Inflammatory bowel disease and thromboembolism

Patients with inflammatory bowel disease (IBD) have an increased risk of vascular complications. Thromboembolic complications, both venous and arterial, are serious extraintestinal manifestations complicating the course of IBD and can lead to significant morbidity and mortality. Patients with IBD are more prone to thromboembolic complications and IBD per se is a risk factor for thromboembolic disease. Data suggest that thrombosis is a specific feature of IBD that can be involved in both the occurrence of thromboembolic events and the pathogenesis of the disease. The exact etiology for this special association between IBD and thromboembolism is as yet unknown, but it is thought that multiple acquired and inherited factors are interacting and producing the increased tendency for thrombosis in the local intestinal microvasculature, as well as in the systemic circulation. Clinicians’ awareness of the risks, and their ability to promptly diagnose and manage tromboembolic complications are of vital importance. In this review we discuss how thromboembolic disease is related to IBD, specifically focusing on: (1) the epidemiology and clinical features of thromboembolic complications in IBD; (2) the pathophysiology of thrombosis in IBD; and (3) strategies for the prevention and management of thromboembolic complications in IBD patients.

Intestinal microbiota, probiotics and prebiotics in inflammatory bowel disease

It has been presumed that aberrant immune response to intestinal microorganisms in genetically predisposed individuals may play a major role in the pathogenesis of the inflammatory bowel disease, and there is a good deal of evidence supporting this hypothesis. Commensal enteric bacteria probably play a central role in pathogenesis, providing continuous antigenic stimulation that causes chronic intestinal injury. A strong biologic rationale supports the use of probiotics and prebiotics for inflammatory bowel disease therapy. Many probiotic strains exhibit anti-inflammatory properties through their effects on different immune cells, pro-inflammatory cytokine secretion depression, and the induction of anti-inflammatory cytokines. There is very strong evidence supporting the use of multispecies probiotic VSL#3 for the prevention or recurrence of postoperative pouchitis in patients. For treatment of active ulcerative colitis, as well as for maintenance therapy, the clinical evidence of efficacy is strongest for VSL#3 and Escherichia coli Nissle 1917. Moreover, some prebiotics, such as germinated barley foodstuff, Psyllium or oligofructose-enriched inulin, might provide some benefit in patients with active ulcerative colitis or ulcerative colitis in remission. The results of clinical trials in the treatment of active Crohn’s disease or the maintenance of its remission with probiotics and prebiotics are disappointing and do not support their use in this disease. The only exception is weak evidence of advantageous use of Saccharomyces boulardii concomitantly with medical therapy in maintenance treatment.

Histopathology of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

Nonalcoholic fatty liver disease(NAFLD), a hepatic manifestation of metabolic syndrome, is the most common chronic liver disease, and the prevalence is rapidly increasing worldwide. Nonalcoholic steatohepatitis(NASH), the severe form of NAFLD, can progress to liver cirrhosis and hepatocellular carcinoma(HCC). Although noninvasive clinical scores and image-based diagnosis for NAFLD have improved, histopathological evaluation of biopsy specimens remains the gold standard for diagnosing NAFLD/NASH. Steatosis, lobular inflammation, and hepatocellular ballooning are all necessary components for the diagnosis of NASH; fibrosis is also typically observed. Other histopathological abnormalities commonly observed in NASH include hepatocellular glycogenated nuclei, lipogranulomas, and acidophil bodies. The characteristics of pediatric NAFLD/NASH differ from adult NAFLD/NASH. Specifically, steatosis and portal inflammation are more severe in pediatric NAFLD, while intralobular inflammation and perisinusoidal fibrosis are milder. Although interobserver agreement for evaluating the extent of steatosis and fibrosis is high, agreement is low for intralobular and portal inflammation. A recently reported histological variant of HCC, steatohepatitic HCC(SH-HCC), showsfeatures that resemble non-neoplastic steatohepatitis,and is thought to be strongly associated with underlying NASH.In this report,we review the histopathological features of NAFLD/NASH.

Role of the gut microbiota in inflammatory bowel disease pathogenesis: What have we learnt in the past 10 years?

