Epidemiology, Pathophysiology, and Imaging of Atherosclerotic Intracranial Disease.

Intracranial atherosclerotic disease (ICAD) is one of the most common causes of stroke worldwide. Among people with stroke, those of East Asia descent and non-White populations in the United States have a higher burden of ICAD-related stroke compared with Whites of European descent. Disparities in the prevalence of asymptomatic ICAD are less marked than with symptomatic ICAD. In addition to stroke, ICAD increases the risk of dementia and cognitive decline, magnifying ICAD societal burden. The risk of stroke recurrence among patients with ICAD-related stroke is the highest among those with confirmed stroke and stenosis ≥70%. In fact, the 1-year recurrent stroke rate of >20% among those with stenosis >70% is one of the highest rates among common causes of stroke. The mechanisms by which ICAD causes stroke include plaque rupture with in situ thrombosis and occlusion or artery-to-artery embolization, hemodynamic injury, and branch occlusive disease. The risk of stroke recurrence varies by the presumed underlying mechanism of stroke, but whether techniques such as quantitative magnetic resonance angiography, computed tomographic angiography, magnetic resonance perfusion, or transcranial Doppler can help with risk stratification beyond the degree of stenosis is less clear. The diagnosis of ICAD is heavily reliant on lumen-based studies, such as computed tomographic angiography, magnetic resonance angiography, or digital subtraction angiography, but newer technologies, such as high-resolution vessel wall magnetic resonance imaging, can help distinguish ICAD from stenosing arteriopathies.

Central arterial stiffening and intracranial atherosclerosis: the atherosclerosis risk in communities neurocognitive study (ARIC-NCS): Aortic stiffness & intracranial atherosclerosis.

OBJECTIVES: Previous studies suggest an association between central arterial stiffness (CAS) and intracranial atherosclerotic disease (ICAD) among Asian participants with stroke or hypertension; this association has not been evaluated in United States populations. We assessed the cross-sectional association of CAS with ICAD presence and burden in late-life, and differences in association by age, sex, and race. MATERIALS AND METHODS: We conducted a cross-sectional analysis of 1,285 Atherosclerosis Risk in Communities Study participants [mean age 75 (standard deviation: 5) years, 38 % male, 20  % Black] at Visit 5 (2011-2013). CAS was measured as carotid-femoral pulse wave velocity (cfPWV) using the Omron VP-1000 Plus. ICAD was assessed using high-resolution vessel wall MRI and MR angiography. We evaluated associations of a 1 standard deviation (SD) cfPWV (3.02 m/s) and high vs. non-high cfPWV (≥ 13.57 m/s vs. < 13.57 m/s) with presence of plaques (yes/no) and plaque number (0, 1-2, and >2) using multivariable logistic and ordinal logistic regression models adjusted for covariates. RESULTS: Each one SD greater cfPWV was associated with higher odds of plaque presence (odds ratio (OR)=1.32, 95 % confidence interval (CI): 1.22, 1.43), and an incrementally higher odds of number of plaques (OR 1-2 vs. 0 plaques = 1.21, 95 % CI: 1.10, 1.33; OR >2 vs. 0 plaques = 1.51, 95 % CI: 1.33,1.71). Results suggested differences by race, with greater magnitude associations among Black participants. CONCLUSIONS: CAS was positively associated with ICAD presence and burden; cfPWV may be a useful subclinical vascular measure for identification of individuals who are at high risk for cerebrovascular disease.

Correlated Hybrid DNA Structures Explored by the oxDNA Model.

Thermodynamically, perfect DNA hybridization can be formed between probes and their corresponding targets due to the favorable energy. However, this is not the case dynamically. Here, we use molecular dynamics (MD) simulations based on the oxDNA model to investigate the process of DNA microarray hybridization. In general, correlated hybrid DNA structures are formed, including one probe associated with several targets as well as one target hybrid with multiple probes leading to the target-mediated hybridization. The formation of these two types of correlated structures largely depends on the surface coverage of the DNA microarray. Moreover, DNA sequence, DNA length, and spacer length have an impact on the structural formation. Our findings shed light on the dynamics of DNA hybridization, which is important for the application of DNA microarray.

Chromosome 10q24.32 Variants Associate With Brain Arterial Diameters in Diverse Populations: A Genome-Wide Association Study.

