Overview and progress of X-nuclei magnetic resonance imaging in biomedical studies

Proton nuclear(^(1)H)is the observed nucleus on which most magnetic resonance imaging(MRI)applications depend.Most traditional^(1)H MRI can provide structural and functional information about organisms,while various non-proton nuclei(X-nuclei)MRI can provide more metabolic information.However,due to the relatively poor signal-to-noise ratio(SNR)of X-nuclei MRI,their applications are quite rare compared to^(1)H.Benefit from the rapid developments of MRI hardware and software technologies,X-nuclei MRI has recently attracted increasing interests in biomedical research.This review firstly introduces some current methods to improve the SNR of X-nuclei MRI.Secondly,this review describes biomedical applications of X-nuclei MRI,especially focusing on the current use of X-nuclei(^(13)C,^(17)O,^(19)F,^(23)Na and^(31)P)MRI to study related diseases in different organs,including the brain,liver,kidney,heart and bone.Finally,perspectives studies on X-nuclei imaging and its potential applications are described in biomedical research.

Outcomes of gout in patients with cirrhosis:A national inpatient sample-based study

BACKGROUND Hyperuricemia is a prerequisite for the development of gout.Elevated serum uric acid(UA)levels result from either overproduction or decreased excretion.A positive correlation between serum UA levels,cirrhosis-related complications and the incidence of nonalcoholic fatty liver disease has been established,but it is unknown whether hyperuricemia results in worsening cirrhosis outcomes.We hypothesize that patients with cirrhosis will have poorer gout outcomes.AIM To explore the link between cirrhosis and the incidence of gout-related complications.METHODS This was a cross-sectional study.The national inpatient sample was used to identify patients hospitalized with gout,stratified based on a history of cirrhosis,from 2001 to 2013 via the International Classification of Diseases,Ninth Revision,Clinical Modification codes.Primary outcomes were mortality,gout complications and joint interventions.Theχ^(2)test and independent t-test were performed to assess categorical and continuous data,respectively.Multiple logistic regression was used to control for confounding variables.RESULTS Patients without cirrhosis were older(70.37±13.53 years vs 66.21±12.325 years;P<0.05).Most patients were male(74.63%in the cirrhosis group vs 66.83%;adjusted P<0.05).Patients with cirrhosis had greater rates of mortality(5.49%vs 2.03%;adjusted P<0.05),gout flare(2.89%vs 2.77%;adjusted P<0.05)and tophi(0.97%vs 0.75%;adjusted P=0.677).Patients without cirrhosis had higher rates of arthrocentesis(2.45%vs 2.21%;adjusted P<0.05)and joint injections(0.72%vs 0.52%;adjusted P<0.05).CONCLUSION Gout complications were more common in cirrhosis.Those without cirrhosis had higher rates of interventions,possibly due to hesitancy with performing these interventions given the higher complication risk in cirrhosis.

Diagnostic value of matrix metalloproteinases 2, 7 and 9 in urine for early detection of colorectal cancer

BACKGROUND A noninvasive biomarker with high diagnostic performance is urgently needed for the early diagnosis of colorectal cancer(CRC).AIM To evaluate the diagnostic value of matrix metalloproteinases(MMPs)2,7 and 9 in urine for CRC.METHODS Of 59 healthy controls,47 patients with colon polyps and 82 patients with CRC were included in this study.Carcinoembryonic antigen(CEA)in serum and MMP2,MMP7,and MMP9 in urine were detected.The combined diagnostic model of the indicators was established by binary logistic regression.The receiver operating characteristic curve(ROC)of the subjects was used to evaluate the independent and combined diagnostic value of the indicators.RESULTS The MMP2,MMP7,MMP9,and CEA levels in the CRC group differed significantly from levels in the healthy controls(P<0.05).The levels of MMP7,MMP9,and CEA also differed significantly between the CRC group and the colon polyps group(P<0.05).The area under the curve(AUC)distinguishing between the healthy control and the CRC patients using the joint model with CEA,MMP2,MMP7 and MMP9 was 0.977,and the sensitivity and specificity were 95.10%and 91.50%,respectively.For early-stage CRC,the AUC was 0.975,and the sensitivity and specificity were 94.30%and 98.30%,respectively.For advanced stage CRC,the AUC was 0.979,and the sensitivity and specificity were 95.70%and 91.50%,respectively.Using CEA,MMP7 and MMP9 to jointly established a model distinguishing the colorectal polyp group from the CRC group,the AUC was 0.849,and the sensitivity and specificity were 84.10%and 70.20%,respectively.For early-stage CRC,the AUC was 0.818,and the sensitivity and specificity were 76.30%and 72.30%,respectively.For advanced stage CRC,the AUC was 0.875,and the sensitivity and specificity were 81.80%and 72.30%,respectively.CONCLUSION MMP2,MMP7 and MMP 9 may exhibit diagnostic value for the early detection of CRC and may serve as auxiliary diagnostic markers for CRC.

