力学刺激通过YAP信号调控炎症牙周膜铁死亡的作用与机制研究

目的本研究旨在探究力学刺激下牙周炎牙周膜铁死亡的变化,以及该过程中YAP的作用及可能机制。方法通过炎症因子TNFα(10 ng/m L)和IL-1β(5 ng/m L)诱导建立牙周膜成纤维细胞体外炎症模型,根据是否进行加力(3 h,0~120 k Pa,0.1 Hz)处理分为对照组、炎症组、加力组、炎症+加力组;进行CCK8检测细胞增殖、划痕实验检测细胞迁移;通过检测Fe^(2+)含量、流式细胞术检测ROS含量、WB检测铁死亡相关分子ACSL4相对表达水平,分析铁死亡水平;通过免疫荧光以及WB检测YAP相对表达水平。结果与对照组和加力组相比,炎症组及炎症+加力组细胞增殖、迁移速率变慢;Fe^(2+)及ROS含量升高,WB检测显示ACSL4含量升高,铁死亡水平升高,其中炎症+加力组细胞铁死亡升高更明显。与对照组及炎症组相比,加力组及炎症+加力组WB检测显示YAP磷酸化水平降低。免疫荧光染色显示与对照组相比,加力组、炎症组及炎症+加力组荧光强度核浆比更高。结论力学刺激促进牙周炎牙周膜细胞YAP核易位,在细胞核内参与ACSL4等基因转录,调控铁死亡发生,影响牙周膜细胞增殖、迁移等生物学特性,参与牙周炎发展进程。

胃癌核仁组成区相关蛋白的研究

本研究应用核仁组成区相关嗜银蛋白(AgNOR染色技术,在光镜及电镜下观察了37例胃粘膜活检标本。光镜定量观察显示,不典型增生及胃癌(高分化与低分化)上皮AgNOR数目,均显著多于正常和炎症病变上皮;胃癌组AgNOR均值还显著高于不典型增生组,但两组中AgNOR数值有一定程度的重叠。电镜观察见AgNOR颗粒位于细胞核仁区,胃癌上皮AgNOR颗粒排列分散,散布于整个核仁区;而正常胃粘膜上皮AgNOR颗粒分布集中。本研究结果提示,胃粘膜上皮AgNOR数目及形态的表现,对于胃良、恶性病变的判断有极大的帮助。

Twist和YB-1蛋白在宫颈鳞状细胞癌中的表达与临床意义

宫颈癌是女性生殖系统最常见的恶性肿瘤之一,其发生率和病死率在女性恶性肿瘤仅次于乳腺癌。近年来研究发现,女性患者长期感染高危型人乳头瘤病毒（HPVs）后,一部分患者会发展为宫颈上皮内瘤变（CIN）,并由CIN发展为癌,但并非所有的CIN均发展为癌,从CIN发展为宫颈癌需经历较长时间,这是一个复杂的多步骤癌变过程。

108例肺不张纤维支气管镜检查结果分析

肺不张不是一个独立的疾病,而是多种胸部疾病的并发症。因此,不仅能满足于作出此诊断,而应力求明确其病因。我院自1986年1月～1992年6月,对临床已排除肺结核的108例肺不张病人行纤维支气管镜(简称纤支镜)检查,结果分析如下。

C反应蛋白在几种妇科疾病中的含量变化

C反应蛋白(CRP)是一种急性时相反应蛋白,在各种急慢性感染或组织损伤时都可能使其浓度升高[1,2]。我们对子宫附件炎等多种妇科疾病患者进行了CRP连续监测,以探讨CRP在各种妇科疾病如急性盆腔炎、宫外孕、急性流产等的诊断与鉴别诊断中的参考价值。

世界小动物兽医师协会——每月新闻

2008年2月WSAVA活动与理事会报告WSAVAGI标准化工作小组WSAVAGI标准化工作小组在2007年的ECVIH(欧洲兽医内科专科医学会)大会中,在匈牙利首部布达佩斯召开了会议,对未来3至12个月即将进行的几项计划进行了部署。

An unusual cause of cholecystitis:Heterotopic pancreatic tissue in the gallbladder

