1-磷酸鞘胺醇受体3参与巨噬细胞迁移及脓毒症诱导的心肌损伤

目的探讨巨噬细胞中1-磷酸鞘胺醇受体(sphingosine 1-phosphate receptor,S1PR)的表达及其作用,观察干预S1PR3(S1P3)对脂多糖诱导的心肌损伤的影响。方法传代培养小鼠Ana-1巨噬细胞,给予脂多糖(lipopolysaccharide,LPS,100 ng/ml)刺激或S1P3特异性抑制剂CAY-10444(10μmol/L)干预,细胞随机分为对照组、LPS组、CAY-10444组、CAY-10444预处理2h+LPS组,Transwell小室观测巨噬细胞迁移,蛋白免疫印迹检测巨噬细胞S1PR的表达,并检测p-Akt/Akt蛋白水平。在体实验,6~8周龄雄性C57/B6小鼠,随机分为对照组、LPS组、CAY-10444组、CAY-10444干预+LPS组,每组12只,LPS(10 mg/kg)腹腔注射,或CAY-10444 1 mg/kg于LPS诱导后30 min腹腔注射干预,24 h后取心脏组织HE染色观察病理改变,免疫组化染色观察巨噬细胞浸润程度以及炎症因子的表达情况,实时荧光定量PCR检测心肌损伤标记分子BNP、巨噬细胞表面分子F4/80、炎症因子TNF-α、IL-1β、IL-6的mRNA水平。结果与对照组比较,LPS诱导巨噬细胞大量迁移S1P3蛋白表达增加(P0.01),p-Akt Ser473/Akt表达上调(P0.01);与LPS组相比,S1P3抑制剂CAY-10444干预后再给予LPS刺激,巨噬细胞迁移被抑制(P0.01),p-Akt Ser473/Akt表达也降低(P0.01);在体实验,LPS诱导小鼠后BNP mRNA水平明显上调(P0.01),同时F4/80以及炎症因子TNF-α、IL-1β、IL-6的mRNA水平上调(P0.01),HE染色可见心肌损伤及炎细胞浸润,免疫组化染色法显示F4/80及炎症因子的大量阳性表达(P0.01);使用S1P3抑制剂后,与LPS组比较,心肌损伤减轻免疫组化中巨噬细胞减少(P0.01),炎症因子表达降低(P0.01),BNP mRNA水平降低(P0.01),F4/80以及TNF-α、IL-1β、IL-6的mRNA水平也明显降低(P0.01)。结论抑制巨噬细胞S1P3表达可抑制巨噬细胞的迁移并提示p-Akt/Akt与了这一过程,此外,S1P3抑制剂的干预可有效减轻LPS诱导的心肌损伤。     

老年2型糖尿病并发ACS患者血清GGT与慢血流-无复流的相关性及其对预后的影响

目的探讨老年2型糖尿病(T2DM)并发急性冠脉综合征(ACS)患者血清γ谷氨酰胺转肽酶(GGT)水平与经皮冠状动脉介入(PCI)治疗术后冠脉慢血流-无复流的相关性及其对预后的影响。方法选取188例诊断为ACS并行急诊PCI的老年T2DM患者,根据TIMI血流分级和校正的TIMI血流帧计数(c TFC)方法评价冠脉血流分为正常血流组(156例)和慢血流-无复流组(32例),分析GGT及其他危险因素与冠脉慢血流-无复流的相关性和主要不良心血管事件(MACE)的发生率。结果慢血流-无复流组的血清GGT水平高于正常血流组[(49±18)U/L vs.(31±13)U/L,P0.01]。相关分析结果显示,血清GGT与冠脉慢血流-无复流呈正相关(r=0.389,P0.01)。血清GGT与PCI术后冠脉慢血流-无复流、住院期间及术后12个月MACE独立相关(分别OR=1.093,95%CI:1.058~1.129,P0.01;OR=1.047,95%CI:1.012~1.082,P0.05及OR=1.058,95%CI:1.028~1.089,P0.01)。结论老年T2DM并发ACS患者血清GGT水平与冠脉慢血流-无复流相关,血清GGT可能是预测冠脉风险的评价指标。     