住院患者认知障碍识别和信息管理的整合性综述

目的旨在对目前提供急性照护的医院识别认知障碍患者以及在病历中记录和管理认知相关信息的实际情况及政策要求和推荐方法进行综述。方 法采用Whittemore和Knaf1的五步法,系统检索Medline,CINAHL和Scopus数据库,并检索了灰色文献来源。纳人了提供急性照护的医院已实施的患者认知障碍识别和认知信息管理相关的文献。采用混合方法评价工具和灰色文献质量评估清单对文章质量进行评价。采用主题分析法呈现和整合结果。该综述已在PROSPERO预注册(CRD42022343577)。结果 共22篇原始研究文献和10篇政府/行业文件被纳人分析。结果显示,实践和政策之间存在差距。尽管在政策层面上高度重视认知障碍的识别、认知相关信息的透明度,以及与患者、家属和照顾者(如适用)之间的互动,但有时在临床实践中,认知评估是非正式的,患者的认知相关信息未作记录,与患者、家属和照顾者的互动也存在不足。结 论.通过整合认知评估,利用信息技术开发信息管理综合系统,建立相关法律法规,提供教育与和培训,并采用国家层面的策略,有可能显著改善对认知障碍患者的识别和护理。

Non-invasive means of measuring hepatic fat content

Hepatic steatosis affects 20% to 30% of the general adult population in the western world. Currently, the technique of choice for determining hepatic fat deposition and the stage of fibrosis is liver biopsy. However, it is an invasive procedure and its use is limited, particularly in children. It may also be subject to sampling error. Non-invasive techniques such as ultrasound, computerised tomography (CT), magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (1H MRS) can detect hepatic steatosis, but currently cannot distinguish between simple steatosis and steatohepatitis, or stage the degree of fibrosis accurately. Ultrasound is widely used to detect hepatic steatosis, but its sensitivity is reduced in the morbidly obese and also in those with small amounts of fatty infiltration. It has been used to grade hepatic fat content, but this is subjective. CT can detect hepatic steatosis, but exposes subjects to ionising radiation, thus limiting its use in longitudinal studies and in children. Recently, magnetic resonance (MR) techniques using chemical shift imaging have provided a quantitative assessment of the degree of hepatic fatty infiltration, which correlates well with liver biopsy results in the same patients. Similarly, in vivo 1H MRS is a fast, safe, non-invasive method forthe quantification of intrahepatocellular lipid (IHCL) levels. Both techniques will be useful tools in future longitudinal clinical studies, either in examining the natural history of conditions causing hepatic steatosis (e.g. non-alcoholic fatty liver disease), or in testing new treatments for these conditions.

Diagnosis of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the commonest cancers worldwide, particularly in parts of the developing world, and is increasing in incidence. This article reviews the current modalities employed for the diagnosis of HCC, including serum markers, radiological techniques and histological evaluation, and summarises international guidelines for the diagnostic approach to HCC.

Transient elastography for the assessment of chronic liver disease: Ready for the clinic?