Our understanding of the microbial involvement in inflammatory bowel disease (IBD) pathogenesis has increased exponentially over the past decade. The development of newer molecular tools for the global assessment of the gut microbiome and the identification of nucleotide-binding oligomerization domain-containing protein 2 in 2001 and other susceptibility genes for Crohn’s disease in particular has led to better understanding of the aetiopathogenesis of IBD. The microbial studies have elaborated the normal composition of the gut microbiome and its perturbations in the setting of IBD. This altered microbiome or “dysbiosis” is a key player in the protracted course of inflammation in IBD. Numerous genome-wide association studies have identified further genes involved in gastrointestinal innate immunity (including polymorphisms in genes involved in autophagy: ATG16L1 and IGRM), which have helped elucidate the relationship of the local innate immunity with the adjacent luminal bacteria. These developments have also spurred the search for specific pathogens which may have a role in the metamorphosis of the gut microbiome from a symbiotic entity to a putative pathogenic one. Here we review advances in our understanding of microbial involvement in IBD pathogenesis over the past 10 years and offer insight into how this will shape our therapeutic management of the disease in the coming years.

Epidemiological studies of migration and environmental risk factors in the inflammatory bowel diseases

Inflammatory bowel diseases(IBD)are idiopathic chronic diseases of the gastrointestinal tract well known to be associated with both genetic and environmental risk factors.Permissive genotypes may manifest into clinical phenotypes under certain environmental influences and these may be best studied from migratory studies.Exploring differences between first and second generation migrants may further highlight the contribution of environmental factors towards the development of IBD.There are few opportunities that have been offered so far.We aim to review the available migration studies on IBD,evaluate the known environmental factors associated with IBD,and explore modern migration patterns to identify new opportunities and candidate migrant groups in IBD migration research.

Prevention of post-operative recurrence of Crohn's disease

Endoscopic and clinical recurrence of Crohn’s disease (CD) is a common occurrence after surgical resection. Smokers, those with perforating disease, and those with myenteric plexitis are all at higher risk of recurrence. A number of medical therapies have been shown to reduce this risk in clinical trials. Metronidazole, thiopurines and anti-tumour necrosis factors (TNFs) are all effective in reducing the risk of endoscopic or clinical recurrence of CD. Since these are preventative agents, the benefits of prophylaxis need to be weighed-against the risk of adverse events from, and costs of, therapy. Patients who are high risk for post-operative recurrence should be considered for early medical prophylaxis with an anti-TNF. Patients who have few to no risk factors are likely best served by a three-month course of antibiotics followed by tailored therapy based on endoscopy at one year. Clinical recurrence rates are variable, and methods to stratify patients into high and low risk populations combined with prophylaxis tailored to endoscopic recurrence would be an effective strategy in treating these patients.

Oral manifestation in inflammatory bowel disease:A review

Inflammatory bowel diseases (IBDs), including Crohn’s disease (CD) and ulcerative colitis, not only affect the intestinal tract but also have an extraintestinal involvement within the oral cavity. These oral manifestations may assist in the diagnosis and the monitoring of disease activity, whilst ignoring them may lead to an inaccurate diagnosis and useless and expensive workups. Indurated tag-like lesions, cobblestoning, and mucogingivitis are the most common specific oral findings encountered in CD cases. Aphthous stomatitis and pyostomatitis vegetans are among non-specific oral manifestations of IBD. In differential diagnosis, side effects of drugs, infections, nutritional deficiencies, and other inflammatory conditions should also be considered. Treatment usually involves managing the underlying intestinal disease. In severe cases with local symptoms, topical and/or systemic steroids and immunosuppressive drugs might be used.

Periodontal disease is associated with increased coronary heart disease risk:A meta-analysis based on 38 case-control studies

AIM: To investigate whether periodontal disease(PD) is associated with increasing coronary heart disease(CHD) risk by performing a meta-analysis.METHODS: Two authors independently searched Pub Med and China National Knowledge Infrastructure up to January 10 th, 2013 for relevant case-control studies that investigated the association between PD and CHD. After quality assessment using Newcastle-Ottawa Scale and data extraction by two independent authors, the overall and subgroup meta-analyses were performed and publication bias were examined using the Comprehensive Meta-Analysis V2 software. Potential publication bias was assessed using visual inspection of the funnel plots, Egger linear regression test, and trims and fill method.RESULTS: Finally 38 relevant case-control studies were identified, involving 4950 CHD patients and 5490 controls. Eleven studies were rated low quality and 27 were high quality. Based on random-effects, a significant association was identified between PD and CHD(OR 3.79, 95%CI: 2.23-6.43, P < 0.001, I2 = 98.59%), and sensitivity analysis showed that this result was robust. Subgroup analyses according to adjusted/unadjusted ORs, source of control, methodological quality, end point, assessment of PD/CHD, and ethnicity also indicated a significant association. Publication bias was detected, and the estimated OR including the "missing" studies did not substantially differ from our estimate with adjustment for missing studies(OR 4.15, 95%CI: 2.62-6.54, P < 0.001).CONCLUSION: Based on the meta-analysis, PD is probably associated with CHD risk independently and significantly.

