitis were at increased risk.In this commentary,we discuss the mechanisms underlying carcinogenesis in IBD and current investigations of genetic susceptibility in IBD patients.Further advances will depend on the cooperative work by epidemiologist and molecular geneticists in order to identify genetic polymorphisms involved in IBD-associated CRC.The ultimate goal is to incorporate genotypes and clinical parameters into a predictive model that will refine the prediction of risk for CRC in colonic IBD.The challenge will be to translate these new findings into clinical practice and to determine appropriate preventive strategies in order to avoid CRC in IBD patients.The achieved knowledge may also be relevant for other inflammation-associated cancers.

Diagnosis and management of microscopic colitis

Microscopic colitis, comprising collagenous and lymphocytic colitis, is characterized clinically by chronic watery diarrhea, and a macroscopically normal colonic mucosa where diagnostic histopathological features are seen on microscopic examination. The annual incidence of each disorder is 4-6/100 000 inhabitants, with a peak incidence in 60-70-year-old individuals and a noticeable female predominance for collagenous colitis. The etiology is unknown. Chronic diarrhea, abdominal pain, weight loss, fatigue and fecal incontinence are common symptoms, which impair the health-related quality of life of the patient. There is an association with other autoimmune disorders such as celiac disease, diabetes mellitus, thyroid disorders and arthritis. Budesonide is the best-documented short-term treatment, but the optimal long-term strategy needs further study. The long-term prognosis is good and the risk of complications including colonic cancer is low.

Preventing Alcohol Consumption during Pregnancy: A Randomized Controlled Trial

The aim of this study is to report on a brief alcohol intervention for preventing drinking during pregnancy. The Women’s Organizations Committee on Alcohol and Drug Issues (WOCAD) in Sweden developed an informational brochure about alcohol during pregnancy, intended to reach pregnant women before their first visit at a prenatal clinic. A randomized controlled trial was conducted between 2004 and 2005 to measure whether the brochure had any effect. A total of 564 pregnant women between 17 and 46 years of age are included in the study. Differences between the intervention and control groups were analyzed with cross-tabulations and chi-squared tests. A multiple logistic regression analysis was also conducted to determine predictors of abstention from alcohol at the first prenatal visit. Findings show that significantly more of the women who received the brochure abstained completely from alcohol then of those who did not receive it (92% vs. 82%, p = 0.005). It was 2.6 times more likely that those who received the brochure had abstained completely from alcohol since pregnancy recognition at their first prenatal visit compared with those who did not receive it (OR = 2.6, CI 1.3 - 5.1, p = 0.005). We conclude that the informational brochure developed by WOCAD can be used in prenatal care to get more women to abstain from alcohol during pregnancy.

A short P-wave duration is associated with incident heart failure in the elderly: a 15 years follow-up cohort study

BACKGROUND Early identification of patients at risk of congestive heart failure(HF)may alter their poor prognosis.The aim was therefore to test whether simple electrocardiographic variables,the P-wave and PR-interval,could predict incident HF.METHODS The PIVUS(Prospective Investigation of the Vasculature in Uppsala Seniors)study(1016 individuals all aged 70 years,50%women)was used to identify predictors of HF.Subjects with prevalent HF,QRS duration≥130 ms,atrial tachyar-rhythmias,implanted pacemaker/defibrillator,second-and third-degree atrioventricular block or delta waves at baseline were excluded.Cox proportional hazard analysis was used to relate the PR interval,P-wave duration(Pdur)and amplitude(Pamp),measured in lead V1,to incident HF.Adjustment was performed for gender,RR-interval,beta-blocking agents,systolic blood pressure,body mass index and smoking.RESULTS Out of 836 subjects at risk,107 subjects were diagnosed with HF during a follow-up of 15 years.In the multivariate analysis,there was a strong U-shaped correlation between Pdur in lead V1 and incident HF(P=0.0001)which was significant for a Pdur<60 ms[HR=2.75;95%CI:1.87-4.06,at Pdur 40 ms]but not for prolonged Pdur.There was no significant relationship between incident HF and the PR-interval or the Pamp.A Pdur<60 ms improved discrimination by 3.7%when added to the tradi-tional risk factors including sex,RR-interval,beta-blocking agents,systolic blood pressure,BMI and smoking(P=0.048).CONCLUSIONS A short Pdur,an easily measured parameter on the ECG,may potentially be a useful marker of future HF,enabling its early detection and prevention,thus improving outcomes.