Transient elastography is a recently developed non- invasive technique for the assessment of hepatic fi brosis. The technique has been subject to rigorous evaluation in a number of studies in patients with chronic liver disease of varying aetiology. Transient elastography has been compared with histological assessment of percutaneous liver biopsy, with high sensitivity and specificity for the diagnosis of cirrhosis, and has also been used to assess pre-cirrhotic disease. However, the cut-off values between different histological stages vary substantially in different studies, patient groups and aetiology of liver disease. More recent studies have examined the possible place of transient elastography in clinical practice, including risk stratifi cation for the development of complications of cirrhosis. This review describes the technique of transient elastography and discusses the interpretation of recent studies, emphasizing its applicability in the clinical setting.

Oily fish, coffee and walnuts: Dietary treatment for nonalcoholic fatty liver disease

Rates of non-alcoholic fatty liver disease(NAFLD) are increasing worldwide in tandem with the metabolic syndrome, with the progressive form of disease, nonalcoholic steatohepatitis(NASH) likely to become the most common cause of end stage liver disease in the not too distant future. Lifestyle modification and weight loss remain the main focus of management in NAFLD and NASH, however, there has been growing interest in the benefit of specific foods and dietary components on disease progression, with some foods showing protective properties. This article provides an overview of the foods that show the most promise and their potential benefits in NAFLD/NASH, specifically; oily fish/fish oil, coffee, nuts, tea, red wine, avocado and olive oil. Furthermore, it summarises results from animal and human trials and highlights potential areas for future research.

Risk factors for colonoscopic perforation: A population-based study of 80118 cases

AIM: To assess the incidence and risk factors associated with colonic perforation due to colonoscopy. METHODS: This was a retrospective cross-sectional study. Patients were retrospectively eligible for inclusion if they were 18 years and older and had an inpatient or outpatient colonoscopy procedure code in any facility within the Geisinger Health System during the period from January 1, 2002 to August 25, 2010. Data are presented as median and inter-quartile range, for continuous variables, and as frequency and percentage for categorical variables. Baseline comparisons across those with and without a perforation were made using the two-sample t -test and Pearson's χ2 test, as appropriate.RESULTS: A total of 50 perforations were diagnosed out of 80118 colonoscopies, which corresponded to an incidence of 0.06% (95%CI: 0.05-0.08) or a rate of 6.2 per 10000 colonoscopies. All possible risk factors associated with colonic perforation with a P -value < 0.1 were checked for inclusion in a multivariable logbinomial regression model predicting 7-d colonic perforation. The final model resulted in the following risk factors which were significantly associated with risk of colonic perforation: age, gender, body mass index, albumin level, intensive care unit (ICU) patients, inpatient setting, and abdominal pain and Crohn's disease as indications for colonoscopy. CONCLUSION: The cumulative 7 d incidence of colonic perforation in this cohort was 0.06%. Advanced age and female gender were significantly more likely to have perforation. Increasing albumin and BMI resulted in decreased risk of colonic perforation. Having a colonoscopy indication of abdominal pain or Crohn's disease resulted in a higher risk of colonic perforation. Colonoscopies performed in inpatients and particularly the ICU setting had substantially greater odds of perforation. Biopsy and polypectomy did not increase the risk of perforation and only three perforations occurred with screening colonoscopy.

Imaging of liver cancer

Improvements in imaging technology allow exploitation of the dual blood supply of the liver to aid in the identif ication and characterisation of both malignant and benign liver lesions. Imaging techniques available include contrast enhanced ultrasound, computed tomography and magnetic resonance imaging. This review discusses the application of several imaging techniques in the diagnosis and staging of both hepatocellular carcinoma and cholangiocarcinoma and outlines certain characteristics of benign liver lesions. The advantages of each imaging technique are highlighted, while underscoring the potential pitfalls and limitations of each imaging modality.