HBV endemicity in Mexico is associated with HBV genotypes H and G

Hepatitis B virus(HBV)genotypes have distinct genetic and geographic diversity and may be associated with specific clinical characteristics,progression,severity of disease and antiviral response.Herein,we provide an updated overview of the endemicity of HBV genotypes H and G in Mexico.HBV genotype H is predominant among the Mexican population,but not in Central America.Its geographic distribution is related to a typical endemicity among the Mexicans which is characterized by a low hepatitis B surface antigen seroprevalence,apparently due to a rapid resolution of the infection,low viral loads and a high prevalence of occult B infection.During chronic infections,genotype H is detected in mixtures with other HBV genotypes and associated with other co-morbidities,such as obesity,alcoholism and co-infection with hepatitis C virus or human immunodeficiency virus.Hepatocellular carcinoma prevalence is low.Thus,antiviral therapy may differ significantly from the standard guidelines established worldwide.The high prevalence of HBV genotype G in the Americas,especially among the Mexican population,raises new questions regarding its geographic origin that will require further investigation.     

Harnessing the potential of gene editing technology using CRISPR in inflammatory bowel disease

The molecular scalpel of clustered regularly interspersed short palindromic repeats/CRISPR associated protein 9(CRISPR/Cas9) technology may be sharp enough to begin cutting the genes implicated in inflammatory bowel disease(IBD) and consequently decrease the 6.3 billion dollar annual financial healthcare burden in the treatment of IBD. For the past few years CRISPR technology has drastically revolutionized DNA engineering and biomedical research field. We are beginning to see its application in gene manipulation of sickle cell disease,human immunodeficiency virus resistant embryologic twin gene modification and IBD genes such as Gatm(Glycine amidinotransferase, mitochondrial),nucleotide-binding oligomerization domain-containing protein 2, KRT12 and other genes implicated in adaptive immune convergence pathways have been subjected to gene editing, however there are very few publications. Furthermore,since Crohn's disease and ulcerative colitis have shared disease susceptibility and share genetic gene profile, it is paramount and is more advantageous to use CRISPR technology to maximize impact. Although, currently CRISPR does have its limitations due to limited number of specific Cas enzymes, off-target activity,protospacer adjacent motifs and crossfire between different target sites. However,these limitations have given researchers further insight on how to augment and manipulate enzymes to enable precise gene excision and limit crossfire between target sites.     

Abdominal compartment syndrome:Often overlooked conditions in medical intensive care units

Intra-abdominal hypertension(IAH)and abdominal compartment syndrome are well recognized entities among surgical patients.Nevertheless,a number of prospective and retrospective observational studies have shown that IAH is prevalent in about half of the critically ill patients in the medical intensive care units(ICU)and has been widely recognized as an independent risk factor for mortality.It is alarming to note that many members of the critical care team in medical ICU are not aware of the consequences of untreated IAH and the delay in making the diagnosis leads to increased morbidity and mortality.Frequently it is underdiagnosed and undertreated in this patient population.Elevated intraabdominal pressure decreases the blood flow to the kidneys and other abdominal viscera and also results in reduced cardiac output and difficulties in ventilating the patient because of increased intrathoracic pressure.When intraabdominal hypertension is not promptly recognized and treated,it leads to abdominal compartment syndrome,multiorgan dysfunction syndrome and death.Large volume fluid resuscitation is very common in medical ICU patients presenting with sepsis,shock and other inflammatory conditions like pancreatitis and it is one of the major risk factors for the development of intra-abdominal hypertension.This article presents an overview of the epidemiology,definitions,risk factors,pathophysiology and management of IAH and abdominal compartment syndrome in critically ill medical ICU patients.     

Current status of endoscopic retrograde cholangiopancreatography in patients with surgically altered anatomy