Maternal and Neonatal Death Review (MNDR): A Useful Approach to Identifying Appropriate and Effective Maternal and Neonatal Health Initiatives in Bangladesh

Objectives: To identify the effects of Maternal and Neonatal Death Review (MNDR) in terms of improving maternal and neonatal health at the community level in Bangladesh. Methods: Both quantitative and qualitative methods were undertaken for collecting data in Kashipur Union, Bangladesh. Death notifications from households, subsequent data collections from a focus-group discussion (FGD), a group discussion (GD) and in-depth interviews (IDIs) were obtained using structured tools and guidelines. Results: A total of four maternal deaths, 21 neonatal deaths and 15 still births were reported in the MNDR death notification system at Kashipur Union in 2010. Data were presented to local programme managers, who took various initiatives including awareness programmes, pregnancy registration, antenatal care, birth planning, and also the revitalization of a community clinic. The coverage of antenatal care, delivery in clinics, postnatal care and referral of complications increased through the active participation of the community. Community healthcare providers, care recipients and members of the community expressed satisfaction with the quality of maternal and neonatal services. In the preceding two years, maternal and neonatal deaths substantially reduced in Kashipur (in 2011 maternal death = 1, neonatal death = 20, still birth = 8;in 2012 maternal death = 1, neonatal death = 8, still birth = 13). Conclusions: The MNDR system successfully delivered notification of all maternal and neonatal deaths in the defined area and collected information for the formulation and implementation of specific interventions, which resulted in visible and tangible changes in care-seeking and client satisfaction.

Community Notification of Maternal, Neonatal Deaths and Still Births in Maternal and Neonatal Death Review (MNDR) System: Experiences in Bangladesh

Objectives: The aim of the study was to examine the process of community maternal, neonatal deaths and still births notification within the Bangladesh government health structure using the Maternal and Neonatal Death Review (MNDR) system. The study also explored the feasibility and acceptance of community death notification in the MNDR system. Methods: The study was under-taken in the Thakurgaon district of Bangladesh during 2010. During the study a mix of both qualitative and quantitative information was collected. A review of the documentation process of community death notification was undertaken and focus group discussions (FGDs) with community members, health care providers and managers in a sub-district were conducted, with in-depth interviews (IDIs) with district heath and family planning managers. Quantitative data were collected from community death notifications in the district during January to December 2010. Results: The death notification process was implemented by the government health care system within the Thakurgaon district. Field level health and family planning staff collected maternal and neonatal death information, recorded the death on the notification form and reported back to the Upazila (sub-district of the district) focal point at the Upazila health complex (primary health care centre). Community people were encouraged to share their death information to field level health staff. The health and family planning managers in the district periodically discussed the maternal and neonatal deaths and prepared remedial action plans in high death notified areas. In 2010, 59 maternal deaths, 739 neonatal deaths and 633 still births were reported in Thakurgaon district. District health and family planning departments performed community death notification as part of their routine daily work and integrated these procedures with other field level activities. Conclusion: Community death notification under the MNDR system was found to be achievable and acceptable at the district level using the existing government health system. The simple death notification process used to capture community level maternal, neonatal deaths and still births provides a guide for planning corrective actions for better health outcomes for the community.

Analytical Comparison of Resource Search Algorithms in Non-DHT Mobile Peer-to-Peer Networks

One of the key challenges in ad-hoc networks is the resource discovery problem.How efciently&quickly the queried resource/object can be resolved in such a highly dynamic self-evolving network is the underlying question?Broadcasting is a basic technique in the Mobile Ad-hoc Networks(MANETs),and it refers to sending a packet from one node to every other node within the transmission range.Flooding is a type of broadcast where the received packet is retransmitted once by every node.The naive ooding technique oods the network with query messages,while the random walk scheme operates by contacting subsets of each node’s neighbors at every step,thereby restricting the search space.Many earlier works have mainly focused on the simulation-based analysis of ooding technique,and its variants,in a wired network scenario.Although,there have been some empirical studies in peer-to-peer(P2P)networks,the analytical results are still lacking,especially in the context of mobile P2P networks.In this article,we mathematically model different widely used existing search techniques,and compare with the proposed improved random walk method,a simple lightweight approach suitable for the non-DHT architecture.We provide analytical expressions to measure the performance of the different ooding-based search techniques,and our proposed technique.We analytically derive 3 relevant key performance measures,i.e.,the avg.number of steps needed to nd a resource,the probability of locating a resource,and the avg.number of messages generated during the entire search process.

A system for underground road condition monitoring

Poor road conditions in underground mine tunnels can lead to decreased production efficiency and increased wear on production vehicles. A prototype system for road condition monitoring is presented in this paper to counteract this. The system consists of three components i.e. localization, road monitoring, and scheduling. The localization of vehicles is performed using a Rao-Blackwellized extended particle filter, combining vehicle mounted sensors with signal strengths of Wi Fi access points. Two methods for road monitoring are described: a Kalman filter used together with a model of the vehicle suspension system, and a relative condition measure based on the power spectral density. Lastly, a method for taking automatic action on an ill-conditioned road segment is proposed in the form of a rescheduling algorithm.The scheduling algorithm is based on the large neighborhood search and is used to integrate road service activities in the short-term production schedule while minimizing introduced production disturbances.The system is demonstrated on experimental data collected in a Swedish underground mine.