Current and future applications of magnetic resonance imaging and spectroscopy of the brain in hepatic encepha-lopathy

Hepatic encephalopathy （HE） is a common neuropsychiatric abnormality, which complicates the course of patients with liver disease and results from hepatocellular failure and/or portosystemic shunting. The manifestations of HE are widely variable and involve a spectrum from mild subclinical disturbance to deep coma. Research interest has focused on the role of circulating gut-derived toxins, particularly ammonia, the development of brain swelling and changes in cerebral neurotransmitter systems that lead to global CNS depression and disordered function. Until recently the direct investigation of cerebral function has been difficult in man. However, new magnetic resonance imaging （MRI） techniques provide a non-invasive means of assessment of changes in brain volume （coregistered MRI） and impaired brain function （fMRI）, while proton magnetic resonance spectroscopy （^1H MRS） detects changes in brain biochemistry, including direct measurement of cerebral osmolytes, such as myoinositol, glutamate and glutamine which govern processes intrinsic to cellular homeostasis, including the accumulation of intracellular water. The concentrations of these intracellular osmolytes alter with hyperammonaemia. MRS-detected metabolite abnormalities correlate with the severity of neuropsychiatric impairment and since MR spectra return towards normal after treatment, the technique may be of use in objective patient monitoring and in assessing the effectiveness of various treatment regimens.

Quantitative risk of positive family history in developing colorectal cancer: A meta-analysis

BACKGROUND Positive family history is a risk factor for development of colorectal cancer.Despite numerous studies on the topic,the absolute risk in patients with a positive family history remains unclear and therefore studies are lacking to validate non-invasive screening methods in individuals with positive family history.AIM To quantify the risk of colorectal cancer in individuals with a positive family history.METHODS A comprehensive electronic literature search was performed using PubMed from January 1955 until November 2017,EMBASE from 1947 until 2018,and Cochrane Library without date restrictions.Two independent reviewers conducted study selection,data extraction and quality assessment.A meta-analysis of Mantel-Haenzel relative risks was performed using the random effects model.Newcastle-Ottawa scale was used to score the quality of selected papers.Funnel plot and Egger’s regression test was performed to detect publication bias.Subgroup analysis was performed comparing Asian and non-Asian studies.Sensitivity analyses were performed to rule out the effect of the timing of the study,overall quality,the main outcome and the effect of each individual study in overall result.RESULTS Forty-six out of 3390 studies,including 906981 patients were included in the final analysis.41 of the included studies were case-control and 5 were cohort.A positive family history of colorectal cancer in first-degree relatives was associated with significantly increased risk of colorectal cancer with a relative risk of 1.87(95%CI:1.68-2.09;P<0.00001).Cochrane Q test was significant(P<0.00001,I2=90%).Egger’s regression test showed asymmetry in the funnel plot and therefore the Trim and Fill method was used which confirmed the validity of the results.There was no difference between Asian versus non-Asian studies.Results remained robust in sensitivity analyses.CONCLUSION Individuals with a positive family history of colorectal cancer are 1.87 times more likely to develop colorectal cancer.Screening guidelines should pay specific attention to individuals with positive family history and further studies need to be done on validating current screening methods or developing new modalities in this high-risk population.

Rise of sodium-glucose cotransporter 2 inhibitors in the management of nonalcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in the Western world. It is more prevalent in male gender, and with increasing age, obesity, and insulin resistance. Besides weight loss, there are limited treatment options. The use of anti-diabetic medications has been studied with mixed results. In this review, we discuss the use of anti-diabetic medications in the management of NAFLD with a specific focus on sodium-glucose cotransporter 2 inhibitors. We shed light on the evidence supporting their use in detail and discuss limitations and future directions.

Expression of AID, P53, and Mlh1 proteins in endoscopically resected differentiated-type early gastric cancer

