The cGAS-STING-interferon regulatory factor 7 pathway regulates neuroinflammation in Parkinson's disease

Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial cells.Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype.In addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1.Taken together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.

Health risk assessment of trace metal(loid)s in agricultural soils based on Monte Carlo simulation coupled with positive matrix factorization model in Chongqing, southwest China

This study aimed to investigate the pollution characteristics, source apportionment, and health risks associated with trace metal(loid)s(TMs) in the major agricultural producing areas in Chongqing, China. We analyzed the source apportionment and assessed the health risk of TMs in agricultural soils by using positive matrix factorization(PMF) model and health risk assessment(HRA) model based on Monte Carlo simulation. Meanwhile, we combined PMF and HRA models to explore the health risks of TMs in agricultural soils by different pollution sources to determine the priority control factors. Results showed that the average contents of cadmium(Cd), arsenic (As), lead(Pb), chromium(Cr), copper(Cu), nickel(Ni), and zinc(Zn) in the soil were found to be 0.26, 5.93, 27.14, 61.32, 23.81, 32.45, and 78.65 mg/kg, respectively. Spatial analysis and source apportionment analysis revealed that urban and industrial sources, agricultural sources, and natural sources accounted for 33.0%, 27.7%, and 39.3% of TM accumulation in the soil, respectively. In the HRA model based on Monte Carlo simulation, noncarcinogenic risks were deemed negligible(hazard index <1), the carcinogenic risks were at acceptable level(10^(-6)<total carcinogenic risk ≤ 10^(-4)), with higher risks observed for children compared to adults. The relationship between TMs, their sources, and health risks indicated that urban and industrial sources were primarily associated with As, contributing to 75.1% of carcinogenic risks and 55.7% of non-carcinogenic risks, making them the primary control factors. Meanwhile, agricultural sources were primarily linked to Cd and Pb, contributing to 13.1% of carcinogenic risks and 21.8% of non-carcinogenic risks, designating them as secondary control factors.

Sorl1 knockout inhibits expression of brain-derived neurotrophic factor:involvement in the development of late-onset Alzheimer's disease

Sortilin-related receptor 1(SORL1)is a critical gene associated with late-onset Alzheimer’s disease.SORL1 contributes to the development and progression of this neurodegenerative condition by affecting the transport and metabolism of intracellularβ-amyloid precursor protein.To better understand the underlying mechanisms of SORL1 in the pathogenesis of late-onset Alzheimer s disease,in this study,we established a mouse model of SorI1 gene knockout using cluste red regularly inters paced short palindro mic repeats-associated protein 9 technology.We found that Sorl1-knocko ut mice displayed deficits in learning and memory.Furthermore,the expression of brain-derived neurotrophic factor was significantly downregulated in the hippocampus and co rtex,and amyloidβ-protein deposits were observed in the brains of 5orl1-knockout mice.In vitro,hippocampal neuronal cell synapses from homozygous Sorl1-knockout mice were impaired.The expression of synaptic proteins,including Drebrin and NR2B,was significantly reduced,and also their colocalization.Additionally,by knocking out the Sorl1 gene in N2a cells,we found that expression of the N-methyl-D-aspartate receptor,NR2B,and cyclic adenosine monophosphate-response element binding protein was also inhibited.These findings suggest that SORL1 participates in the pathogenesis of late-onset Alzheimer s disease by regulating the N-methyl-D-aspartate receptor NR2B/cyclic adenosine monophosphate-response element binding protein signaling axis.

Interplay between microglia and environmental risk factors in Alzheimer's disease

Alzheimer s disease,among the most common neurodegenerative disorders,is chara cterized by progressive cognitive impairment.At present,the Alzheimer’s disease main risk remains genetic ris ks,but major environmental fa ctors are increasingly shown to impact Alzheimer’s disease development and progression.Microglia,the most important brain immune cells,play a central role in Alzheimer’s disease pathogenesis and are considered environmental and lifestyle"sensors."Factors like environmental pollution and modern lifestyles(e.g.,chronic stress,poor dietary habits,sleep,and circadian rhythm disorde rs)can cause neuroinflammato ry responses that lead to cognitive impairment via microglial functioning and phenotypic regulation.However,the specific mechanisms underlying interactions among these facto rs and microglia in Alzheimer’s disease are unclear.Herein,we:discuss the biological effects of air pollution,chronic stress,gut micro biota,sleep patterns,physical exercise,cigarette smoking,and caffeine consumption on microglia;consider how unhealthy lifestyle factors influence individual susceptibility to Alzheimer’s disease;and present the neuroprotective effects of a healthy lifestyle.Toward intervening and controlling these environmental risk fa ctors at an early Alzheimer’s disease stage,understanding the role of microglia in Alzheimer’s disease development,and to rgeting strategies to to rget microglia,co uld be essential to future Alzheimer’s disease treatments.