Gallbladder localization of heterotopic pancreas （HP） is uncommon and very rarely gives rise to symptoms. Herein we report a case of HP found in the gallbladder neck presented with signs and symptoms of cholecystitis. The patient was a 40-year old male, suffering from epigastric pain, abdominal fullness and fever. On physical examination, the right upper abdomen was tender with a positive Murphy＇s sign. Ultrasonographic examination showed a hydropic gallbladder without stones and he underwent a cholecystectomy. Pathological examination revealed an intramural nodule （9 ram） in the neck region which is consisted of acini, ducts and islet cells of an aberrant pancreatic tissue. Although HP is encountered rarely in the gallbladder and is found incidentally during pathological studies, this case emphasizes that HP might cause symptoms and present clinically as cholecystitis. For this reason, in patients presenting with symptomatic gallbladder diseases, including cholecystitis without any other pathology, HP should be taken into consideration before it is diagnosed as ＂idiopathic＇：

Effects of Buddlejae Flos Granules on Inflammatory Factors TGF-β1,NF-κB,IL-10 and IL-12 in Lacrimal Gland Cells of Castrated Male Rabbits

Objective To observe the effects of Buddlejae Flos (Mi Meng Hua,密蒙花) granules on the expression of TGF-β1, NF-κB, IL-10 and IL-12 in lacrimal gland cells in castrated male rabbits. Methods A total of 30 New Zealand male white rabbits were randomly divided into 5 groups. Group A: blank group;group B: model group;group C: Buddlejae Flos (Mi Meng Hua,密蒙花) granules group;group D: placebo group;group E: testosterone group. Except for the group A, all rabbits were treated with bilateral testicular and epididymis resection before intervention. Rabbits in group C were administered with Buddlejae Flos (Mi Meng Hua,密蒙花) granules (100 mg/kg), 3 times per day;Rabbits in group D were administered with normal saline, 3 times per day. Rabbits in group E were injected with testosterone propionate (0.5 mL/kg) in the thigh muscle, every 3 days. Schirmer I test (SIT) and break-up time (BUT) were measured on 1st day before modeling and 30th day after modeling. After 30 days of intervention, all rabbits were sacrificed. The removal lacrimal gland was stained in immunohistochemica staining. The expression of TGF-β1, NF-κB, IL-10 and IL-12 in lacrimal gland tissue of each group was detected, and the structure of lacrimal gland was observed. Results The results of SIT and BUT showed that there was significant difference between group B and D compared with group A (P < 0.05). There were no significant differences between group C and E (P > 0.05). There were no significant differences in the comparison of inflammatory factors TGF-β1, NF-κB, IL-10 and IL-12 between group B and D (P > 0.05). There were significant differences between group B and D compared with other groups (P < 0.01). There was no significant difference between group A, C and E (P > 0.05). Conclusions Buddlejae Flos (Mi Meng Hua,密蒙花) granules have an inhibitory effect on the expression of TGF-β1, NF-κB, IL-10 and IL-12 in castrated male rabbit lacrimal gland cells, and alleviate the inflammation of lacrimal gland tissue by inhibiting the expression of TGF-β1, NF-κB, IL-10 and IL-12 in lacrimal gland tissue, so as to treat dry eye.

Molecular mechMolecular mechanism of glucocorticoid resistance in inflammatory bowel disease