AIM: To analyze the expression of the tumor-related proteins in differentiated-type early gastric carcinoma (DEGC) samples. METHODS: Tumor specimens were obtained from 102 patients (75 males and 27 females) who had received an endoscopic tumor resection at Tottori University Hospital between 2007 and 2009. Ninety-one cancer samples corresponded to noninvasive or intramucosal carcinoma according to the Vienna classification system, and 11 samples were submucosal invasive carcinomas. All of the EGCs were histologically differentiated carcinomas. All patients were classified as having Helicobacter pylori (H. pylori) infections by endoscopic atrophic changes or by testing seropositive for H. pylori IgG. All of the samples were histopathologically classified as either tubular or papillary adenocarcinoma according to their structure. The immunohistochemical staining was performed in a blinded manner with respect to the clinical information. Two independent observers evaluated protein expression. All data were statistically analyzed then. RESULTS: The rates of aberrant activation-induced cytidine deaminase (AID) expression and P53 overexpression were both 34.3% in DEGCs. The expression of Mlh1 was lost in 18.6% of DEGCs. Aberrant AID expression was not significantly associated with P53 overexpression in DEGCs. However, AID expression was associated with the severity of mononuclear cell activity in the non-cancerous mucosa adjacent to the tumor (P = 0.064). The rate of P53 expression was significantly greater in flat or depressed tumors than in elevated tumors. The frequency of Mlh1 loss was significantly increased in distal tumors, elevated gross-type tumors, papillary histological-type tumors, and tumors with a severe degree of endoscopic atrophic gastritis (P < 0.05). CONCLUSION: Aberrant AID expression, P53 overexpression, and the loss of Mlh1 were all associated with clinicopathological features and gastric mucosal alterations in DEGCs. The aberrant expression of AID protein may partly contribute to the induction of nuclear P53 expression.

Exploitation of host clock gene machinery by hepatitis viruses B and C

Many aspects of cellular physiology display circadian(approximately 24-h)rhythms.Dysfunction of the circadian clock molecular circuitry is associated with human health derangements,including neurodegeneration,increased risk of cancer,cardiovascular diseases and the metabolic syndrome.Viruses triggering hepatitis depend tightly on the host cell synthesis machinery for their own replication,survival and spreading.Recent evidences support a link between the circadian clock circuitry and viruses’biological cycle within host cells.Currently,in vitro models for chronobiological studies of cells infected with viruses need to be implemented.The establishment of such in vitro models would be helpful to better understand the link between the clock gene machinery and viral replication/viral persistence in order to develop specifically targeted therapeutic regimens.Here we review the recent literature dealing with the interplay between hepatitis B and C viruses and clock genes.

The effects of glycyrrhizic acid and glabridin in the regulation of CXCL5 inflammation gene on acceleration of wound healing

Objective: To evaluate the anti-inflammatory property of both glycyrrhizic acid(GA)and glabridin in reducing inflammation to accelerate wound regeneration on 3T3-L1 and NIH-3T3 fibroblast cell lines.Methods: Cell proliferation and viability assay(MTT assay), scratch wound healing assays,and quantitative real-time PCR were conducted to investigate the effects on cell proliferation,cell migration, and expression of CXC chemokine ligand 5 inflammation gene respectively.Results: Results showed that at a low concentration of 1 × 10^(-8)mol/L, glabridin down regulated cell proliferation in NIH-3T3 significantly, suggesting its involvement in ERK1/2 signaling pathway. GA and glabridin significantly accelerated cell migration through wound healing in both 3T3-L1 and NIH-3T3 and significantly down regulated the expression of CXC chemokine ligand 5 in 3T3-L1 at concentration 1 × 10^(-8)mol/L,indicating the possible involvement of nuclear factor-k B and cyclooxygenase 2 transcriptions modulation.Conclusions: Both GA and glabridin can serve as potential treatment for chronic inflammatory disease, and glabridin as an oncogenic inhibitor due to its anti-proliferative property.

Seroprevalence of Helicobacter pylori in dyspeptic patients and its relationship with HIV infection,ABO blood groups and life style in a university hospital,Northwest Ethiopia