Exercise and exerkine upregulation:Brain-derived neurotrophic factor as a potential non-pharmacological therapeutic strategy for Parkinson’s disease

Physical activity and exercise have several beneficial roles in enhancing both physiological and psychological well-being of an individual.In addition to aiding the regulation of aerobic and anaerobic metabolism,exercise can stimulate the synthesis of exerkine hormones in the circulatory system.Among several exerkines that have been investigated for their therapeutic potential,Brain-derived neurotrophic factor(BDNF)is considered the most promising candidate,especially in the management of neurodegenerative diseases.Owing to the ability of physical activity to enhance BDNF synthesis,several experimental studies conducted so far have validated this hypothesis and produced satisfactory results at the pre-clinical level.This review highlights some of the recent animal model studies that have evaluated the efficiency of exercise in enhancing BDNF synthesis and promoting neuroprotective effects.Further,this review focuses on understanding the therapeutic benefits of exercise-induced exerkine synthesis as a non-pharmacological strategy in Parkinson’s disease(PD).Regarding physical activity and exerkine induction,the neuromuscular electrical stimulation(NMES)strategy could be considered as an alternate treatment modality for patients affected with PD.

Prevalence and risk factors of depression among patients with perianal fistulizing Crohn’s disease

BACKGROUND Psychological distress,especially depression,associated with perianal fistulizing Crohn’s disease(PFCD)is widespread and refractory.However,there is a surprising paucity of studies to date that have sought to identify the prevalence and risk factors of depression associated with PFCD.AIM To estimate the prevalence of depressive symptoms and investigate the depression-related risk factors in patients with PFCD.METHODS The study was conducted in the form of survey and clinical data collection via questionnaire and specialized medical staff.Depressive symptoms,life quality,and fatigue severity of patients with PFCD were assessed by Patient Health Questionnaire-9,Inflammatory Bowel Disease Patient Quality of Life Questionnaire(IBDQ),and Inflammatory Bowel Disease(IBD)Fatigue Patient Self-assessment Scale.The basic demographic information,overall disease features,perianal clinical information,and laboratory inflammation indicators were also gathered.Multivariate regression analysis was ultimately used to ascertain the risk factors of depression associated with PFCD.RESULTS A total of 123 patients with PFCD were involved,and 56.91%were suffering from depression.According to multivariate logistic regression analysis,Perianal Disease Activity Index(PDAI)score[odds ratio(OR)=0.69,95%confidence interval(CI):0.50 to 0.95],IBDQ score(OR=0.93,95%CI:0.88 to 0.97),modified Van Assche index(OR=1.24,95%CI:1.01 to 1.53),and IBD Fatigue score(OR=1.72,95%CI:1.23 to 2.42)were independent risk factors of depression-related prevalence among patients with PFCD(P<0.05).Multiple linear regression analysis revealed that the increasing perianal modified Van Assche index(βvalue=0.166,95%CI:0.02 to 0.31)and decreasing IBDQ score(βvalue=-0.116,95%CI:-0.14 to-0.09)were independently associated with the severity of depression(P<0.05).CONCLUSION Depressive symptoms in PFCD patients have significantly high prevalence.PDAI score,modified Van Assche index,quality of life,and fatigue severity were the main independent risk factors.

Epidemiological Aspects of Obesity, Overweight and Cardiovascular Risk Factors at Associes in Semi-Urban Areas (Case of Sébikotane)

Introduction: Obesity and overweight are a public health problem. The general objective was to determine the epidemiological aspects of obesity, overweight and associated risk factors in a semi-urban environment. Patients and Methods: This was a cross-sectional, descriptive study conducted on November 28 and 29, 2023 in Sébikotane. It focused on volunteers for screening for chronic non-communicable diseases. Epidemiological and clinical data were evaluated. Results: One hundred and twenty-nine cases of obesity were recorded (28%). Two hundred and eighty-two cases were overweight or obese (61.3%). The mean age was 49.55 years, with a standard deviation of 12.41 years. The age group [40 - 49 years] was the most representative, with 85 cases (30.1%), and the majority were female, with 264 cases (93.6%). Primary education was the most common, with 75 cases (46.3%). Grade 1 obesity concerned ninety-seven cases (75.2%), and diabetes was present in thirty cases (23%). Hypertension was present in ninety-five cases (33.7%). Obesity was more marked in the age group [40 - 49 years] with 45 cases (36%). Conclusion: Obesity and overweight are a major cause of morbidity and mortality. The development and implementation of a prevention and management program is essential.