BACKGROUND: Brain arterial diameters (BADs) are novel imaging biomarkers of cerebrovascular disease, cognitive decline, and dementia. Traditional vascular risk factors have been associated with BADs, but whether there may be genetic determinants of BADs is unknown. METHODS AND RESULTS: The authors studied 4150 participants from 6 geographically diverse population-based cohorts (40% European, 14% African, 22% Hispanic, 24% Asian ancestries). Brain arterial diameters for 13 segments were measured and averaged to obtain a global measure of BADs as well as the posterior and anterior circulations. A genome-wide association study revealed 14 variants at one locus associated with global BAD at genome-wide significance (P<5×10-8) (top single-nucleotide polymorphism, rs7921574; ß=0.06 [P=1.54×10-8]). This locus mapped to an intron of CNNM2. A trans-ancestry genome-wide association study meta-analysis identified 2 more loci at NT5C2 (rs10748839; P=2.54×10-8) and AS3MT (rs10786721; P=4.97×10-8), associated with global BAD. In addition, 2 single-nucleotide polymorphisms colocalized with expression of CNNM2 (rs7897654; ß=0.12 [P=6.17×10-7]) and AL356608.1 (rs10786719; ß=-0.17 [P=6.60×10-6]) in brain tissue. For the posterior BAD, 2 variants at one locus mapped to an intron of TCF25 were identified (top single-nucleotide polymorphism, rs35994878; ß=0.11 [P=2.94×10-8]). For the anterior BAD, one locus at ADAP1 was identified in trans-ancestry genome-wide association analysis (rs34217249; P=3.11×10-8). CONCLUSIONS: The current study reveals 3 novel risk loci (CNNM2, NT5C2, and AS3MT) associated with BADs. These findings may help elucidate the mechanism by which BADs may influence cerebrovascular health.

Association of brain arterial diameters with demographic and anatomical factors in a multi-national pooled analysis of cohort studies.

BACKGROUND AND PURPOSE: Brain arterial diameters are markers of cerebrovascular disease. Demographic and anatomical factors may influence arterial diameters. We hypothesize that age, sex, height, total cranial volume (TCV), and persistent fetal posterior cerebral artery (fPCA) correlate with brain arterial diameters across populations. METHODS: Participants had a time-of-flight MRA from nine international cohorts. Arterial diameters of the cavernous internal carotid arteries (ICA), middle cerebral arteries (MCA), and basilar artery (BA) were measured using LAVA software. Regression models assessed the association between exposures and brain arterial diameters. RESULTS: We included 6,518 participants (mean age: 70 ± 9 years; 41% men). Unilateral fPCA was present in 13.2% and bilateral in 3.2%. Larger ICA, MCA, and BA diameters correlated with older age (Weighted average [WA] per 10 years: 0.18 mm, 0.11 mm, and 0.12 mm), male sex (WA: 0.24 mm, 0.13 mm, and 0.21 mm), and TCV (WA: for one TCV standard deviation: 0.24 mm, 0.29 mm, and 0.18 mm). Unilateral and bilateral fPCAs showed a positive correlation with ICA diameters (WA: 0.39 mm and 0.73 mm) and negative correlation with BA diameters (WA: -0.88 mm and -1.73 mm). Regression models including age, sex, TCV, and fPCA explained on average 15%, 13%, and 25% of the ICA, MCA, and BA diameter interindividual variation, respectively. Using height instead of TCV as a surrogate of head size decreased the R-squared by 3% on average. CONCLUSION: Brain arterial diameters correlated with age, sex, TCV, and fPCA. These factors should be considered when defining abnormal diameter cutoffs across populations.

A Novel Window Into Human Vascular Remodeling and Diagnosing Carotid Flow Impairment: The Petro-Occipital Venous Plexus.