Temporal trends in inflammatory bowel disease publications over a 19-years period

AIM: To determine whether temporal changes occurred in the pediatric vs adult inflammatory bowel disease(IBD), both in terms of number and type of yearly published articles.METHODS:We aimed to evaluate all Pub Med-registered articles related to the field of IBD from January1,1993 and until December 31,2011.We searched for articles using the key words"inflammatory bowel disease"or"Crohn’s disease"or"ulcerative colitis"or"undetermined colitis",using the age filters of"child"or"adult".We repeated the search according to the total number per year of articles per type of article,for each year of the specified period.We studied randomized controlled trials,clinical trials,case reports,meta-analyses,letters to the editor,reviews,systematic reviews,practice guidelines,and editorials.RESULTS:We identified 44645 articles over the 19year-period.There were 8687 pediatric-tagged articles vs 19750 adult-tagged articles.Thus 16208 articles were unaccounted and not assigned a"pediatric"or"adult"tag by Pub Med.There was an approximately3-fold significant increase in all articles recorded both in pediatric and adult articles.This significant increase was true for nearly every category of article but the number of clinical trials,meta-analysis,and randomized controlled trials increased proportionally more than the number of"lower quality"articles such as editorials or letters to the editor.Very few guidelines were published every year.CONCLUSION:There is a yearly linear increase in publications related to IBD.Relatively,there are more and more clinical trials and higher quality articles.

TGF-β1 Precursor and CD8 Are Potential Prognostic and Predictive Markers in Operated Breast Cancer

The transforming growth factor β1（TGF-β1） and CD8-positive T cells are two important immune factors that function at opposite directions. The purpose of this study was to verify the relationship between the two factors and their associations with long-term effects of adjuvant chemotherapy or endocrine therapy in breast cancer. Expression of TGF-β1 precursor and CD8 was immunohistochemically detected on surgically-obtained tumor samples of 130（stageⅠ–Ⅲ） invasive breast carcinomas from Chinese subjects, who were followed up for a mean time of 112 months. Interstitial CD8-positive cells and TGF-β1 precursor-positive cells adjacent to tumor nests were counted. Infiltration of CD8-positive lymphocytes into tumor nests and TGF-β1 precursor expression in tumor cells were observed and survival analysis was performed. Our results showed that density of interstitial CD8-positive lymphocytes was an independent adverse prognostic factor for distant disease-free survival（DDFS）（HR=8.416, 95% CI=1.636–43.292, P=0.011） in hormone receptor-positive patients who were on adjuvant endocrine therapy. For breast cancer patients who did not receive adjuvant chemotherapy, those without infiltration of CD8-positive cells into tumor nests had a shorter overall survival（OS） than their counterparts with CD8-positive cell infiltration into tumor nests（Log-Rank, P=0.003）. But OS of patients without infiltration of CD8-positive cells into tumor nests was significantly prolonged by adjuvant chemotherapy（Log-Rank, P=0.013） and paralleled that of patients with CD8-positive cell infiltration. Although OS was shorter in the tumor cell TGF-β1 precursor（t-TGF-β1-pre）-positive patients than in the negative patients in patients without recieiving chemotherapy（P=0.053）, OS of t-TGF-β1-pre-positive patients was significantly prolonged by adjuvant chemotherapy（P=0.035） and was longer than that of t-TGF-β1-pre-negative patients. Analysis showed that t-TGF-β1-pre was an independent positive prognostic factor for DDFS（HR=0.392 95% CI=0.157–0.978, P=0.045） in patients who received adjuvant chemotherapy. This study suggested that density of interstitial CD8-positive lymphocytes was of prognostic value in hormone receptor-positive patients who received adjuvant endocrine therapy. Our study verified that adverse immunologic signatures consisting of absence of CD8-positive cells in tumor nests or expression of TGF-β1 precursor in tumor cells in breast cancer were associated with worse prognosis and significantly improved long-term survival with adjuvant chemotherapy, respectively.

Adjuvant therapy sparing in rectal cancer achieving complete response after chemoradiation

AIM: To evaluate the long-term results of conventional chemoradiotherapy and laparoscopic mesorectal excision in rectal adenocarcinoma patients without adjuvant therapy.

Helicobacter pylori eradication with moxifloxacin-containing therapy following failed first-line therapies in South korea

AIM: To investigate moxifloxacin-containing triple therapy as second-line treatment for Helicobacter pylori (H. pylori) infection following failed first-line treatment.