Natural and synthetic glucocorticoids (GCs) are widely employed in a number of inflammatory, autoimmune and neoplastic diseases, and, despite the introduction of novel therapies, remain the first-line treatment for inducing remission in moderate to severe active Crohn’s disease and ulcerative colitis. Despite their extensive therapeutic use and the proven effectiveness, considerable clinical evidence of wide inter-individual differences in GC efficacy among patients has been reported, in particular when these agents are used in inflammatory diseases. In recent years, a detailed knowledge of the GC mechanism of action and of the genetic variants affecting GC activity at the molecular level has arisen from several studies. GCs interact with their cytoplasmic receptor, and are able to repress inflammatory gene expression through several distinct mechanisms. The glucocorticoid receptor (GR) is therefore crucial for the effects of these agents: mutations in the GR gene (NR3C1, nuclear receptor subfamily 3, group C, member 1) are the primary cause of a rare, inherited form of GC resistance; in addition, several polymorphisms of this gene have been described and associated with GC response and toxicity.However, the GR is not self-standing in the cell and the receptor-mediated functions are the result of a complex interplay of GR and many other cellular partners. The latter comprise several chaperonins of the large cooperative hetero-oligomeric complex that binds the hormonefree GR in the cytosol, and several factors involved in the transcriptional machinery and chromatin remodeling, that are critical for the hormonal control of target genes transcription in the nucleus. Furthermore, variants in the principal effectors of GCs (e.g. cytokines and their regulators) have also to be taken into account for a comprehensive evaluation of the variability in GC response. Polymorphisms in genes involved in the transport and/or metabolism of these hormones have also been suggested as other possible candidates of interest that could play a role in the observed inter-individual differences in efficacy and toxicity. The best-characterized example is the drug efflux pump P-glycoprotein, a membrane transporter that extrudes GCs from cells, thereby lowering their intracellular concentration. This protein is encoded by the ABCB1/ MDR1 gene; this gene presents different known polymorphic sites that can influence its expression and function. This editorial reviews the current knowledge on this topic and underlines the role of genetics in predicting GC clinical response. The ambitious goal of pharmacogenomic studies is to adapt therapies to a patient’s specific genetic background, thus improving on efficacy and safety rates.

Autofluorescence imaging endoscopy for identifi cation and assessment of inflammatory ulcerative colitis

AIM:To validate the clinical relevance of autofluores-cence imaging(AFI)endoscopy for the assessment of inflammatory ulcerative colitis(UC).METHODS:A total of 572 endoscopic images were se-lected from 42 UC patients:286 taken with white light imaging(WLI)and 286 with AFI from the same sites.WLI images were assessed for overall mucosal inflammation according to Mayo endoscopic subscore(MES),and for seven characteristic endoscopic features.Likewise,AFI photographs were scored according to relative abundance of red,green and blue color com-ponents within each image based on an RGB additive color model.WLI and AFI endoscopic scores from the same sites were compared.Histological evaluation of biopsies was according to the Riley Index.RESULTS:Relative to red(r=0.52,P<0.01)or blue(r=0.56,P<0.01)color component,the green color component of AFI(r=-0.62,P<0.01)corresponded more closely with mucosal inflammation sites.There were signif icant differences in green color components between MES-0(0.396±0.043)and MES-1(0.340± 0.035)(P<0.01),and between MES-1 and ≥ MES-2(0.318±0.037)(P<0.01).The WLI scores for "vascu-lar patterns"(r=-0.65,P<0.01),"edema"(r=-0.62,P<0.01),histology scores for "polymorphonuclear cells in the lamina propria"(r=-0.51,P<0.01)and "crypt architectural irregularities"(r=-0.51,P<0.01)showed correlation with the green color component of AFI.There were significant differences in green color components between limited(0.399± 0.042)and extensive(0.375±0.044)(P=0.014)polymorpho-nuclear cell inf iltration within MES-0.As the severity of the mucosal inflammation increased,the green color component of AFI decreased.The AFI green color com-ponent was well correlated with the characteristic en-doscopic and histological inflammatory features of UC.CONCLUSION:AFI has application in detecting inflammatory lesions,including microscopic activity in the co-lonic mucosa of UC patients,based on the green color component of images.

Construction and characterization of a cDNA library from human liver tissue with chronic hepatitis B

Objective: To construct a cDNA library from human liver tissue with chronic hepatitis B and check its quality for investigating the expression level of liver tissue infected by hepatitis B virus. This will then be used to find the relevant genes and interesting proteins associated with the development of hepatitis B. Methods: The total RNA from liver tissue with chronic hepa- titis B was extracted and the mRNA was purified using TRIZOL method. Switching mechanism at 5′ end of the RNA transcript (SMART) technique and CDS III/3′ primer were used for first-strand cDNA synthesis. Long distance polymerase chain reaction (LD PCR) was then used to synthesize the double-strand cDNA that was then digested by Sfi I and fractionated by CHROMA SPIN-400 column. The longer than 0.4 kb cDNAs were collected and ligated to λTriplEx2 vector. Then λ phage packaging reaction and library amplification were performed. The qualities of both unamplified and amplified cDNA libraries were strictly checked by conventional titer determination. Fourteen plaques were randomly picked and tested using PCR with universal primers derived from the sequence flanking the vector. Results: The titers of unamplifed and amplified libraries were 1.94×106 pfu/ml and 1.49×109 pfu/ml respectively. The percentages of recombinants from both libraries were 98.15% in unamplified library and 98.76% in amplified library. The lengths of the inserts were 1.23 kb in average, 1?2 kb in 64.29%, and 0.5?1.0 kb in 35.71%. Conclusion: A high quality cDNA library from human liver tissue with chronic hepatitis B was successfully constructed.