Background Adaptive arterial remodeling caused by flow reduction from downstream stenosis has been demonstrated in animal studies. The authors sought to determine whether inward remodeling from downstream stenosis also occurs in humans and is detectable by ex vacuo expansion of the Rektorzik venous plexus (RVP) surrounding the petrous internal carotid artery. Methods and Results The authors analyzed 214 intracranial magnetic resonance imaging examinations that included contrast-enhanced vessel wall imaging. RVP symmetry was qualitatively assessed on vessel wall imaging. RVP thickness (RVPT) was measured on the thicker side if asymmetric or randomly assigned side if symmetric. Maximum stenosis (M1 or intracranial internal carotid artery) was measured. Posterior communicating artery and A1 diameters (>1.0 mm and 1.5 mm, respectively) defined adequate collateral outflow when proximal to the stenosis. Seventy-two patients had stenosis downstream from RVPT measurements. For those without adequate outflow (38 of 72), 95.0% with RVPT ≥1.0 mm had ≥50% stenosis compared with only 5.6% with RVPT <1.0 mm. For these 72 patients, higher RVPT (RVPT ≥1.0 mm versus <1.0 mm) and absent adequate outflow were associated with greater downstream stenosis (P<0.001) using multivariate regression. For patients with downstream stenosis without adequate outflow, asymmetric RVP thickening was associated with greater ipsilateral stenosis (P<0.001, all had ≥46% stenosis) when stenosis was unilateral and greater differences in stenosis between sides (P=0.005) when stenosis was bilateral. Conclusions Inward internal carotid artery remodeling measured by RVPT or RVP asymmetry occurs as downstream stenosis approaches 50%, unless flow is preserved through a sufficiently sized posterior communicating artery or A1, and may serve as a functional measure of substantial flow reduction from downstream stenosis.

Detection of Dolichoectasia and Atherosclerosis by Automated MRA Tortuosity Metrics in a Population-Based Study.

BACKGROUND: Intracranial vessel tortuosity is a key component of dolichoectasia and has been associated with atherosclerosis and adverse neurologic outcomes. However, the evaluation of tortuosity is mainly a descriptive assessment. PURPOSE: To compare the performance of three automated tortuosity metrics (angle metric [AM], distance metric [DM], and distance-to-axis metric [DTA]) for detection of dolichoectasia and presence of segment-specific plaques. STUDY TYPE: Observational, cross-sectional metric assessment. POPULATION: 1899 adults from the general population; mean age = 76 years, female = 59%, and black = 29%. FIELD STRENGTH/SEQUENCE: 3-T, three-dimensional (3D) time-of-flight MRA and 3D vessel wall MRI. ASSESSMENT: Tortuosity metrics and mean luminal area were quantified for designated segments of the internal carotid artery, middle cerebral artery, anterior cerebral artery, posterior cerebral artery, vertebral artery, and entire length of basilar artery (BA). Qualitative interpretations of BA dolichoectasia were assessed based on Smoker's visual criteria. STATISTICAL TESTS: Descriptive statistics (2-sample t-tests, Pearson chi-square tests) for group comparisons. Receiver operating characteristics area under the curve (AUC) for detection of BA dolichoectasia or segment-specific plaque. Model inputs included 1) tortuosity metrics, 2) mean luminal area, and 3) demographics (age, race, and sex). RESULTS: Qualitative dolichoectasia was identified in 336 (18%) participants, and atherosclerotic plaques were detected in 192 (10%) participants. AM-, DM-, and DTA-calculated tortuosity were good individual discriminators of basilar dolichoectasia (AUCs: 0.76, 0.74, and 0.75, respectively), with model performance improving with the mean lumen area: (AUCs: 0.88, 0.87, and 0.87, respectively). Combined characteristics (tortuosity and mean luminal area) identified plaques with better performance in the anterior (AUCs ranging from 0.66 to 0.78) than posterior (AUCs ranging from 0.54 to 0.65) circulation, with all models improving by the addition of demographics (AUCs ranging from 0.62 to 0.84). DATA CONCLUSION: Quantitative vessel tortuosity metrics yield good diagnostic accuracy for the detection of dolichoectasia. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

Concurrent measurement of perfusion parameters related to small blood vessels and cerebrospinal fluid circulation in the human brain using dynamic dual-spin-echo perfusion MRI.