Large-scale screening of disease model through ENU mutagenesis in mice

Manipulation of mouse genome has merged as one of the most important approaches for studying genefunction and establishing the disease model because of the high homology between human genome and mouse genome. In this study, the chemical mutagen ethylnitrosourea (ENU) was employed for inducing germ cell mutations in maleC57BL/6J mice. The first generation (G1) of the backcrossof these mutated mice, totally 3172, was screened for abnor-mal phenotypes on gross morphology, behavior, learning and memory, auditory brainstem response (ABR), electrocardio-gram (ECG), electroretinogram (ERG), flash-visual evoked potential (F-VEP), bone mineral density, and blood sugarlevel. 595 mice have been identified with specific dominantabnormalities. Fur color changes, eye defects and hearing loss occurred at the highest frequency. Abnormalities related to metabolism alteration are least frequent. Interestingly, eye defects displayed significant left-right asymmetry and sexpreference. Sex preference is also observed in mice with ab-normal bone mineral density. Among 104 G1 generation mutant mice examined for inheritability, 14 of them have been confirmed for passing abnormal phenotypes to their progenies. However, we did not observe behavior abnormali-ties of G1 mice to be inheritable, suggesting multi-gene con-trol for these complicated functions in mice. In conclusion, the generation of these mutants paves the way for under-standing molecular and cellular mechanisms of these ab-normal phenotypes, and accelerates the cloning of disease-related genes.

基于深度卷积神经网络算法和先验知识构建冠心病患者大鱼际望诊模型的思路与方法

基于全息理论的中医望诊可以辅助诊断西医疾病,但目前中医望诊主要依靠名老中医药专家的经验传承,存在望诊客观化、标准化程度不够,缺乏行业内认可度高的望诊转化技术的问题。而望诊融合人工智能信息化技术,可以提升中医望诊客观化、标准化的水平,可以有效地降低疾病的恶化率和病死率,促进中医望诊经验的转化。据此,结合前期开展的大鱼际特征与冠心病关系研究,得出大鱼际望诊可以用于冠心病早期预警筛查。以大鱼际望诊和冠心病之间的关系为例,将先验知识和深度卷积神经网络算法深度融合,将特征提取和分类合为一体,利用深度学习端对端的显著特点,输入观察到的原始大鱼际图像像素数据或信息,通过对大鱼际照片的大量深度学习,构建冠心病患者的关键特征要素,融合先验知识后,输出是否为冠心病的分类结果,中间为深层的网络结构。这一思路将提出一种中医望诊客观化、标准化的智能化算法,促进中医望诊经验的转化思路与方法,以提高基层群众的疾病预警筛查能力,服务“健康中国”战略。

HSD17B6的主要功能及其在内分泌代谢和肿瘤中的作用

羟基类固醇脱氢酶是醛酮还原酶和短链脱氢酶⁃还原酶超家族的成员,对于类固醇激素在体内发挥正常功能起着至关重要的作用。HSD17B6是羟基类固醇脱氢酶中的一种,在体内主要参与雄激素的代谢和生物合成,产生雌激素受体β的高亲和力配体,进而可能影响体内糖脂代谢,造成内分泌及生殖系统的紊乱与疾病的发生。HSD17B6表达异常也与机体免疫功能有关,可参与肿瘤的发生与发展,作为潜在生物标志物用于肿瘤的诊断与评估,为药物或靶向治疗提供参考信息。尽管其对疾病影响的精细机制尚不明确,但HSD17B的功能丧失可能对机体造成不同程度的损伤。本文就HSD17B6在代谢病和肿瘤方面的作用进行综述。

HDP产妇产后发生慢性肾脏病风险因素

目的:分析妊娠期高血压疾病(HDP)发生产后慢性肾脏病(CKD)风险因素。方法:回顾分析2017年7月-2021年6月于本院建档产前检查的孕产妇病例记录共3185例,其中HDP产妇726例纳入观察组,非HDP产妇2459例纳入对照组。收集两组孕前情况、既往史、个人史、家族史、孕产史等临床资料,比较两组及产后发生CKD患者的临床资料,分析HDP产妇发生CKD的风险及相关风险因素。结果:观察组年龄和孕前体质指数高于对照组,初次妊娠、剖宫产及发生分娩并发症的比例高于对照组,CKD发病率(5.0%)高于对照组(1.4%)(均P<0.05)。经分析,观察组发生CKD的风险是对照组的5.54倍(95%CI3.43~10.65);HDP产妇矫正干扰因素后,分娩年龄≥35岁仍是CKD发生的风险因素(OR=2.31,95%CI1.30~3.89),分娩≥2次的HDP产妇发生CKD的风险低于初产妇(OR=0.34,95%CI0.14~0.74)(均P<0.05)。结论:HDP产妇发生CKD的风险较高,特别是年龄≥35岁的高龄产妇,提示临床在分娩后应嘱产妇定期检查肾功能,以便及时干预治疗。

