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Severe COVID-19 disease caused by SARS-CoV-2 is frequently accompanied by dysfunction of the lungs and extrapulmonary organs. However, the organotropism of SARS-CoV-2 and the port of virus entry for systemic dissemination remain largely unknown. We profiled 26 COVID-19 autopsy cases from four cohorts in Wuhan, China, and determined the systemic distribution of SARS-CoV-2. SARS-CoV-2 was detected in the lungs and multiple extrapulmonary organs of critically ill COVID-19 patients up to 67 days after symptom onset. Based on organotropism and pathological features of the patients, COVID-19 was divided into viral intrapulmonary and systemic subtypes. In patients with systemic viral distribution, SARS-CoV-2 was detected in monocytes, macrophages, and vascular endothelia at blood–air barrier, blood–testis barrier, and filtration barrier. Critically ill patients with long disease duration showed decreased pulmonary cell proliferation, reduced viral RNA, and marked fibrosis in the lungs. Permanent SARS-CoV-2 presence and tissue injuries in the lungs and extrapulmonary organs suggest direct viral invasion as a mechanism of pathogenicity in critically ill patients. SARS-CoV-2 may hijack monocytes, macrophages, and vascular endothelia at physiological barriers as the ports of entry for systemic dissemination. Our study thus delineates systemic pathological features of SARS-CoV-2 infection, which sheds light on the development of novel COVID-19 treatment.

The cardiometabolic index (CMI) is a marker for evaluating visceral adipose distribution and lipid metabolism. This index is useful for detecting metabolic diseases as well as some cardiovascular diseases. The link between the CMI and heart disease among elderly and middle-aged individuals has yet to be fully explored. This study aimed to investigate the relationship between the CMI and heart disease incidence in individuals aged 45 and over. A total of 987 participants aged 45 years and above were enrolled. Only patients without heart disease at baseline were included in the 15-year observation. The CMI was calculated by multiplying the ratio of triglycerides to high-density lipoprotein cholesterol by the waist‒to-height ratio. Participants were then grouped into CMI tertiles. The Kruskal‒Wallis H test and Cox regression analysis were performed. Longitudinal/panel data mixed-effects linear regression models were applied to analyze the relationships between the CMI and nonspecific inflammatory markers. In the highest tertile, there was a 1.60-fold increased risk of coronary heart disease (CHD) after adjusting for age and sex. There was also a positive association between time-varying CMI and hs-CRP. These findings suggest that a higher CMI is related to inflammatory processes and elevated CHD risk, thus highlighting its potential role as a marker for CHD in elderly and middle-aged Chinese individuals.

The purpose of this review is to stress the complicated interactions between the microbiota and the development of heart failure. Moreover, the feasibility of modulating intestinal microbes and metabolites as novel therapeutic strategies is discussed. This study was based on data obtained from PubMed up to March 31, 2019. Articles were selected using the following search terms: \"gut microbiota,\" \"heart failure,\" \"trimethylamine N-oxide (TMAO),\" \"short-chain fatty acid (SCFA),\" \"bile acid,\" \"uremic toxin,\" \"treatment,\" \"diet,\" \"probiotic,\" \"prebiotic,\" \"antibiotic,\" and \"fecal microbiota transplantation.\" Accumulated evidence has revealed that the composition of the gut microbiota varies obviously in people with heart failure compared to those with healthy status. Altered gut microbial communities contribute to heart failure through bacterial translocation or affecting multiple metabolic pathways, including the trimethylamine/TMAO, SCFA, bile acid, and uremic toxin pathways. Meanwhile, modulation of the gut microbiota through diet, pre/probiotics, fecal transplantation, and microbial enzyme inhibitors has become a potential therapeutic approach for many metabolic disorders. Specifically, a few studies have focused on the cardioprotective effects of probiotics on heart failure. The composition of the gut microbiota in people with heart failure is different from those with healthy status. A reduction in SCFA-producing bacteria in patients with heart failure might be a notable characteristic for patients with heart failure. Moreover, an increase in the microbial potential to produce TMAO and lipopolysaccharides is prominent. More researches focused on the mechanisms of microbial metabolites and the clinical application of multiple therapeutic interventions is necessarily required.