Endoscopic retrograde cholangiopancreatography(ERCP)in patients with surgically altered anatomy must be performed by a highly experienced endoscopist.The challenges are accessing the afferent limb in different types of reconstruction,cannulating a papilla with a reverse orientation,and performing therapeutic interventions with uncommon endoscopic accessories.The development of endoscopic techniques has led to higher success rates in this group of patients.Device-assisted ERCP is the endoscopic procedure of choice for high success rates in short-limb reconstruction;however,these success rate is lower in long-limb reconstruction.ERCP assisted by endoscopic ultrasonography is now popular because it can be performed independent of the limb length;however,it must be performed by a highly experienced and skilled endoscopist.Stent deployment and small stone removal can be performed immediately after ERCP assisted by endoscopic ultrasonography,but the second session is needed for other difficult procedures such as cholangioscopy-guided electrohydraulic lithotripsy.Laparoscopic-assisted ERCP has an almost 100%success rate in longlimb reconstruction because of the use of a conventional side-view duodenoscope,which is compatible with standard accessories.This requires cooperation between the surgeon and endoscopist and is suitable in urgent situations requiring concomitant cholecystectomy.This review focuses on the advantages,disadvantages,and outcomes of various procedures that are suitable in different situations and reconstruction types.Emerging new techniques and their outcomes are also discussed.     

Loss of BRCA1 expression leads to worse survival in patients with gastric carcinoma

AIM: To investigate the expression deficiency of key molecular markers in the homologous recombination pathway. METHODS: Expression loss of breast cancer type 1 susceptibility protein (BRCA1), ataxia telangiectasia mutated (ATM), ATM-Rad3-related (ATR), mediator of DNA damage checkpoint protein 1 (MDC1) and meiotic recombination 11 (Mre11) were correlated with their clinicopathological parameters in gastric cancer (GC). One hundred and twenty treatment-naive GC samples were formalin-fixed and paraffin-embedded into tissue blocks. Two representative cores from each block were extracted and constructed into tissue microarrays. Expression levels of BRCA1, ATM, ATR, MDC1 and Mre11 were determined using immunohistochemical analysis, and correlated with clinical parameters, including age, gender, Lauren subtype, tumor grades, clinical stage and overall survival.RESULTS: Expression loss of BRCA1, ATM, ATR, MDC1, and Mre11 was found in 21.4%, 20.2%, 21.0%, 11.1% and 4.6%, respectively, of interpretable cases. BRCA1 loss was significantly associated with patients of diffused subtype (intestinal vs diffused, 8.2% vs 31.7%, P = 0.001), higher tumor grade (Ⅰ/Ⅱ vs Ⅲ, 10.7% vs 20.5;Ⅰ/Ⅱ vs Ⅳ, 10.7% vs 54.5%, P = 0.047) and advanced clinical stage (Ⅰ/Ⅱ vs Ⅲ, 12.9% vs 16.9%;Ⅰ /Ⅱ vs Ⅳ, 12.9% vs 45.5%, P = 0.006). MDC1 loss was significantly associated with patients of diffused subtype (intestinal vs diffused, 0% vs 19.7%, P = 0.001) and higher tumor grade (Ⅰ/Ⅱ vs Ⅲ, 0% vs 12%;Ⅰ/Ⅱ vs Ⅳ, 0% vs 30.8%, P = 0.012). In addition, the survival time of the patients with expression loss of BRCA1 was significantly shorter than those with positive expression of BRCA1 (2-year survival rate, 32.4% vs 62.8%, P = 0.015). No correlations were found between clinicopathological parameters and expression loss of ATM, ATR and Mre11. CONCLUSION: Our results support the hypothesis that homologous recombination deficiency plays an important role in the progression of gastric carcinoma. Loss of expression of BRCA1 and     

Assessment of chronic radiation proctopathy and radiofrequency ablation treatment follow-up with optical coherence tomography angiography: A pilot study