A rabbit model of pediatric nonalcoholic steatohepatitis: The role of adiponectin

AIM： To create a rabbit model of pediatric nonalcoholic steatohepatitis （NASH） and to evaluate the role of adiponectin in the process. METHODS： Thirty-two specific pathogen-free male New Zealand rabbits were divided randomly into three groups： （1） the normal control group （n = 10） was fed with standard diet for 12 wk; （2） the model group A （n = 11）; and （3） model group B （n = 11） were fed with a highfat diet （standard diet ＋ 10% lard ＋ 2% cholesterol） for 8 and 12 wk, respectively. Hepatic histological changes were observed and biochemical parameters as well as serum levels of adiponectin, interleukin （IL）-6, IL-10 and tumor necrosis factor （TNF）-α were measured. RESULTS： Typical histological hepatic lesions of NASH were observed in both model groups described as liver steatosis, liver inflammatory infiltration, cytologic ballooning, perisinusoidal fibrosis and overall fibrosis. Compared with the normal control group, there were significant increases in model groups A and B in weight gain （1097.2 ± 72.3, 1360.5± 107.6 vs 928.0 ±58.1, P 〈 0.05, P 〈 0.01）, liver weight （93.81±6.64, 104.6±4.42 vs 54.4±1.71, P 〈 0.01）, Lg （ALT） （1.9±0.29, 1.84± 0.28 vs 1.60±0.17, P 〈 0.01）, and Lg （TG） （1.03 ±0.24, 1.16 ±0.33 vs 0.00 ±0.16, P 〈 0.01）. Weight gain was much more in model group B than in model group A （1360.5± 107.6 vs 1097.2 ±72.3, P 〈 0.05）. But, there was no significant difference between the two groups concerning the other indexes. Pro-inflammatory cytokines （IL-6 and TNF-α） increased in model group B compared with that of control and model group A （IL-6：1.86±0.21 vs 1.41 ±0.33, 1.38± 0.42, P 〈 0.01; TNF-α： 1.18±0.07 vs 0.66 ±0.08, 0.86 ±0.43, P 〈 0.01, P 〈 0.05）, whereas serum adiponectin and IL-10 decreased in model groups compared with that in the control （adiponectin： A： 21.87±4.84 and B： 21.48 ±4.60 vs 27.36 ±7.29, P 〈 0.05. IL-10： A： 1.72± 0.38 and B： 1.83 ±0.39 vs 2.26±0.24, P 〈 0.01）. Lg （TC） and the degree of liver fatty infiltration was an independent determinant of serum adiponectin level analyzed by stepwise multiple regressions, resulting in 29.4% of variances. CONCLUSION： This rabbit model produces the key features of pediatric NASH and may provide a realistic model for future studies. Adiponectin level partially reflects the severity of liver steatosis, but not the degree of liver inflammation.

Acute pancreatitis at the beginning of the 21st century: The state of the art

Acute pancreatitis is an acute inflammatory disease of the pancreas which can lead to a systemic inflammatory response syndrome with significant morbidity and mortality in 20% of patients. Gallstones and alcohol consumption are the most frequent causes of pancreatitis in adults. The treatment of mild acute pancreatitis is conservative and supportive; however severe episodes characterized by necrosis of the pancreatic tissue may require surgical intervention. Advanced understanding of the pathology, and increased interest in assessment of disease severity are the cornerstones of future management strategies of this complex and heterogeneous disease in the 21st century.