Accumulating evidence from recent studies has indicated the importance of studying the interaction between the microvascular and lymphatic systems in the brain. To date, most imaging methods can only measure blood or lymphatic vessels separately, such as dynamic susceptibility contrast (DSC) MRI for blood vessels and DSC MRI-in-the-cerebrospinal fluid (CSF) (cDSC MRI) for lymphatic vessels. An approach that can measure both blood and lymphatic vessels in a single scan offers advantages such as a halved scan time and contrast dosage. This study attempts to develop one such approach by optimizing a dual-echo turbo-spin-echo sequence, termed "dynamic dual-spin-echo perfusion (DDSEP) MRI". Bloch simulations were performed to optimize the dual-echo sequence for the measurement of gadolinium (Gd)-induced blood and CSF signal changes using a short and a long echo time, respectively. The proposed method furnishes a T1-dominant contrast in CSF and a T2-dominant contrast in blood. MRI experiments were performed in healthy subjects to evaluate the dual-echo approach by comparing it with existing separate methods. Based on simulations, the short and long echo time were chosen around the time when blood signals show maximum difference between post- and pre-Gd scans, and the time when blood signals are completely suppressed, respectively. The proposed method showed consistent results in human brains as previous studies using separate methods. Signal changes from small blood vessels occurred faster than from lymphatic vessels after intravenous Gd injection. In conclusion, Gd-induced signal changes in blood and CSF can be detected simultaneously in healthy subjects with the proposed sequence. The temporal difference in Gd-induced signal changes from small blood and lymphatic vessels after intravenous Gd injection was confirmed using the proposed approach in the same human subjects. Results from this proof-of-concept study will be used to further optimize DDSEP MRI in subsequent studies.

Two Different Ways of Stress Release in Supercoiled DNA Minicircles under DNA Nick.

It is generally believed that DNA nick is an effective way to release stress in supercoiled DNA, resulting from the twisting motion that individual strands rotate around the axis of the DNA helix. Here, we use MD simulations based on the oxDNA model to investigate the relaxation of 336 bp supercoiled minicircular DNA under DNA nick. Our simulations show that stress release, characterized by the abrupt decrease in linking number, may be induced by two types of DNA motion depending on the nick position. Except for the twisting motion, there is a writhing motion, that is, double strands collectively rotating with one plectoneme removal, which may occur in the process of DNA relaxation with the nick position in the loop region. Moreover, the writhing motion is more likely to occur in the DNA with relatively high hardness, such as C-G pairs. Our simulation results uncover the relationship between structural transformation, stress release, and DNA motion during the dynamic process under DNA nick, indicating the influence of nick position on the relaxation of the supercoiled DNA.

Association of leisure-time physical activity and sedentary behavior with carotid atherosclerosis morphology: The ARIC carotid-MRI study.

Objective: We evaluated the prospective association of midlife leisure-time physical activity (LTPA) and sedentary behavior (SB), and their temporal patterns, with MRI-measured carotid atherosclerotic morphology. Methods: Participants enrolled in the Carotid MRI substudy (2004-2006) of the Atherosclerosis Risk in Communities (ARIC) Study and with self-reported assessments of LTPA and SB at visits 1 (1987-1989) and 3 (1993-1995) were included in this study. LTPA was ascertained using the ARIC/Baecke physical activity questionnaire and categorized according to the American Heart Association's metric of poor, intermediate, or ideal physical activity. SB, measured as TV viewing frequency, was categorized as high, medium, and low. We used multivariable adjusted linear and logistic regression models to examine the associations between midlife (visit 3 only) and persistent (visit 1 to 3) LTPA and TV viewing with carotid artery plaque burden and components. Results: Among the 1,582 (mean age: 59 years, 43% male, 18% Black) participants, 45.7%, 21.7%, and 32.6% reported ideal, intermediate, or poor LTPA, respectively. High TV viewing was reported in 33.8% of participants, with 46.4% and 19.8% reporting medium or low TV viewing, respectively. Compared to poor LTPA, ideal LTPA in midlife was not associated with total wall volume (ß=0.01, 95% CI: -0.01, 0.03), maximum carotid wall thickness (ß=0.06, 95% CI: -0.08, 0.21), normalized wall index (ß=-0.01, 95% CI: -0.03, 0.01), or maximum stenosis (ß=-0.11, 95% CI: -1.98, 1.76). Low or middle, compared to high, TV viewing was also not associated with carotid artery measures of plaque burden. Compared to poor LTPA or high TV viewing, ideal LTPA (odds ratio (OR): 0.82, 95% CI: 0.55, 1.23) and low TV viewing (OR=0.90, 95% CI: 0.56, 1.44) was not associated with odds of lipid core presence, respectively. Conclusion: Overall, this study does not provide strong evidence for an association between LTPA and SB with carotid plaque measures.