BACKGROUND Chronic radiation proctopathy(CRP) occurs as a result of pelvic radiation therapy and is associated with formation of abnormal vasculature that may lead to persistent rectal bleeding. While incidence is declining due to refinement of radiation delivery techniques, CRP remains one of the major complications of pelvic radiation therapy and significantly affects patient quality of life.Radiofrequency ablation(RFA) is an emerging treatment modality for eradicating abnormal vasculature associated with CRP. However, questions remain regarding CRP pathophysiology and optimal disease management.AIM To study feasibility of optical coherence tomography angiography(OCTA) for investigating subsurface vascular alterations in CRP and response to RFA treatment.METHODS Two patients with normal rectum and 8 patients referred for, or undergoing endoscopic RFA treatment for CRP were imaged with a prototype ultrahighspeed optical coherence tomography(OCT) system over 15 OCT/colonoscopy visits(2 normal patients, 5 RFA-na?ve patients, 8 RFA-follow-up visits). OCT and OCTA was performed by placing the OCT catheter onto the dentate line and rectum without endoscopic guidance. OCTA enabled depth-resolved microvasculature imaging using motion contrast from flowing blood, withoutrequiring injected dyes. OCTA features of normal and abnormal microvasculature were assessed in the mucosa and submucosa. Blinded reading of OCTA images was performed to assess the association of abnormal rectal microvasculature with CRP and RFA treatment, and rectal telangiectasia density endoscopic scoring.RESULTS OCTA/OCT images are intrinsically co-registered and enabled depth-resolved visualization of microvasculature in the mucosa and submucosa. OCTA visualized normal vascular patterns with regular honeycomb patterns vs abnormal vasculature with distorted honeycomb patterns and ectatic/tortuous microvasculature in the rectal mucosa. Normal arterioles and venules < 200 μm in diameter versus abnormal heterogenous enlarged arterioles and venules > 200μm in diameter were visualized in the rectal submucosa. Abnormal mucosal vasculature occurred in 0 of 2 normal patients and 3 of 5 RFA-na?ve patients,while abnormal submucosal vasculature occurred more often, in 1 of 2 normal patients and 5 of 5 RFA-na?ve patients. After RFA treatment, vascular abnormalities decreased, with abnormal mucosal vasculature observed in 0 of 8 RFA-follow-up visits and abnormal submucosal vasculature observed in only and 2 of 8 RFA-follow-up visits.CONCLUSION OCTA visualizes depth-resolved microvascular abnormalities in CRP, allowing assessment of superficial features which are endoscopically visible as well as deeper vasculature which cannot be seen endoscopically. OCTA/OCT of the rectum can be performed in conjunction with, or independently from endoscopy.Further studies are warranted to investigate if OCTA/OCT can elucidate pathophysiology of CRP or improve management.     

Hepatoprotective actions of melatonin: possible mediation by melatonin receptors

Melatonin,the hormone of darkness and messenger of the photoperiod,is also well known to exhibit strong direct and indirect antioxidant properties. Melatonin has previously been demonstrated to be a powerful organ protective substance in numerous models of injury; these beneficial effects have been attributed to the hormone’s intense radical scavenging capacity. The present report reviews the hepatoprotective potential of the pineal hormone in various models of oxidative stress in vivo,and summarizes the extensive literature showing that melatonin may be a suitable experimental substance to reduce liver damage after sepsis,hemorrhagic shock,ischemia/reperfusion,and in numerous models of toxic liver injury. Melatonin’s influence on hepatic antioxidant enzymes and other potentially relevant pathways,such as nitric oxide signaling,hepatic cytokine and heat shock protein expression,are evaluated. Based on recent literature demonstrating the functional relevance of melatonin receptor activation for hepatic organ protection,this article finally suggests that melatonin receptors could mediate the hepatoprotective actions of melatonin therapy.     

Separate calculation of DW-MRI in assessing therapeutic effect in liver tumors in rats

AIM:To explore whether the antitumor effect of a vascular disrupting agent(VDA)would be enhanced by combining with an antiangiogenic agent,and whether such synergistic effects can be effectively evaluated with separate calculation of diffusion weighted magnetic resonance imaging(DW-MRI).METHODS:Thirty-seven rats with implanted liver tumors were randomized into the following three groups:(1)ZD6126,a kind of VDA;(2)ZDTHA,ZD6126 in combination with an antiangiogenic,thalidomide;and(3)control.Morphological DW-MRI were performed and quantified before,4 h and 2 d after treatment.The apparent diffusion coefficient(ADC)values were calculated separately for low b values(ADC low),high b values(ADC high)and all b values(ADC all).The tissue perfusion contribution,ADC perf,was calculated as ADC low-ADC high.Imaging findings were finally verified by histopathology.RESULTS:The combination therapy with ZDTHA significantly delayed tumor growth due to synergistic effects by inducing cumulative tumor necrosis.In addition to delaying tumor growth,ZDTHA caused tumor necrosis in an additive manner,which was verified by HE staining.Although both ADC high and ADC all in the ZD6126and ZDTHA groups were significantly higher compared to those in the control group on day 2,the entire tumor ADC high of ZDTHA was even higher than that of ZD6126,but the significant difference was not observed for ADCall between ZDTHA and ZD6126.This indicated that the perfusion insensitive ADC high values calculated from high b value images performed significantly better than ADC all for the monitoring of tumor necrosis on day 2.The perfusion sensitive ADC perf derived from ADC low by excluding high b value effects could better reflect the reduction of blood flow due to the vessel shutdown induced by ZD6126,compared to the ADC low at 4 h.The ADC perf could provide valuable perfusion information from DW-MRI data.CONCLUSION:The separate calculation of ADC is more useful than conventional averaged ADC in evaluating the efficacy of combination therapy with ZD6126     