Mathematical Model Validation of Search Protocols in MP2P Networks

Broadcasting is a basic technique in Mobile ad-hoc network(MANET),and it refers to sending a packet from one node to every other node within the transmission range.Flooding is a type of broadcast where the received packet is retransmitted once by every node.The naive flooding technique,floods the network with query messages,while the random walk technique operates by contacting the subsets of every node’s neighbors at each step,thereby restricting the search space.One of the key challenges in an ad-hoc network is the resource or content discovery problem which is about locating the queried resource.Many earlier works have mainly focused on the simulation-based analysis of flooding,and its variants under a wired network.Although,there have been some empirical studies in peer-to-peer(P2P)networks,the analytical results are still lacking,especially in the context of P2P systems running over MANET.In this paper,we describe how P2P resource discovery protocols perform badly over MANETs.To address the limitations,we propose a new protocol named ABRW(Address Broadcast Random Walk),which is a lightweight search approach,designed considering the underlay topology aimed to better suit the unstructured architecture.We provide the mathematical model,measuring the performance of our proposed search scheme with different widely popular benchmarked search techniques.Further,we also derive three relevant search performance metrics,i.e.,mean no.of steps needed to find a resource,the probability of finding a resource,and the mean no.of message overhead.We validated the analytical expressions through simulations.The simulation results closely matched with our analyticalmodel,justifying our findings.Our proposed search algorithm under such highly dynamic self-evolving networks performed better,as it reduced the search latency,decreased the overall message overhead,and still equally had a good success rate.

英夫利昔单抗作为重度或中重度溃疡性结肠炎的补救疗法:一项随机、安慰剂对照试验

Background &Aims: Despite treatment with corticosteroids, severe to moderately severe attacks of ulcerative colitis have a high colectomy rate. We intended to find a rescue therapy other than cyclosporin A, which imposes a high risk of side effects and cyclosporine-related mortality. Methods: This was a randomized double-blind trial of infliximab or placebo in severe to moderately severe ulcerative colitis not responding to conventional treatment. Patients were randomized to infliximab/ placebo either on day 4 after the initiation of corticosteroid treatment if they fulfilled the index criteria for fulminant ulcerative colitis on day 3 or on day 6-8 if they fulfilled index criteria on day 5-7 for a severe or moderately severe acute attack of ulcerative colitis. Results were analyzed according to the intention-to-treat principle. The primary end point was colectomy or death 3 months after randomization. Secondary end points were clinical and endoscopic remission at that time in patients who did not undergo operation. Results: Forty-five patients were included (24 infliximab and 21 placebo). No patient died. Seven patients in the infliximab group and 14 in the placebo group had a colectomy (P =. 017; odds ratio, 4.9; 95%confidence interval, 1.4-17) within 3 months after randomization. No serious side effects occurred. Three patients in the placebo group required operation for septic complications. Conclusions: Infliximab 4-5 mg/kg is an effective and safe rescue therapy in patients experiencing an acute severe or moderately severe attack of ulcerative colitis not responding to conventional treatment.

母亲孕期饮用牛奶和新生儿体重的关系

目的:调查低出生体重(【2.5kg,LBW)、胎儿宫内发育迟缓(IUGR)及早产(胎龄【37周)与母亲孕期牛奶摄入量的关系。方法:在瑞典东南部进行观察性研究,选择两年内ABIS(瑞典东南部所有出生婴儿研究计划)部分婴儿及其母亲构成的母子对作为研究对象,采用问卷调查收集母亲怀孕期间牛奶饮用量和婴儿的体重。IUGR资料来自瑞典医疗机构的出生登记。