Chromosome 10q24.32 Variants Associate with Brain Arterial Diameters in Diverse Populations: A Genome-Wide Association Study.

Background: Brain arterial diameters are novel imaging biomarkers of cerebrovascular disease, cognitive decline and dementia. Traditional vascular risk factors have been associated with brain arterial diameters but whether there may be genetic determinants of brain arterial diameters is unknown. Results: We studied 4150 participants from six geographically diverse population-based cohorts (40% European, 14% African, 22% Hispanic, 24% Asian ancestries). We measured brain arterial diameters for 13 segments and averaged them to obtain a global measure of brain arterial diameters as well as the posterior and anterior circulations. A genome-wide association study (GWAS) revealed 14 variants at one locus associated with global brain arterial diameter at genome-wide significance (P<5×10-8) (top SNP, rs7921574; ß =0.06, P=1.54×10-8). This locus mapped to an intron of CNNM2. A trans-ancestry GWAS meta-analysis identified two more loci at NT5C2 (rs10748839; P=2.54×10-8) and at AS3MT (rs10786721; P=4.97×10-8), associated with global brain arterial diameter. In addition, two SNPs co-localized with expression of CNNM2 (rs7897654, ß=0.12, P=6.17×10-7) and AL356608.1 (rs10786719, ß =-0.17, P=6.60×10-6) in brain tissue. For the posterior brain arterial diameter, two variants at one locus mapped to an intron of TCF25 were identified (top SNP, rs35994878; ß =0.11, P=2.94×10-8). For the anterior brain arterial diameter, one locus at ADAP1 was identified in trans-ancestry genome-wide association analysis (rs34217249; P=3.11×10-8). Conclusion: Our study reveals three novel risk loci (CNNM2, NT5C2 and AS3MT) associated with brain arterial diameters. Our finding may elucidate the mechanisms by which brain arterial diameters influence the risk of stroke and dementia.

The incidence of artificial stone-related silicosis among interior decoration workers in different countries / 中华劳动卫生职业病杂志

In this paper, 177 cases of artificial stone-related silicosis in interior decoration workers from Israel, Spain, USA, Italy and Australia were analyzed. Interior decoration workers were from small businesses (or workshops), engaged in kitchen and/or bathroom artificial stone countertops cutting, grinding, polishing and other reprocessing. In the working environment, the content of crystalline silica in artificial stone was more than 70%, and the concentration of silica dust exceeded the relevant standards. Most workplaces used dry cutting without ventilation and dust removal and other dust-proof measures, and most workers did not wear qualified respiratory protective equipment. Taking comprehensive measures such as wet operation, ventilation and dust removal, and individual protection can effectively prevent the occurrence of artificial stone-related silicosis.

Clinical characteristics and follow-up analysis of 12 patients of acute phosphine poisoning / 中华劳动卫生职业病杂志

Objective: To investigate the clinical characteristics of patients with acute phosphine poisoning, and to follow up and evaluate the prognosis of patients. Methods: In May 2022, 12 patients with phosphine poisoning by respiratory inhalation in Beijing Chao-Yang Hospital of Capital Medical University were analyzed. The patients were treated with symptomatic support therapy. Three months later, patients were re-evaluated the symptoms of poisoning, pulmonary function and magnetic resonance imaging (MRI) of the brain to understand the prognosis of the phosphine poisoning. Results: The main symptoms of 12 patients were respiratory and central nervous system symptoms with hypoxia. The symptoms of poisoning improved after treatment. Follow-up found that the patients had different degrees of residual symptoms. Pulmonary function showed increased airway resistance. Airway challenge test was positive in some patients. MRI of the head of some patients showed small ischemic focus in bilateral frontal lobes. Conclusion: Acute phosphine poisoning may cause persistent damage to the respiratory system and central system, and residual symptoms after 3 months.