Interleukin-1β gene polymorphism associated with hepatocellular carcinoma in hepatitis B virus infection

AIM: To examine the effect of interleukin-1-beta (IL-1β)promoter region C-511T and IL-1 receptor antagonist (IL-1RN) polymorphism among the patients with chronic hepatitis B virus (HBV) infection (HCC and non-HCC).METHODS: Genomic DNA from 136 Thai patients with chronic HBV infection (HCC=46 and non-HCC=90) and 152 healthy individuals was genotyped for IL-1β gene polymorphism (-511) using polymerase chain reaction with sequence specific primers (PCR-SSP). The variable number of tandem repeats (VNTR) of IL-1RN gene was assessed by a PCR-based assay. The association between these genes and status of the disease was evaluated by X2 test.RESULTS: IL-1B-511 genotype C/C was found to be significantly different in patients with HCC when compared with healthy individuals (P = 0.036, OR = 2.29,95%CI = 1.05-4.97) and patients without HCC (P=0.036,OR=2.52, 95%CI=1.05-6.04). Analysis of allele frequencies of IL-1B-511 showed that IL-1B-511 C allele was also significantly increased in patients with HCC, compared to that in healthy control (P=0.033,OR= 1.72, 95%CI=1.04-2.84). However, no significant association in IL-1RN gene was found between the two groups.CONCLUSION: IL-1B-511C allele, which may be associated with high IL-1B production in the liver, is a genetic marker for the development of HCC in chronic hepatitis B patients in Thai population.     

Association between interleukin-1 gene polymorphisms and Helicobacter pylori infection in gastric carcinogenesis in a Chinese population

BACKGROUND AND AIM: Helicobacter pylori is a major cause of chronic gastritis and peptic ulcer disease and a definite carcinogen for gastric adenocarcinoma. However, the underlying pathogenic mechanisms are not fully understood. Interleukin-1 (IL-1) is a key cytokine involved in H. pylori-induced gastric inflammation. The present study aimed to determine polymorphisms of IL-1B and IL-1 receptor antagonist (IL-1RN) genes and their association with H. pylori infection and gastroduodenal diseases in Chinese patients. METHODS: Three hundred and ninety-nine patients with gastroduodenal diseases (129 chronic gastritis, 127 duodenal ulcer and 143 non-cardiac gastric cancer) and 264 healthy controls were genotyped for IL-1B-511 and IL-1RN gene polymorphisms by the PCR-RFLP method. H. pylori infection status was determined by a validated serological test. RESULTS: The frequency of IL-1B-511 T allele was significantly higher in H. pylori positive patients with non-cardiac gastric cancer than in both H. pylori negative patients with non-cardiac gastric cancer (60%vs 46%, P = 0.0342, OR = 1.666, 95% confidence interval [CI]: 1.045-2.656) and in healthy controls (60%vs 48%, P = 0.0071, OR = 1.665, 95%CI: 1.149-2.412). However, the polymorphism was not associated with chronic gastritis and duodenal ulcer. Multivariate logistic regression analyses identified that IL-1B-511 T/T carrier status was an independent risk factor for non-cardiac gastric cancer in the presence of H. pylori infection (adjusted OR = 3.01, 95%CI: 1.27-7.11, P = 0.01), and the frequency of IL-1B-511 T allele was an increased risk factor for developing gastric cancer (P = 0.03, adjusted OR = 2.29, 95%CI: 1.08-4.86). There was no association between IL-1RN gene polymorphisms and H. pylori infection and other gastroduodenal diseases. CONCLUSION: IL-1B-511 T allele is associated with H. pylori infection in non-cardiac gastric cancer in a Chinese population. The IL-1B-511 gene polymorphism appears to play an important role in gastric carcinogenesis in Chinese patients with H. pylori infection.     