Innate and adaptive immunity in inflammatory bowel disease

Inflammatory bowel diseases are the consequence of a dysregulated mucosal immune system. The mucosal immune system consists of two arms, innate and adaptive immunity, that have been studied separately for a long time. Functional studies from in vivo models of intestinal inflammation as well as results from genome-wide association studies strongly suggest a crossregulation of both arms. The present review will illustrate this interaction by selecting examples from innate immunity and adaptive immunity, and their direct impact on each other. Broadening our view by focusing on the cross-regulated areas of the mucosal immune system will not only facilitate our understanding of disease, but furthermore will allow identification of future therapeutic targets.

An epidemiological study of collagenous colitis in southern Sweden from 2001-2010

AIM： To estimate the incidence of collagenous colitis （CC） in southern Sweden during 2001-2010. METHODS： Cases were identified by searching for CC in the diagnostic registers at the Pathology Departments in the county of Skane. The catchment area comprised the south-west part of the county （394 307 inhabitants in 2010） and is a mixed urban and rural type with limited migration. CC patients that had under- gone colonoscopy during the defined period and were living in this area were included in the study regardless of where in Skane they had been diagnosed. Medical records were scrutinized and uncertain cases were re- assessed to ensure that only newly diagnosed CC cases were included. The diagnosis of CC was based on both clinical and histopathological criteria. The clinical crite-rion was non-bloody watery diarrhoea. The histopatho- logical criteria were a chronic inflammatory infiltrate in the lamina propria, a thickened subepithelial collagen layer ≥10 micrometers （um） and epithelial damage such as flattening and detachment. RESULTS： During the ten year period from 2001-2010, 198 CC patients in the south-west part of the county of Skane in southern Sweden were newly diagnosed. Of these, 146 were women and 52 were men, i.e., a female： male ratio of 2.8：1. The median age at diag- nosis was 71 years （range 28-95/inter-quartile range 59-81）, for women median age was 71 （range 28-95） years and was 73 （range 48-92） years for men. The mean annual incidence was 5.4/105 inhabitants. During the time periods 2001-2005 and 2006-2010, the mean annual incidence rates were 5.4/105 for both periods [95% confidence interval （CI）： 4.3-6.5 in 2001-2005 and 4.4-6.4 in 2006-2010, respectively, and 4.7-6.2 for the whole period]. Although the incidence varied over the years （minimum 3.7 to maximum 6.7/105） no increase or decrease in the incidence could be identi- fied. The odds ratio （OR） for CC in women compared to men was estimated to be 2.8 （95% CI： 2.0-3.7）. The OR for women 65 years of age or above compared to below 65 years of age was 6.9 （95% CI：5.0-9.7）, and for women 65 years of age or above compared to the whole group the OR was 4.7 （95% CI： 3.6-6.0）. The OR for age in general, i.e., above or 65 years of age compared to those younger than 65 was 8.3 （95% CI： 6.2-11.1）. During the last decade incidence figures for CC have also been reported from Calgary, Canada dur- ing 2002-2004 （4.6/105） and from Terrassa, Spain dur- ing 2004-2008 （2.6/105）. Our incidence figures from southern Sweden during 2001-2010 （5.4/10s） as well as the incidence figures presented in the studies during the 1990s （Terrassa, Spain during 1993-1997 （2.3/10s）, OI- msted, United States during 1985-2001 （3.1/10s）, Orebro, Sweden during 1993-1998 （4.9/10s）, and Iceland during 1995-1999 （5.2/10s） are all in line with a north- south gradient, something that has been suggested be- fore both for CC and inflammatory bowel disease.CONCLUSION： The observed incidence of CC is com- parable with previous reports from northern Europe and America. The incidence is stable but the female： male ratio seems to be decreasing.