A systematic review of the epidemiology and clinical characteristics of artificial stone-related silicosis and dust protection / 中华劳动卫生职业病杂志

Objective: To investigate the epidemiology, clinical characteristics, on-site dust monitoring and individual protection of the patients with artificial stone-related silicosis. Methods: In March 2022, the literature on artificial stone-related silicosis published from January 1965 to February 2022 was searched in China Journal Full-text Database, Wanfang Database, VIP Database, EMbase and PubMed. Chinese and English search terms include "silica dust""silica dust""silicosis""artificial stone""pneumoconiosis", etc. References were included according to inclusion and exclusion criteria, and data were extracted. The epidemiological characteristics, natural course of disease, workplace dust concentration and individual protection level of patients with artificial stone-related silicosis were analyzed by systematic review. Results: A total of 30 literatures were included, including 7 cohort studies, 14 cross-sectional studies, 3 case-control studies and 6 case reports. A total of 1358 patients with artificial stone-related silicosis were diagnosed from 1997 to 2020, with an average age of 41.5 years old and an average dust exposure time of 11.3 years. Among them, 36.2% (282/778) had progressive mass fibrosis or accelerated progressive silicosis at first diagnosis. Chest imaging showed diffuse small nodule shadow, pulmonary fibrosis, and silico-alveolar proteinosis. Pulmonary function showed restricted or mixed ventilation disorder with or without decreased diffusion volume. The disease progressed rapidly, with progressive mass fibrosis, respiratory failure, and even death. Patients engaged in artificial quartz stone processing, with high concentration of silica including ultra-fine particles, most of which were dry operation, lack of on-site ventilation measures and no effective personal protection. Conclusion: The artificial stone processing workers suffer from artificial stone-related silicosis due to dry cutting, lack of on-site dust removal facilities and personal protective measures, and the disease progresses rapidly, leading to poor prognosis.

A concise review of diagnosis and evaluation of interstitial lung abnormalities / 中华劳动卫生职业病杂志

Interstitial lung abnormalities (ILAs) refer to the subtle or mild signs of ILAs pulmonary parenchyma on chest HRCT scans, which are not yet sufficient to diagnose a certain interstitial lung disease, may be potentially compatible an early stage of the diseases. The signs of ILAs usually includes ground-glass opacities, reticular abnormakicies, honeycombing, traction bronchiectasis or non-emphysematous cysts. This article reviews the research progreses in the definition and classification, risk factors, prognosis, comorbidities and management of ILAs in combination with domestic and foreign literatures.

Mechanism of Banxia Baizhu Tianma decoction to prevent the development of prehypertension and excessive phlegm-dampness syndrome in rats based on metabonomics technology / 药学学报

The alterations of serum biological endogenous chemicals in rats with phlegm dampness accumulation syndrome of prehypertension (PHT) were interfered by Banxia Baizhu Tianma decoction (BBT), and the metabolic regulatory pathway of BBT was clarified using serum metabonomics analysis. To replicate the rat model of prehypertension phlegm dampness syndrome, blood pressure, behavioral markers, and serum biochemical markers of rats were collected. BBT's effectiveness in controlling blood pressure and blood lipids was assessed, and changes in endogenous small molecules in rat serum were determined using UPLC-Q-Orbitrap MS metabolic analysis. The results showed that BBT could regulate 9 metabolites, including arachidonic acid, cholic acid, glycodeoxycholic acid, N-adenosyltyrosine, arginine, lysophosphatidylethanolamine (20:0/0:00), lysophospholipid (P-18:0), lysophospholipid (18:0), lysophospholipid (22:5(7Z,10Z,13Z,16Z,19Z)). MetaboAnalyst was used to analyze the metabolic pathway. There were 7 metabolic pathways closely related to the change of blood pressure in rats, among which arachidonic acid metabolic pathway was the most critical. The metabolism difference foreign body in the model rats tends to return to the normal level, which provides a research basis for the mechanism of BBT from the perspective of metabonomics. This study was approved by the Experimental Animal Welfare Ethics Review Committee of Shandong University of Traditional Chinese Medicine (approval number: SDUTCM20211103001).

[Influence of electroacupuncture of"Zusanli"(ST36)on mast cells/TRPV1 signaling pathway in visceral hypersensitivity rats with functional dyspepsia].