Interleukin-21 gene polymorphisms and chronic hepatitis B infection in a Chinese population

AIM: To investigate the relationship between inter-leukin-21(IL21) gene polymorphisms and chronic hepatitis B virus(HBV) infection in a Chinese population. METHODS: In this case-control study, 366 Chinese HBV-infected patients were recruited and divided into hepatocellular carcinoma(HCC; n = 94) and non-HCC(n = 272) groups at The First Affiliated Hospital of Sun Yat-Sen University, from April 2009 to December 2012. In the non-HCC group, the patients were classified into three clinical subsets, 76 patients had chronic hepatitis B, 101 were HBV carriers and 95 patients had HBV-related cirrhosis. Two hundred eight unrelated healthy controls were also included. Genomic DNA was extracted from peripheral blood. Single nucleotide polymorphisms(SNPs) rs13143866, rs2221903, and rs907715 were subsequently genotyped using the SNaP shot SNP technique.RESULTS: There were no significant differences in allele and genotype frequencies of SNPs rs13143866, rs2221903, and rs907715 between chronic HBVinfected patients and control subjects. Furthermore, no significant differences were found in the frequencies of all alleles and genotypes between the HCC group and the non-HCC group. However, in the subgroup analysis, IL21 rs13143866 genotype AA frequency in the HBV carrier group was higher than in controls(OR = 6.280, 95%CI: 1.238-31.854; P = 0.019), and the effect of the recessive model(AA vs GG + GA, OR = 6.505, 95%CI: 1.289-32.828) was observed in the HBV carrier group. IL21 rs2221903 genotype TC frequency in the HBV carrier group was higher than in controls(OR = 1.809, 95%CI: 1.043-3.139; P = 0.035). In the haplotype analysis, the ATA haplotype(rs13143866, rs2221903, and rs907715) of IL21 was more frequent in the HCC group than in the non-HCC group(0.165 vs 0.104, P = 0.044; OR = 1.700, 95%CI: 1.010-2.863).CONCLUSION: Genotypes rs13143866 AA and rs2221903 TC are risk factors for carrying HBV; ATA haplotype increases the risk of HBV-related HCC onsetin a Chinese population.     

汉族人群乙型肝炎病毒感染者外周血IL-28B基因多态性研究*

目的 分析乙型肝炎病毒（HBV）感染者外周血IL-28B基因型和等位基因频率分布,并探讨其与疾病病程和进展的关系。方法 本研究纳入江苏籍汉族健康人群145例和453例HBV感染者,后者包括无症状HBV携带者（ASC）45例,慢性乙型肝炎患者（CHB）181例,肝硬化（LC）患者69例,肝细胞癌（HCC）患者79例,乙型肝炎肝衰竭（LF）患者79例,采用PCR法和直接测序法检测外周血IL-28B基因rs12979860和rs8099917多态性位点。采用Pearson x²检验对IL-28B rs8099917与rs12979860位点进行Hardy-Weinberg平衡检验,计量资料以（x±s）表示,计数资料采用例数表示。应用SPSS 17.0软件进行方差分析、x²检验和Binary Logistic回归分析。结果 IL-28B基因rs12979860位点有CC、CT和TT 3个基因型,LF患者CC型和C等位基因频率分别为96.2%和98.1%,显著高于健康人群的87.6%和93.1%（OR=0.257,95%CI=0.068~0.973,P=0.045;OR=0.255,95%CI=0.070~0.928,P=0.038）;IL-28B基因rs8099917位点有TT 、TG和GG 3个基因型,LC患者TT型和T等位基因频率分别为92.8%和96.4%,显著高于健康人群的86.2%和92.4%（OR=0.288,95%CI=0.087~0.948,P=0.041;OR=0.299,95%CI=0.096~0.926,P=0.036）。结论 江苏地区汉族人群IL-28B基因多态性与HBV感染后不同疾病表型相关,IL-28B基因rs12979860的C等位基因和IL-28B基因rs8099917的T等位基因可能是HBV感染后病情进展的影响因素。     