Surgical and non-surgical risk factors affecting the insufficiency of ileocolic anastomosis after first-time surgery in Crohn’s disease patients

BACKGROUND Crohn's disease(CD)often necessitates surgical intervention,particularly when it manifests in the terminal ileum and ileocecal valve.Despite undergoing radical surgery,a subset of patients experiences recurrent inflammation at the anasto-motic site,necessitating further medical attention.AIM To investigate the risk factors associated with anastomotic insufficiency following ileocecal resection in CD patients.METHODS This study enrolled 77 patients who underwent open ileocolic resection with pri-mary stapled anastomosis.Patients were stratified into two groups:Group I co-mprised individuals without anastomotic insufficiency,while Group II included patients exhibiting advanced anastomotic destruction observed endoscopically or those requiring additional surgery during the follow-up period.Surgical and non-surgical factors potentially influencing anastomotic failure were evaluated in both cohorts.RESULTS Anastomotic insufficiency was detected in 12 patients(15.6%),with a mean time interval of 30 months between the initial surgery and recurrence.The predomi-nant reasons for re-intervention included stenosis and excessive perianastomotic lesions.Factors associated with a heightened risk of anastomotic failure encompassed prolonged postoperative obstruction,anastomotic bleeding,and clinically confirmed micro-leakage.Additionally,patients in Group II exhibited preoperative malnutrition and early recurrence of symptoms related to CD.CONCLUSION Successful surgical outcomes hinge on the attainment of a fully functional anastomosis,optimal metabolic status,and clinical remission of the underlying disease.Vigilant endoscopic surveillance following primary resection facilitates the timely identification of anastomotic failure,thereby enabling noninvasive interventions.

Influencing factors and preventive measures of infectious complications after intestinal resection for Crohn’s disease

The incidence of Crohn’s disease(CD)has increased in recent years,with most patients requiring intestinal resection.Complications after intestinal resection for CD can lead to poor prognosis and recurrence,among which infectious complic-ations are the most common.This study aimed to investigate the common risk factors,including medications,preoperative nutritional status,surgery-related factors,microorganisms,lesion location and type,and so forth,causing infectious complications after intestinal resection for CD,and to propose corresponding preventive measures.The findings provided guidance for identifying suscept-ibility factors and the early intervention and prevention of infectious complic-ations after intestinal resection for CD in clinical practice.

Gender disparities and woman-specific trends in Barrett’s esophagus in the United States:An 11-year nationwide populationbased study

BACKGROUND Barrett's esophagus(BE)is a known premalignant precursor to esophageal adenocarcinoma(EAC).The prevalence rates continue to rise in the United States,but many patients who are at risk of EAC are not screened.Current practice guidelines include male gender as a predisposing factor for BE and EAC.The population-based clinical evidence regarding female gender remains limited.AIM To study comparative trends of gender disparities in patients with BE in the United States.METHODS A nationwide retrospective study was conducted using the 2009-2019 National Inpatient Sample(NIS)database.Patients with a primary or secondary diagnosis code of BE were identified.The major outcome of interest was determining the gender disparities in patients with BE.Trend analysis for respective outcomes for females was also reported to ascertain any time-based shifts.RESULTS We identified 1204190 patients with BE for the study period.Among the included patients,717439(59.6%)were men and 486751(40.4%)were women.The mean age was higher in women than in men(67.1±0.4 vs 66.6±0.3 years,P<0.001).The rate of BE per 100000 total NIS hospitalizations for males increased from 144.6 in 2009 to 213.4 in 2019(P<0.001).The rate for females increased from 96.8 in 2009 to 148.7 in 2019(P<0.001).There was a higher frequency of obesity among women compared to men(17.4%vs 12.6%,P<0.001).Obesity prevalence among females increased from 12.3%in 2009 to 21.9%in 2019(P<0.001).A lower prevalence of smoking was noted in women than in men(20.8%vs 35.7%,P<0.001).However,trend analysis showed an increasing prevalence of smoking among women,from 12.9%in 2009 to 30.7%in 2019(P<0.001).Additionally,there was a lower prevalence of alcohol abuse,Helicobacter pylori(H.pylori),and diabetes mellitus among females than males(P<0.001).Trend analysis showed an increasing prevalence of alcohol use disorder and a decreasing prevalence of H.pylori and diabetes mellitus among women(P<0.001).CONCLUSION The prevalence of BE among women has steadily increased from 2009 to 2019.The existing knowledge concerning BE development has historically focused on men,but our findings show that the risk in women is not insignificant.