OBJECTIVE: To explore the interventional mechanism of electroacupuncture (EA) of "Zusanli"(ST36)based on the involvement of mast cells/ transient receptor potential vanilloid type1 (TRPV1) signaling pathway in relieving visceral hypersensitivity in functional dyspepsia (FD) rats. METHODS: Sixty SD rats (half male and half female, 10 days in age) were randomly divided into normal control, model, medication (ketotifen) and EA groups, with 15 rats in each group. The FD model was established by gavage of iodoacetamide combined with tail clamping (stress stimulation). Rats of the medication group received intraperitoneal injection of ketotifen (1 mg·kg-1·d-1) for 14 d, and those of the EA group received EA of ST36 for 20 min, once a day for 14 d. An air-balloon was inserted into the rat's stomach for recording changes of the intragastric pressure (mL/mm Hg) via a pressure transducer. The visceral hypersensitivity was assessed using abdominal withdrawal reflex (AWR) score and the number and degranulation of mast cells of gastric mucosa were observed using toluidine blue staining. The expression levels of TRPV1 and proteinase activated receptor 2 (PAR2) in the stomach were observed using immunofluorescence histochemistry and Western blot, separately, and the contents of SP and CGRP in the stomach detected using ELISA. RESULTS: When the intragastric pressure was at 50, 60 and 70 mm Hg, the gastric compliance was significantly decreased (P<0.01), and the levels of visceral sensitivity increased in the model group （P<0.01）。 TRPV1 immunofluorescence tensity, expression of PAR2 and TRPV1 proteins, and contents of SP and CGRP in the stomach were considerably up-regulated in the model group compared with the normal control group (P<0.01). In comparison with the model group, under intragastric pressure of 50，60 and 70 mm Hg, the gastric compliance was obviously increased, and the visceral hypersensitivity decreased in the EA group （P<0.01,P<0.05）. TRPV1 immunofluorescence intensity, expression levels of PAR2 and TRPV1 proteins, and the contents of SP and CGRP in the stomach were considerably down-regulated in both medication and EA groups compared with the model group (P<0.01, P<0.05). The therapeutic effect of EA was significantly superior to that of medication in up-regulating the gastric compliance （at 70 mm Hg）, and down-regulating the contents of SP and CGRP (P<0.05). No significant differences were found between the EA and medication groups in up-regulating gastric compliance at intragastric pressure of 50 and 60 mm Hg, and in down-regulating the visceral sensitivity, TRPV1 fluorescence intensity, and expression of PAR2 and TRPV1 proteins (P>0.05). Toluidine blue staining showed an apparent increase of mast cell number with obvious degranulation in the gastric mucosa of rats in the model group, which was milder in the EA and medication groups. CONCLUSION: EA of ST36 can suppress visceral hypersensitivity and increase the gastric compliance in FD rats, which may be related with its effects in inhibiting the activation of gastric mast cells, and down-regulating the expression of gastric PAR2 and TRPV1 proteins and SP and CGRP contents.

Non-contrast hemodynamic imaging of Moyamoya disease with MR fingerprinting ASL: A feasibility study.

PURPOSE: MR Fingerprinting (MRF) Arterial Spin Labeling (ASL) is a non-contrast technique to estimate multiple brain hemodynamic and structural parameters in a single scan. The purpose of this study is to examine the feasibility and initial utility of MRF-ASL in Moyamoya disease. METHODS: MRF-ASL, conventional single-delay ASL, Time-of-flight (TOF) MR angiography, and contrast-based dynamic-susceptibility-contrast (DSC) MRI were prospectively collected from a group of Moyamoya patients in North America (N = 21, 4 men and 17 women). Sixteen healthy subjects (7 men and 9 women) also underwent an MRF-ASL scan. Cerebral blood flow (CBF), bolus arrival time (BAT), and tissue T1 were compared between Moyamoya patients and healthy controls. Perfusion parameters from MRF-ASL were compared to those from other MRI sequences. Multi-linear regression was used for comparisons of parameter values between Moyamoya and control groups. Linear mixed-effects models was used when comparing MRF-ASL to PCASL and DSC parameters. Spearman's Rank Correlation Coefficient was calculated when comparing MRF-ASL to and MRA grades. A P value of 0.05 or less was considered significant. RESULTS: BAT in stenotic internal carotid artery (ICA) territories was prolonged (P < 0.001) in Moyamoya patients, when compared with healthy controls. CBF in stenotic ICA territories of Moyamoya patients was not different from CBF in healthy controls; but in the PCA territories, CBF in Moyamoya patients was higher (P < 0.01) than controls. Quantitative T1 values in the stenotic ICA territories was longer (P < 0.05) than that in controls. Hemodynamic parameters estimated from MRF-ASL were significantly correlated with single-delay ASL and DSC. Longer BAT was associated with more severe intracranial artery stenosis in ICA. CONCLUSIONS: MRF-ASL is a promising technique to assess perfusion and structural abnormalities in Moyamoya patients.