8000例儿童中便秘及其他胃肠道症状的流行病学调查研究

Aim: Adult studies indicate that gastrointestinal symptoms vary with sex and socioeconomic status. We examined socioeconomic factors, infant sex, smoking and gastrointestinal symptoms, especially constipation, in 2.5 year- old children. Methods: This study was part of a prospective cohort study of children born 01.10.97- 01.10.99 (the ABIS study; All Babies in Southeast Sweden). Socioeconomic factors, infant sex, smoking were analyzed vs. constipation, diarrhoea, anorexia, abdominal pain, meteorism and vomiting using logistic regression. All data were obtained through questionnaires distributed at infant birth, at 1 and 2.5 years of age. Results: Out of 8341 children, 539 (6.5% ) suffered from constipation. In a backward stepwise regression analysis (AOR; and 95% CI AOR = are given within brackets), constipation correlated with low maternal education (1.60; 1.08- 2.35), female sex (1.52; 1.23- 1.85), living in a large community with > 3000 inhabitants (1.35; 1.09- 1.64) and having no older siblings (1.28; 1.04- 1.59). Smoking during pregnancy was linked to diarrhoea (multivariate analysis: 1.76; 1.02- 3.02), anorexia (univariate analysis: 1.43; 1.09- 1.87) and meteorism (univariate analysis: 1.58; 1.11- 2.27). Adjusting for confounders, paracetamol use was linked to a five- fold increased risk of anorexia (5.12; 1.26- 20.70). Conclusions: This study indicates that socioeconomic status, infant sex and parental smoking, are associated with gastrointestinal symptoms in children.

Eosinophil associated genes in the inflammatory bowel disease 4 region:Correlation to inflammatory bowel disease revealed

AIM:To study the association between inflammatory bowel disease(IBD) and genetic variations in eosinophil protein X(EPX) and eosinophil cationic protein(ECP).METHODS:DNA was extracted from ethylene diamine tetraacetic acid blood of 587 patients with Crohn's disease(CD),592 with ulcerative colitis(UC) and 300 healthy subjects.The EPX405(G > C,rs2013109),ECP434(G > C,rs2073342) and ECP562(G > C,rs2233860) gene polymorphisms were analysed,by the 5'-nuclease allelic discrimination assay.For determination of intracellular content of EPX and ECP in granulocytes,39 blood samples was collected and extracted with a buffer containing cetyltrimethylammonium bromide.The intracellular content of EPX was analysed using an enzyme-linked immunosorbent assay.The intracellular content of ECP was analysed with the UniCAP system as described by the manufacturer.Statistical tests for calculations of results were χ 2 test,Fisher's exact test,ANOVA,Student-Newman-Keuls test,and Kaplan-Meier survival curve with Log-rank test for trend,the probability values of P < 0.05 were considered statistically significant.RESULTS:The genotype frequency for males with UC and with an age of disease onset of ≥ 45 years(n = 57) was for ECP434 and ECP562,GG = 37%,GC = 60%,CC = 4% and GG = 51%,GC = 49%,CC = 0% respectively.This was significantly different from the healthy subject's genotype frequencies of ECP434(GG = 57%,GC = 38%,CC = 5%;P = 0.010) and ECP562(GG = 68%,GC = 29%,CC = 3%;P = 0.009).The genotype frequencies for females,with an age of disease onset of ≥ 45 years with CD(n = 62),was for the ECP434 and ECP562 genotypes GG = 37%,GC =52%,CC = 11% and GG = 48%,GC = 47% and CC = 5% respectively.This was also statistically different from healthy controls for both ECP434(P = 0.010) and ECP562(P = 0.013).The intracellular protein concentration of EPX and ECP was calculated in μg/10 6 eosinophils and then correlated to the EPX 405 genotypes.The protein content of EPX was highest in the patients with the CC genotype of EPX405(GG = 4.65,GC = 5.93,and CC = 6.57) and for ECP in the patients with the GG genotype of EPX405(GG = 2.70,GC = 2.47 and CC = 1.90).ANOVA test demonstrated a difference in intracellular protein content for EPX(P = 0.009) and ECP(P = 0.022).The age of disease onset was linked to haplotypes of the EPX405,ECP434 and ECP562 genotypes.Kaplan Maier curve showed a difference between haplotype distributions for the females with CD(P = 0.003).The highest age of disease onset was seen in females with the EPX405CC,ECP434GC,ECP562CC haplotype(34 years) and the lowest in females with the EPX405GC,ECP434GC,ECP562GG haplotype(21 years).For males with UC there was also a difference between the highest and lowest age of the disease onset(EPX405CC,ECP434CC,ECP562CC,mean 24 years vs EPX405GC,ECP434GC,ECP562GG,mean 34 years,P = 0.0009).The relative risk for UC patients with ECP434 or ECP562-GC /CC genotypes to develop dysplasia/cancer was 2.5(95%CI:1.2-5.4,P = 0.01) and 2.5(95%CI:1.1-5.4,P = 0.02) respectively,compared to patients carrying the GG-genotypes.CONCLUSION:Polymorphisms of EPX and ECP are associated to IBD in an age and gender dependent manner,suggesting an essential role of eosinophils in the pathophysiology of IBD.

血栓性血小板减少性紫癜患者治疗的可能性和有限性

血栓性血小板减少性紫癜(TTP)是一种以血栓、溶血、红细胞碎片、血小板减少及中枢神经系统(CNS)和肾脏功能障碍、发热为特征的影响小血管的疾病.