Background and purposeAlthough inflammation has been proposed to be a candidate risk factor for cerebral small vessel disease (CSVD), previous findings remain largely inconclusive and vary according to disease status and study designs. The present study aimed to investigate possible associations between inflammatory biomarkers and MRI markers of CSVD.MethodsA group of 15 serum inflammatory biomarkers representing a variety of those putatively involved in the inflammatory cascade was grouped and assessed in a cross-sectional study involving 960 stroke-free subjects. The biomarker panel was grouped as follows: systemic inflammation (high-sensitivity C reactive protein (hsCRP), interleukin 6 and tumour necrosis factor α), endothelial-related inflammation (E-selectin, P-selectin, intercellular adhesion molecule 1, vascular cell adhesion molecule 1 (VCAM-1), CD40 ligand, lipoprotein-associated phospholipase A2, chitinase-3-like-1 protein and total homocysteine (tHCY)) and media-related inflammation (matrix metalloproteinases 2, 3 and 9, and osteopontin). The association(s) between different inflammatory groups and white matter hyperintensity (WMH), lacunes, cerebral microbleeds (CMBs), enlarged perivascular space (PVS) and the number of deep medullary veins (DMVs) were investigated.ResultsHigh levels of serum endothelial-related inflammatory biomarkers were associated with both increased WMH volume (R2=0.435, p=0.015) and the presence of lacunes (R2=0.254, p=0.027). Backward stepwise elimination of individual inflammatory biomarkers for endothelial-related biomarkers revealed that VCAM-1 was significant for WMH (β=0.063, p=0.005) and tHCY was significant for lacunes (β=0.069, p<0.001). There was no association between any group of inflammatory biomarkers and CMBs or PVS. Systemic inflammatory biomarkers were associated with fewer DMVs (R2=0.032, p=0.006), and backward stepwise elimination of individual systemic-related inflammatory biomarkers revealed that hsCRP (β=−0.162, p=0.007) was significant.ConclusionWMH and lacunes were associated with endothelial-related inflammatory biomarkers, and fewer DMVs were associated with systemic inflammation, thus suggesting different underlying inflammatory processes and mechanisms.

Background Berberine (BBR) is an isoquinoline alkaloid found in the Berberis species. It was found to have protected effects in cardiovascular diseases. Here, we investigated the effect the regulatory function of long noncoding RNAs (lncRNAs) during the treatment of stable coronary heart disease (CHD) using BBR. We performed microarray analyses to identify differentially expressed (DE) lncRNAs and mRNAs between whole blood samples from 5 patients with stable CHD taking BBR and 5 no BBR volunteers. DE lncRNAs and mRNAs were validated by quantitative real-time PCR. Results A total of 1703 DE lncRNAs and 912 DE mRNAs were identified. Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated DE mRNAs might be associated with mammalian target of rapamycin and mitogen-activated protein kinase pathway. These pathways may be involved in the healing process after CHD. To study the relationship between mRNAs encoding transcription factors (DNA damage inducible transcript 3, sal-like protein 4 and estrogen receptor alpha gene) and CHD related de mRNAs, we performed protein and protein interaction analysis on their corresponding proteins. AKT and apoptosis pathway were significant enriched in protein and protein interaction network. BBR may affect downstream apoptosis pathways through DNA damage inducible transcript 3, sal-like protein 4 and estrogen receptor alpha gene. Growth arrest-specific transcript 5 might regulate CHD-related mRNAs through competing endogenous RNA mechanism and may be the downstream target gene regulated by BBR. Verified by the quantitative real-time PCR, we identified 8 DE lncRNAs that may relate to CHD. We performed coding and non-coding co-expression and competing endogenous RNA mechanism analysis of these 8 DE lncRNAs and CHD-related DE mRNA, and predicted their subcellular localization and N 6 -methyladenosine modification sites. Conclusion Our research found that BBR may affect mammalian target of rapamycin, mitogen-activated protein kinase, apoptosis pathway and growth arrest-specific transcript 5 in the process of CHD. These pathways may be involved in the healing process after CHD. Our research might provide novel insights for functional research of BBR.

To review the latest progress on the pathogenic mechanism and management of rheumatoid arthritis (RA)-associated coronary artery disease (CAD), and propose advice on future management optimization as well as prospects for research and development of new therapeutic regimen. This study was based on data obtained from PubMed up to May 2019 using various search terms and their combinations, including coronary artery disease, myocardial ischemia, cardiovascular diseases, RA, rheumatic diseases, treatment, therapy, strategies, immunotherapy, inflammation, and anti-inflammation. All retrieved literature was scrutinized, most relevant articles about the pathogenic mechanism and clinical management, especially anti-inflammatory therapy of RA-associated CAD were reviewed. RA is an immune-mediated chronic inflammatory disease which has a great social disease burden. In addition to typical arthritic manifestations, RA also affects extra-articular tissues and organs, within which the involvement of the cardiovascular system, especially incorporating CAD, is the leading cause of death for patients with RA. Recently, numerous basic and clinical studies have been carried out on the mechanism of CAD development and progression under the inflammatory cascade of RA. The effect of traditional RA drugs on CAD risk management has been gradually clarified, and more emerging biologic agents are being explored and studied, which have also achieved satisfactory outcomes. Furthermore, with the success of the CANTOS clinical trial, novel anti-inflammatory therapy for the prevention of cardiovascular disease is believed to have a broad prospect. RA is an independent risk factor for CAD, which mainly results from the underlying inflammatory cascade; therefore, anti-inflammatory therapy, especially the emerging novel biologic drugs, is important for CAD management in patients with RA and may also be a promising approach among the general population.