Current trends in research on pulmonary fibrosis and metabolites: A bibliometric analysis / 环境与职业医学

Background Certain metabolites are closely related to the occurrence and development of pulmonary fibrosis, and the related mechanism has not been fully elucidated. It is necessary to explore the trends of various metabolites and causes of pulmonary fibrosis. Objective To discuss the trends of publication and research hotspots of pulmonary fibrosis-related metabolites by bibliometrics. Methods With "pulmonary fibrosis" and "metabolites" in both Chinese and English as primary keywords, literature search was conducted through public online databases: PubMed, Web of Science, SinoMed, and CNKI. NoteExpress 3.0 and Excel 2019 were used to store and organize the collected literature. Analyses included publication year, number of papers, institution, country/region, and journal title. VOSviewer 1.6.10 was used for visual analysis. Keyword co-occurrence was analyzed by setting the minimum threshold for the occurrence of keywords to 5 times. Results The research on pulmonary fibrosis and associated metabolites in foreign language was earlier than that in Chinese language. Since the 1990s, the number of literature showed an increasing trend in both foreign and Chinese language literature. A total of 1 062 articles were published in foreign languages, of which 864 articles contained the authors’ address information. The authors in the United States published 340 articles, followed by China with 196 articles, and then Japan, Germany, and Italy. There were 728 relevant pieces of literature published in Chinese, 709 of which included the authors’ institution information and 350 institutions were involved. North China University of Science and Technology, Shanxi Medical University, Peking University, Zhengzhou University, China Medical University，and Soochow University were the top 6 by number of publication. A total of 255 Chinese journals published 728 Chinese articles, and among them 242 articles (33.24%) were published by 12 journals having published more than ten articles per journal. A total of 1062 articles were published in 609 foreign language journals, and among them 179 articles (16.85%) were published by 8 journals with more than 15 articles published by each journal. The results of keywords co-occurrence analysis suggested that pulmonary fibrosis in association with glucose metabolism, lipid metabolism, amino acid metabolism, nucleotide metabolism, and biological oxidation were the common themes studied at home and abroad. Conclusion The number of publications on pulmonary fibrosis and metabolites has been on the rise in recent years, and the research hotspots include glucose metabolism, lipid metabolism, amino acid metabolism, nucleotide metabolism, and biological oxidation.

Chest high-resolution CT features analysis in predicting the progression of asbestosis / 中华劳动卫生职业病杂志

Objective: To analyze the radiological characteristics of chest high-resolution computed tomography (HRCT) of patients with asbestosis, and to investigate the signs of predicting the disease progression of asbestosis. Methods: A prospective method was used to enroll 68 patients with asbestosis who were regularly followed up from 2013 to 2016. The radiological characteristics of patients with asbestosis were described by the International Classification of HRCT for Occupational and Environmental Respiratory Diseases (ICOERD) , and the differences between patients with and without progression were compared during the observation period. The Cox proportional hazards regression model was used to analyze the chest HRCT radiological signs predicting the progression of asbestosis. Results: The study included 68 patients with asbestosis aged (65.5±7.8) years old, of which 64.7% (44/68) were female, 29.4% (20/68) had a history of smoking. There was no significant difference in age, sex, smoking and asbestos exposure between patients with progressive asbestosis (20.6%, 14/68) and patients without progressive asbestosis (79.4%, 54/68) (P>0.05) . Chest HRCT of patients with asbestosis showed irregular and/or linear opacities, of which 5.9% (4/68) were accompanied by honeycombing. Irregular and/or linear opacities were mainly lower lung preponderant, often accompanied with ground glass opacity and mosaic perfusion. 98.5% (67/68) had pleural abnormalities, of which 39.7% (27/68) had diffuse pleural thickening with parenchymal bands and/or rounded atelectasis. The analysis of multivariable Cox proportional hazard regression showed that the risk of the progression of asbestosis was increased with higher irregular and/or linears opacities cores (HR=1.184, 95%CI: 1.012-1.384, P=0.034) and the appearance of honeycombing (HR=6.488, 95%CI: 1.447-29.097, P=0.015) . Conclusion: The irregular and/or linear opacities scores and honeycombing on chest HRCT are independent influencing factors for predicting the disease progression of asbestosis.