Gamma-glutamyl transferase 5 overexpression in cerebrovascular endothelial cells improves brain pathology,cognition,and behavior in APP/PS1 mice

In patients with Alzheimer’s disease,gamma-glutamyl transferase 5(GGT5)expression has been observed to be downregulated in cerebrovascular endothelial cells.However,the functional role of GGT5 in the development of Alzheimer’s disease remains unclear.This study aimed to explore the effect of GGT5 on cognitive function and brain pathology in an APP/PS1 mouse model of Alzheimer’s disease,as well as the underlying mechanism.We observed a significant reduction in GGT5 expression in two in vitro models of Alzheimer’s disease(Aβ_(1-42)-treated hCMEC/D3 and bEnd.3 cells),as well as in the APP/PS1 mouse model.Additionally,injection of APP/PS1 mice with an adeno-associated virus encoding GGT5 enhanced hippocampal synaptic plasticity and mitigated cognitive deficits.Interestingly,increasing GGT5 expression in cerebrovascular endothelial cells reduced levels of both soluble and insoluble amyloid-βin the brains of APP/PS1 mice.This effect may be attributable to inhibition of the expression ofβ-site APP cleaving enzyme 1,which is mediated by nuclear factor-kappa B.Our findings demonstrate that GGT5 expression in cerebrovascular endothelial cells is inversely associated with Alzheimer’s disease pathogenesis,and that GGT5 upregulation mitigates cognitive deficits in APP/PS1 mice.These findings suggest that GGT5 expression in cerebrovascular endothelial cells is a potential therapeutic target and biomarker for Alzheimer’s disease.

Estimating Functional Brain Network with Low-Rank Structure via Matrix Factorization for MCI/ASD Identification

Functional brain networks (FBNs) provide a potential way for understanding the brain organizational patterns and diagnosing neurological diseases. Due to its importance, many FBN construction methods have been proposed currently, including the low-order Pearson’s correlation (PC) and sparse representation (SR), as well as the high-order functional connection (HoFC). However, most existing methods usually ignore the information of topological structures of FBN, such as low-rank structure which can reduce the noise and improve modularity to enhance the stability of networks. In this paper, we propose a novel method for improving the estimated FBNs utilizing matrix factorization (MF). More specifically, we firstly construct FBNs based on three traditional methods, including PC, SR, and HoFC. Then, we reduce the rank of these FBNs via MF model for estimating FBN with low-rank structure. Finally, to evaluate the effectiveness of the proposed method, experiments have been conducted to identify the subjects with mild cognitive impairment (MCI) and autism spectrum disorder (ASD) from norm controls (NCs) using the estimated FBNs. The results on Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset and Autism Brain Imaging Data Exchange (ABIDE) dataset demonstrate that the classification performances achieved by our proposed method are better than the selected baseline methods.

Overexpression of lentivirus-mediated glial cell line-derived neurotrophic factor in bone marrow stromal cells and its neuroprotection for the PC12 cells damaged by lactacystin

Objective To construct recombinant lentiviral vectors for gene delivery of the glial cell line-derived neurotropnic factor （GDNF）, and evaluate the neuroprotective effect of GDNF on lactacystin-damaged PC12 cells by transfecting it into bone marrow stromal cells （BMSCs）. Methods pLenti6/V5-GDNF plasmid was set up by double restriction enzyme digestion and ligation, and then the plasmid was transformed into Top10 cells. Purified pLenti6/V5-GDNF plasmids from the positive clones and the packaging mixture were cotransfected to the 293FT packaging cell line by Lipofectamine2000 to produce lentivirus, then the concentrated virus was transduced to BMSCs. Overexpression of GDNF in BMSCs was tested by RT-PCR, ELISA and immunocytochemistry, and its neuroprotection for lactacystin-damaged PC12 cells was evaluated by MTT assay. Results Virus stock of GDNF was harvested with the titer of 5.6×10^5 TU/mL. After tmnsduction, GDNF-BMSCs successfully secreted GDNF to supematant with nigher concentration （800 pg/mL） than BMSCs did （less than 100 pg/mL）. The supematant of GDNF-BMSCs could significantly alleviate the damage of PC12 cells induced by lactacystin （10 μmol/L）. Conclusion Overexpression of lentivirus-mediated GDNF in the BMSCs cells can effectively protect PC12 cells from the injury by the proteasome inhibitor.