AIM： To determine the prevalence of Helicobacter pylori （H pylori） among dyspeptic patients and to assess the relationship between Hpylori infection, blood group, HIV infection and life style of the patients. METHODS： In a hospital-based cross-sectional study, patients attending Outpatient Department of University of Gondar Hospital were enrolled. Socio-demographic information was collected using questionnaires. Serum was analyzed for anti-H pylori IgG antibodies using a commercial kit. HIV serostatus was determined by enzyme-linked immunosorbent assay （ELISA）. Blood grouping was performed by slide agglutination tests. RESULTS： A total of 215 dyspeptic patients were included in the study. One hundred and sixteen patients （54%） were females and 99 （46%） were males. Anti-H pylori IgG antibodies were detected in sera of 184 （85.6%） patients. The prevalence was significantly higher in patients aged 50 years and above. Twenty point five percent of the patients were found to be seropositive for HIV. No significant association was found between sex, ABO blood groups, consumption of spicy diets, socioeconomic status and seropositivity for Hpylori. However,alcohol consumption was significantly associated with H pylori serology. CONCLUSION： The prevalence of H pylori infection is associated with a history of alcohol intake and older age. The effect of different diet, alcohol and socioeconomic status as risk factors for H pylori infection needs further study.

Psychometric Properties of the Swedish Version of the Fear of Complications Questionnaire

Objectives: To translate and evaluate the psychometric properties of the Swedish version of the Fear of Complications Questionnaire. Design: Cross-sectional study design and scale development. Settings: Totally, 469 adults (response rate 63.5%) with Type 1 diabetes completed the questionnaires. Participants were recruited from two university hospitals in Sweden. Participants: Eligible patients were those who met the following inclusion criteria: diagnosed with Type 1 diabetes, diabetes duration of at least 1 year and aged at least 18 years. Methods: The Fear of Complications Questionnaire was translated using the forward-backward translation method. Factor analyses of the questionnaire were performed in two steps using both exploratory and confirmatory factor analysis. Convergent validity was examined using the Hospital Anxiety and Depression Scale and the Fear of Hypoglycaemia Fear Survey. Internal consistency was estimated using Cronbach’s alpha. Results: Exploratory factor analysis supported a two-factor solution. One factor contained three items having to do with fear of kidney-related complications and one factor included the rest of items concerning fear of other diabetes-related complications, as well as fear of complications in general. Internal consistency was high Cronbach’s alpha 0.96. The findings also gave support for convergent validity, with significant positive correlations between measures (r = 0.51 to 0.54). Conclusion: The clinical relevance of the identified two-factor model with a structure of one dominant subdomain may be considered. We suggest, however a one-factor model covering all the items as a relevant basis to assess fear of complications among people with Type 1 diabetes.

Carcinoma ex pleomorphic adenoma of the sublingual gland:a case report

We report a case of carcinoma ex pleomorphic adenoma of a sublingual gland in a 70-year-old man.Under a clinical diagnosis of benign salivary gland tumor,excision of the mass with the sublingual salivary gland in an en bloc fashion via an intraoral approach was performed.Histopathologically,there was a rupture of the fibrous capsule and diffuse cell-rich sheets composed of myoepithelial cells with round nuclei were also seen.Immunohistochemically,the cells that composed of cell rich sheets were positive to smooth muscle actin.Final diagnosis of myoepithelial carcinoma ex pleomorphic adenoma was made.

Importance of microenvironment in preclinical models of breast and prostate cancer

he majority of cancer drugs entering clinical trials fail to reach the market due to poor efficacy. Preclinical efficacy has been traditionally tested using subcutaneous xenograft models that are cheap, fast and easy to perform. However, these models lack the correct tumor microenvironment, leading to poor clinical predictivity. Selecting compounds for clinical trials based on efficacy results obtained from subcutaneous xenograft models may therefore be one important reason for the high failure rates. In this review we concentrate in describing the role and importance of the tumor microenvironment in progression of breast and prostate cancer, and describe some breast and prostate cancer cell lines that are widely used in preclinical studies. We go through different preclinical efficacy models that incorporate the tissue microenvironment and should therefore be clinically more predictive than subcutaneous xenografts. These include three-dimensional cell culture models, orthotopic and metastasis models, humanized and transgenic mouse models, and patient-derived xenografts. Different endpoint measurements and applicable imaging techniques are also discussed. We conclude that models that incorporate the tissue microenvironment should be increasingly used in preclinical efficacy studies to reduce the current high attrition rates of cancer drugs in clinical trials.