Prevention of Gut Mucosa Inflammation by Two Co-cultures of Lactobacillus plantarum-Bifidobacterium Iongum and Streptococcus thermophilus-Bifidobacterium Iongum

The effect of two fermented milks （FMI, FM2） with lactic acid bacteria and Bifidobacteria on the intestine mucosa was studied. BALB/c mice were divided in groups of non-sensitized or sensitized by oral route to cow＇s milk or colonized by FM1 [10^7 cfu/mL ofBifidobacterium longum （Bfl） and 10^8 cfu/mL of Streptococcus thermophillus （Stl）] and sensitized by oral route to cow＇s milk or colonized by FM2 [10^7 cfu/mL of Bfl and 10^7 cfu/mL ofLactobacillusplantarum （LbO）] and sensitized to cow＇s milk. Blood was sampled and the amount of anti-β-Lactoglobulin （β-Lg） IgG was measured. Mice were sacrificed, fragments of their intestines were isolated to inspect the structural changes of intestinal mucosa. A significant anti-β-Lg response was elicited by oral sensitization in positive control compared to other groups. Inspection of villi structural changes reveal signs of inflammation in challenged group compared with FM1 and FM2 groups, which conserved long villi characteristic of negative controls. The colonization of intestines by BfI-StI and BfI-LbO, and the evaluation of the residual antigenicity of β-Lg in mice sensitized to bovine milk by oral route followed by histological studies, revealed that FM1 and FM2 play protective role and reduce the histological lesions typical of bovine milk allergy.

Protective Effect of Emodin against Lipopolysaccharides-induced Corneal Injury in Rats

Objective To investigate the effect of emodin on lipopolysaccharides （LPS）-induced corneal injury in rats. Methods Three parallel incisions on the central surface of corneal epithelium were made and LPS was applied on them to induce corneal injury in Wistar rats. All rats were randomly divided into emodin group （n=40） and keratitis group （n=40）. Rats in the emodin group received subconjunctival injection of emodin and rats in the keratitis group received its vehicle 30 minutes before LPS exposure. At different time points-1 3, 6, 12, and 24 hours after LPS exposure, the symptoms of all rats were observed and the severity of their ocular inflammation was examined with a slit lamp microscope, then 8 rats in each group were killed through cervical dislocation and their eyes were enucleated and prepared to observe pathological changes of corneal tissue under a light microscope. The activation of nuclear factor-loB （NF-κB） under different condi- tions was determined by Western blot. Immunocytochemistry staining with an antibody against intercellular adhesion molecule-1 （ICAM-1） was performed to identify positive cells in corneal tissues. Results The model of acute keratitis was successfully established in Wistar rats. LPS could induce a typical corneal inflammatory response, such as hyperemia, corneal edema and opacity, which were observed in model rats. Compared with keratitis group, both ocular behaviors and damages of the corneal structure were improved in emodin group. Furthermore, the activation of NF-κB and the expression of ICAM-1 induced by LPS were markedly inhibited in emodin group. Conclusion Emodin can inhibit the activation of NF-κB and the expression of ICAM-I induced by LPS in corneas, protect against acute corneal injury, and improve symptoms in rats.

Inflammatory bowel disease in adolescents:What problems does it pose?

Adolescents with inflammatory bowel disease face daily and long-term challenges that may be difficult for teenagers to manage. The developmental and psychosocial changes unique to this age group include becoming more autonomous and being more vulnerable to peer influence. These changes may lead to problems in medical management such as poor medication adherence and risky behavior. Being aware of these issues will help the medical team provide anticipatory guidance to address these concerns.

Non-specific Arm Pain

Non-specific arm pain is a special clinical condition that can occur in work-related activities that involve maintaining a static position for prolonged periods or repetitive and frequent movements of the hand or entire arm. Such activities include typing on a keyboard, maneuvering a computer mouse, playing musical instruments （such as piano and guitar） and many forms of manual labor. The pain is dull and diffuse; It is localized in the forearm or in the hand but quickly can expand to the entire extremity. Non-specific arm pain is the most frequent type of work-related pain after lower-back pain. It thus has important socio-economic significance as a major cause of absence from work. The designation of ＂non-specific＂ originates from the fact that it has no obvious signs of tissue damage, unlike the ＂specific＂ pain accompanying carpal tunnel syndrome, tenosinovitis de Quervain, or lateral epicondylitis. Suggested causes of the pain include microtrauma of soft tissue followed by an inflammatory reaction, ischemia, fatigue, hyper-sensitization of nociceptors, focal dystonia of the hand and/or psychological stress. Treatment consists of application of NSAIDs, physical modalities, stretching and aerobic exercises. Prevention focuses on ergonomic modification during manual labor or work on a computer.