疼痛管理联合加速康复外科理念在肺癌合并冠心病患者围手术期的应用效果

目的探讨疼痛管理联合加速康复外科理念在肺癌合并冠心病患者围手术期的应用效果。方法根据干预方式的不同将62例肺癌合并冠心病手术患者分为观察组(n=33)和对照组(n=29),对照组患者围手术期给予常规干预,观察组患者在对照组的基础上给予疼痛管理联合加速康复外科理念。比较两组患者的围手术期指标、疼痛情况[视觉模拟评分法(VAS)]、负性情绪[汉密尔顿焦虑量表(HAMA)、汉密尔顿抑郁量表(HAMD)]及术后并发症发生情况。结果观察组患者首次排气时间、首次排便时间、引流管拔除时间、住院时间均短于对照组,术后并发症总发生率低于对照组,差异均有统计学意义(P﹤0.05)。术后1天、3天、1周,两组患者VAS评分均呈下降趋势,且观察组患者VAS评分均低于对照组,差异均有统计学意义(P﹤0.05)。干预后,两组患者HAMA、HAMD评分均低于本组干预前,观察组患者HAMA、HAMD评分均低于对照组,差异均有统计学意义(P﹤0.05)。结论疼痛管理联合加速康复外科理念应用于肺癌合并冠心病患者围手术期,能够减轻术后疼痛、改善负性情绪、降低术后并发症发生率,并且促进患者术后恢复。

森田疗法门诊操作规则的专家意见

森田疗法已诞生100余年,住院森田疗法可操作性强、易掌握,通过4期治疗就可改善许多难治神经症,但更多神经症是在门诊治疗,无法使用住院森田疗法,因此门诊操作专家意见的制定尤为重要。本文结合国内外文献,经国内森田疗法专家多次讨论,起草了第1版门诊森田疗法操作的专家意见,制定门诊三阶段的森田疗法操作规则:病因分析阶段,通过森田疗法理论指导,分析发病因素,提高对治疗依从性,降低抵抗;作业阶段,指导患者投入建设性意义行动,实现顺其自然为所当为原则,达到治疗目的;陶冶性格、充实生活阶段,注重正面信息关注,扩大行动范围、内容,提高适应复杂生活的能力,预防因能力不足导致的复发。该规则为国内门诊森田疗法的推广,使更多神经症等心理疾病患者在门诊就可得到森田疗法治疗奠定基础。

老年眼病中西医结合专科护理人才培养的构思及展望

随着医学模式和现代护理发展的转变,护理专科化已经成为国内、外学者关注的热点问题。老年眼病中西医结合专科护理人才作为促进眼健康事业发展的重要组成部分,为我国眼健康事业的发展提供了重要资源。本文通过梳理国内外文献,发现我国老年眼病中西医结合领域临床经验丰富的高学历和高职称的护理人员严重缺乏,护理人才尚未形成系统性的培养体系,针对性和系统性的护理知识更为匮乏。本研究针对现有成果和存在的问题进行总结,根据老年眼病中西医结合护理人才培养需求,提出了初步的构思与展望,如建立院校基地联合的培养模式,以学科为基础,以技能为先导,加强老年眼病中西医结合护理队伍的培训,完善老年眼病中西医结合护理队伍的培养体系,建设高素质老年眼病中西医结合护理队伍,推动眼科专科护理高质量发展,对于推动我国老年眼病的防治,提升老年患者眼健康整体水平具有一定意义。

基于“气血-络脉-玄府轴”新视角探讨视网膜血管性疾病的治疗

“气血学说”“络病学说”“玄府学说”是中医基础理论和中医眼科的重要组成部分,三者同轴一体,在生理和病机上密不可分。从中医学整体观念出发,脏腑为本,目为标,气血-络脉-玄府轴是脏腑与目联系的枢纽;在局部辨证的基础上,“气血-络脉-玄府轴”的稳态失衡是视网膜血管性疾病(RVD)在眼底证候的微观体现。在病症结合视角下探究RVD的临床特点,其具有气血不和、络脉失调、玄府郁闭的证候特征,核心病机可概括为“气血-络脉-玄府轴失调”;由此提出和气血、通络脉、开玄府为RVD的基本治疗原则,须贯穿疾病治疗的始终,为RVD的中医治疗提供新的思路。