改进粒子群优化Takagi-Sugeno模糊径向基函数神经网络的非线性系统建模

针对复杂非线性系统建模的难点问题,提出了一种基于改进的粒子群优化算法(PSO)优化的T-S模糊径向基函数(RBF)神经网络的新型系统建模算法。该算法将T-S模糊模型良好的可解释性及RBF神经网络的自学习能力相结合,构成T-S模糊RBF神经网络用于系统建模,并采用动态调整惯性权重的改进的PSO算法结合递推最小二乘算法实现网络参数的优化调整。首先,利用所提算法进行了非线性多维函数的逼近仿真,仿真结果均方差(MSE)为0.00017,绝对值误差不大于0.04,逼近精度较高;又将该算法用于建立动态流量软测量模型,并进行了相关的实验研究,动态流量测量结果平均绝对误差小于0.15 L/min,相对误差为1.97%,基本满足测量要求,并优于已有算法。上述仿真及实验研究结果表明,所提算法对于复杂非线性系统具有较高的建模精度和良好的自适应性。

一类新的Takagi-Sugeno模糊时滞系统的稳定性准则

本文提出一种新的时滞划分方法—变时滞划分法,以解决连续延时Takagi-Sugeno模糊系统的稳定性和镇定性问题.不同于已有的文献,用可变参数将时变时滞区间[0,d(t)]划分为若干个可变子区间,并得出模糊时滞系统的新的时滞相关稳定性准则.本文提出的新方法能充分利用时滞子区间的内部信息,因此新的时滞相关稳定性准则比以往结果具有更小的保守性.基于Lyapunov稳定性理论,以线性矩阵不等式形式给出T--S模糊系统的新的时滞相关稳定性准则,并将稳定性和镇定性研究结果扩展到具有不确定参数的T--S模糊系统.仿真实例证明了本文方法降低保守性的有效性.

车辆主动悬架自适应变论域T-S模糊控制研究

针对传统变论域模糊控制存在过度依赖专家经验、伸缩因子参数不能自适应调整的问题,提出一种车辆主动悬架自适应变论域T-S模糊控制策略,从而提高车辆的行驶平顺性。结合神经网络和T-S模糊推理建立基于自适应神经模糊推理的一阶T-S模糊控制器,利用神经网络的自学习特性产生完善的模糊规则,进而在传统函数型伸缩因子的基础上,将系统误差和误差变化率作为动态参数引入伸缩因子中,实现伸缩因子参数的自适应调整,解决了传统函数型伸缩因子因参数确定难度大导致控制效果差的问题。通过随机工况下的仿真分析和基于相似理论的缩尺实验,对所提出算法的有效性和工况自适应性进行了验证。结果表明,所提出的自适应变论域T-S模糊控制策略具有较强的工况适应性,在不同车速、路面激励下均可有效提高车辆的平顺性并保证轮胎接地安全性。

帕金森病患者免疫球蛋白、Th9亚群水平变化及其与IGF-1、S-100B蛋白的相关性

目的:研究帕金森病(PD)患者免疫球蛋白(IgG、IgA和IgM)、辅助性T细胞亚群Th9水平变化及其与胰岛素生长因子-1(IGF-1)、S-100B蛋白的相关性。方法:选取2020年12月至2022年12月期间在河北省中医院确诊的108例PD患者,将其作为研究组,并根据患者病变程度分为轻度组(35例)、中度组(44例)和重度组(29例);另选108例健康成人作为对照组。对比研究组和对照组免疫球蛋白和Th9亚群水平,以及轻度组、中度组及重度组免疫球蛋白、Th9亚群、IGF-1和S-100B蛋白水平,采用Pearson相关性分析免疫球蛋白、Th9亚群和IGF-1、S-100B蛋白的相关性。采用Spearman相关性分析PD患者疾病程度和所有差异指标间的相关性。结果:研究组IgM水平较对照组低,且重度组低于中度组,中度组低于轻度组(P<0.05);研究组IgG、IgA、IL-9和Th9亚群水平较对照组高,且重度组高于中度组,中度组高于轻度组(P<0.05)。重度组IGF-1水平低于中度组,中度组低于轻度组;重度组S-100B蛋白水平高于中度组,中度组高于轻度组(P<0.05)。Pearson相关性分析结果显示,PD患者IgM水平与IGF-1水平呈正相关,与S-100B蛋白水平呈负相关;IgG、IgA、IL-9和Th9亚群水平均与IGF-1水平呈负相关,与S-100B蛋白水平呈正相关(P<0.05)。Spearman相关性分析结果显示,PD患者疾病程度与IgM、IGF-1水平呈负相关,与S-100B蛋白、IgG、IgA、IL-9和Th9亚群水平呈正相关(P<0.05)。结论:PD患者IgM水平降低,IgG、IgA、Th9亚群水平升高,且其水平变化与IGF-1、S-100B明显相关,可以用于评估病情的严重程度。