Association between polymorphisms of the APOBEC3G gene and chronic hepatitis B viral infection and hepatitis B virusrelated hepatocellular carcinoma

AIM to determine the relationship between five A3 G gene single nucleotide polymorphisms and the incidence of hepatitis B virus(HBV) infection and hepatocellular carcinoma(HCC). METHODS this association study was designed as a retrospective study, including 657 patients with chronic HBV infection(CHB) and 299 healthy controls. All subjects were ethnic Han Chinese. Chronic HBV-infected patients recruited between 2012 and 2015 at the First Hospital of Jilin University(Changchun) were further classified into HBV-related HCC patients(n = 287) and non-HCC patients(n = 370). Frequency matching by age and sex was performed for each group. Human genomic DNAwas extracted from whole blood. Gene polymorphisms were identified using a mass spectroscopic method.RESULTS there were no significant differences between the genotype and allele frequencies of the rs7291971, rs5757465 and rs5757463 A3 G gene polymorphisms, and risk of CHB and HBV-related HCC. the AG genotype and G allele for rs8177832 were significantly related to a decreased risk of CHB(OR = 0.67, 95%CI: 0.47-0.96; OR = 0.69, 95%CI: 0.50-0.95, respectively) and HCC(OR = 0.53, 95%CI: 0.34-0.84; OR = 0.58, 95%CI: 0.39-0.87, respectively). A significant relationship was found between rs2011861 computed tomography, tt genotypes and increased risk of HCC(OR = 1.69, 95%CI: 1.02-2.80; OR = 1.82, 95%CI: 1.08-3.06, respectively). Haplotype analyses showed three protective and four risk haplotypes for HCC. Also, one protective haplotype was found against CHB.CONCLUSION this study indicates that the A3 G rs8177832 polymorphism is associated with a decreased risk of CHB infection and HCC, while the rs2011861 polymorphism is associated with an increased risk of HCC.     

Impact of interleukin-1beta genetic polymorphisms on the development of hepatitis C virus-related hepatocellular carcinoma in Japan

To examine the effects of polymorphisms in the gene encoding proinflammatory interleukin (IL)-1beta in patients infected with hepatitis C virus (HCV) in Japan, we studied 364 patients with chronic HCV infection (146 of whom had hepatocellular carcinoma [HCC] and 218 of whom did not) and 230 healthy control subjects. IL-1B-511 and IL-1RN genotypes were ascertained, and IL-1B-511 genotype T/T was found to be significant risk factors for the development of HCC, indicating that polymorphism in the IL-1B-511 genetic locus is one of the possible determinants of progression of hepatitis C to HCC.     

Association of HLA-DRB1*13 and TNF-alpha gene polymorphisms with clearance of chronic hepatitis B infection and risk of hepatocellular carcinoma in Thai population

Considerable evidence suggests that host genetic factor play an important role in the pathogenesis and clinical outcome of chronic hepatitis B virus (HBV) infection in several ethic groups. Association study was performed included 150 chronic HBV patients, 100 resolved hepatitis B and 150 healthy individuals with similar ethic background. Interestingly, human leucocyte antigen (HLA)-DR13 show a strong association with the clearance of HBV [odds ratio (OR) = 0.04, 95% confidence interval (CI) = 0.00-0.26, corrected P-value (P(c)) = 0.0008] similar to reports from several ethic groups. TNF-alpha promoter polymorphisms (-863, -308 and -238) were also analysed. Only -863 C allele was found to be significantly decreased in chronic HBV patients compared with healthy control (P(c) = 0.03, OR = 0.54, 95% CI = 0.35-0.84 respectively). This -863C allele was not in linkage disequilibrium with HLA-DR13 suggesting that other genetic markers linked with -863C might influence clearance of chronic HBV infection in Thai. When stratified chronic HBV patients into patients without hepatocellular carcinoma (HCC) and with HCC, the -863 A allele was significantly increased in the HCC group compared to healthy control (P(c) = 0.003, OR = 2.61, 95% CI = 1.49-4.60). Haplotype analysis (-863/-308/-238) revealed that the homozygosity of the haplotype (CGG/CGG) was a protective marker for HCC (OR = 0.37, 95% CI = 0.17-0.79, P(c) = 0.02). One can propose that carriers of -863A genotype are associated with increased levels of TNF-alpha in the liver in response to HBV infection and induce hapatocyte damage that may finally lead to HCC development. Additional study is needed to validate these finding and to further explore the genetic pathogenesis of HBV infection.     