Q-factor estimation in CMP gather and the continuous spectral ratio slope method

The attenuation factor or quality factor(Q-factor or Q) has been used to measure the energy attenuation of seismic waves propagating in underground media. Many methods are used to estimate the Q-factor. We propose a method to calculate the Q-factor based on the prestack Q-factor inversion and the generalized S-transform. The proposed method specifies a standard primary wavelet and calculates the cumulative Q-factors; then, it finds the interlaminar Q-factors using the relation between Q and offset(QVO) and the Dix formula. The proposed method is alternative to methods that calculate interlaminar Q-factors after horizon picking. Because the frequency spectrum of each horizon can be extracted continuously on a 2D time–frequency spectrum, the method is called the continuous spectral ratio slope(CSRS) method. Compared with the other Q-inversion methods, the method offers nearly effortless computations and stability, and has mathematical and physical significance. We use numerical modeling to verify the feasibility of the method and apply it to real data from an oilfield in Ahdeb, Iraq. The results suggest that the resolution and spatial stability of the Q-profile are optimal and contain abundant interlaminar information that is extremely helpful in making lithology and fluid predictions.

Prognostic significance of S100A4 and vascular endothelial growth factor expression in pancreatic cancer

AIM: To investigate the expression of vascular endothelial growth factor (VEGF) and calcium-binding protein S100A4 in pancreatic cancer and their relationship to the clinicopathological parameters and prognosis of pancreatic cancer. METHODS: Expression status of VEGF and S100A4 was examined in 62 surgical specimens of primary pancreatic cancer by immunohistochemistry. Correlation between the expression of VEGF and S100A4 and clinicopathological parameters was analyzed. RESULTS: Thirty-eight of 62 (61.3%) specimens of primary pancreatic cancer were positive for S100A4. Thirty-seven (59.7%) specimens showed positive expression of VEGF. The positive correlation between S100A4 and VEGF expression was significant in cancer tissues (P < 0.001). S100A4 expression was significantly correlated with tumor size, TNM stage and poorer prognosis. VEGF expression had a significant correlation with poorer prognosis. The prognosis of 17 S100A4-and VEGF-negative cancer patients was significantly better than that of other patients (P < 0.05). Distant metastasis (P = 0.001), S100A4-(P = 0.008) and VEGF-positive expression (P = 0.016) were significantly independent prognostic predictors (P < 0.05). CONCLUSION: Over-expression of S100A4 and VEGF plays an important role in the development of pancreatic cancer. Combined examination of the two molecules might be useful in evaluating the outcome of patients with pancreatic cancer.

Safety of anti-tumor necrosis factor therapy in inflammatory bowel disease

Inflammatory bowel disease (IBD), in particular Crohn's disease refractory to conventional therapy, fistulizing Crohn's disease and chronic active ulcerative colitis, generally respond well to anti-tumor necrosis factor (TNF) therapy. However, serious side effects do occur, necessitating careful monitoring of therapy. Potential side effects of anti-TNF therapy include opportunistic infections, which show a higher incidence when concomitant immunosuppression is used. Furthermore, antibody formation against anti-TNF is associated with decreased efficacy and an increased frequency of infusion reactions. The hypothesis of a slightly increased risk of lymphomas in IBD patients treated with anti TNF-therapy is debatable, since most studies lack the specific design to properly address this issue. Alarmingly, the occurrence of hepatosplenic T-cell lymphomas coincides with combined immunosuppressive therapy. Despite the potential serious side effects, anti-TNF therapy is an effective and relatively safe treatment option for refractory IBD. Future research is needed to answer important questions, such as the long-term risk of malignancies, safety during pregnancy, when to discontinue and when to switch anti-TNF therapy, as well as to determine the balance between therapeutic and toxic effects.