Polymorphism in IL1B: IL1B-511 association with tuberculosis and decreased lipopolysaccharide-induced IL-1beta in IFN-gamma primed ex-vivo whole blood assay

To determine whether variation in two interleukin 1 family genes (IL1B and interleukin 1 receptor antagonist, IL1RN) is associated with pulmonary tuberculosis (TB), two published polymorphisms at nucleotide positions -511 and +3953 in IL1B and one in the IL1RN 86 bp VNTR were genotyped in 335 smear positive Gambian TB patients, and 298 ethnically matched controls. All individuals were HIV negative. Decreased risk of pulmonary TB was associated with both heterozygosity and homozygosity for the IL1B-511-C allele (OR 0.66, P = 0.027, and OR 0.58, P = 0.015, respectively). Nonetheless, the C allele was present at a frequency of 0.66 in TB cases suggesting that whilst IL-1beta contributes to disease susceptibility, it is not the major factor. There was no association between the IL1B+3953-T/C polymorphism or the 86 bp IL1RN pentallelic repeat and TB in this population. Using an ex-vivo whole blood assay, healthy Gambian individuals who are homozygous for the IL1B-511-T allele failed to exhibit a significant increase in IL-1beta production in response to LPS after IFN-gamma priming.     

Interleukin-1beta and interleukin-1 receptor antagonist gene polymorphisms in ankylosing spondylitis

OBJECTIVE: Since ulcerative colitis and Crohn's disease, which are associated with ankylosing spondylitis (AS), have been found to be variably associated with the IL-1B and the IL-1RN genes encoding interleukin-1beta (IL-1beta) and the interleukin-1 receptor antagonist (IL-1ra), we have investigated whether these polymorphisms in IL-1B and IL-1RN are also involved in AS. METHODS: DNA was isolated from peripheral blood of 106 patients with AS and 104 healthy controls. All patients and controls were Dutch Caucasians. Bi-allelic polymorphisms at positions +3,953 and -511 in the IL-1B gene, and a penta-allelic polymorphism in intron 2 of the IL-1RN gene were studied by polymerase chain reaction-based methods. RESULTS: Allele IL-1RN*2 was significantly increased in AS (odds ratio=1.60; 95% confidence interval=1.20-2.80; P=0.031) compared with healthy controls, and independent from the polymorphism in loci IL-1B-511 and IL-1B+3,953. No significant associations were found between AS and the IL-1B-511 or IL-1B+3,953 polymorphisms. CONCLUSION: Similar to other chronic inflammatory diseases, AS is associated with the IL-1RN*2 allele. Further studies are necessary to determine the biological significance of these findings in relation to susceptibility or severity of the disease.     

白细胞介素-1基因多态性与消化性溃疡的关系

背景：大量临床流行病学证据表明消化性溃疡发病率的地域差异与宿主免疫遗传因素密切相关,目前宿主炎症因子基因多态性与消化性溃疡的关系正受到广泛关注。目的：探讨白细胞介素（IL）-1B-511、IL-1RN基因多态性与消化性溃疡的关系。方法：选取2008年9月～2009年5月昆明医学院第一附属医院确诊的57例十二指肠溃疡（DU）、38例胃溃疡（GU）以及40例非萎缩性胃炎（NAG）患者。以快速尿素酶试验和Giemsa染色检测幽门螺杆菌（H.pylori）感染,采用PCR-RFLP检测IL-1B-511、IL-1RN基因多态性。分析IL-1基因多态性、H.pylori感染、年龄与不同疾病之间的关系。结果：NAG、DU和GU组之间H.pylori感染率、IL-1B-511、IL-1RN基因型频率的差异无统计学意义。与NAG和DU相比,年龄≥60岁是GU的危险因素（OR=5.650,95%CI：1.811～17.624;OR=3.159,95%CI：1.254～7.955）。IL-1B-511、IL-1RN基因型和H.pylori感染与消化性溃疡类型无关（P〉0.05）。结论：在昆明市,年龄≥60岁是GU的危险因素,IL-1基因多态性与消化性溃疡无关。