Background Rare disease patients often experience diagnosis delays or misdiagnosis, which may be due to lack of knowledge on rare diseases among physicians. Objective To assess Chinese physicians’ knowledge on specific rare diseases and identify its associated factors. Methods Thirty-four patient organizations with a unique disease of interest were invited to develop 3 knowledge questions for each rare disease to assess physicians’ knowledge on the disease that they felt most experienced in. The total knowledge score for each participant ranged from a score of 0 to 3. A national cross-sectional study conducted in a cohort of 3197 physicians from 6 provinces across western, central and eastern China. The demographic information of the participants was collected including gender, age, birthplace, income, education, hospital class, working title, working years, and specialty. A multiple linear regression analysis was performed to assess the independent associations between the physician variables and the total knowledge score. Results Two thousand, one hundred and fifteen (66.16%) of the involved physicians obtained a total knowledge score of 2 or 3. The median knowledge scores of 10 (29.4%) rare diseases were a score of 1.5 or below. Physicians with female gender (β = 0.08, p  < 0.05 for females vs. males), and a monthly income of 5000–10,000 RMB (β = 0.11, p  < 0.01 for 5000–10,000 vs. < 5000) and 10,000–30,000 RMB (β = 0.14, p  < 0.05) were associated with a higher score. Specialties of physicians who received a relatively higher score included internal medicine, obstetrics and gynecology, radiology, intensive care unit, and surgery. Conclusions Almost two thirds of the participants had an average or good level of knowledge on the specific rare disease that they felt most experienced in. Physicians with female gender, a monthly income of 5000–10,000 RMB and 10,000–30000 RMB, and specialties of internal medicine, obstetrics and gynecology, radiology, intensive care unit, and surgery, were associated with a relatively higher knowledge score.

Brain glymphatic dysfunction is critical in neurodegenerative processes. While animal studies have provided substantial insights, understandings in humans remains limited. Recent attention has focused on the non‐invasive evaluation of brain glymphatic function. However, its association with brain parenchymal lesions in large‐scale population remains under‐investigated. In this cross‐sectional analysis of 1030 participants (57.14 ± 9.34 years, 37.18% males) from the Shunyi cohort, we developed an automated pipeline to calculate diffusion‐weighted image analysis along the perivascular space (ALPS), with a lower ALPS value indicating worse glymphatic function. The automated ALPS showed high consistency with the manual calculation of this index (ICC = 0.81, 95% CI: 0.662–0.898). We found that those with older age and male sex had lower automated ALPS values (β = −0.051, SE = 0.004, p < .001, per 10 years, and β = −0.036, SE = 0.008, p < .001, respectively). White matter hyperintensity (β = −2.458, SE = 0.175, p < .001) and presence of lacunes (OR = 0.004, 95% CI < 0.002–0.016, p < .001) were significantly correlated with decreased ALPS. The brain parenchymal and hippocampal fractions were significantly associated with decreased ALPS (β = 0.067, SE = 0.007, p < .001 and β = 0.040, SE = 0.014, p = .006, respectively) independent of white matter hyperintensity. Our research implies that the automated ALPS index is potentially a valuable imaging marker for the glymphatic system, deepening our understanding of glymphatic dysfunction. We evaluated the glymphatic system function in the brain using a non‐invasive method, calculation of automated diffusion‐weighted image analysis along the perivascular space (ALPS) index, and found that dysfunction of the glymphatic system potentially influences both vascular and degenerative brain parenchymal lesions in a community‐dwelling cohort.

Background To investigate the epidemiology and in-hospital mortality of veno-venous (VV) and veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) in Mainland China throughout 2018. Methods Patients supported by ECMO from 1700 tertiary hospitals in 31 provinces from January 1 to December 31, 2018, were selected from the National Clinical Improvement System database. Results The 1700 included hospitals had 2073 cases of ECMO in 2018, including 714 VV and 1359 VA ECMOs. The average patient age was 50 years (IQR 31–63), and 1346 were male. The average hospital stay was 17 days (IQR 7–30), and the average costs per case was $36,334 (IQR 22,547–56,714). The three provinces with the highest number of ECMO cases were Guangdong, Beijing, and Zhejiang; the southeast coastal areas and regions with higher GDP levels had more cases. Overall in-hospital mortality was 29.6%. Mortality was higher among patients who were male, over 70 years old, living in underdeveloped areas, and who were treated during the summer. Mortality in provinces with more ECMO cases was relatively low. The co-existence of congenital malformations, blood system abnormalities, or nervous system abnormalities increased in-hospital mortality. Conclusions Mortality and medical expenses of ECMO among patients in China were relatively low, but large regional and seasonal differences were present. Risk factors for higher in-hospital mortality were older age, male sex, in underdeveloped areas, and treatment during the summer. Additionally, congenital malformations and blood system and nervous system abnormalities were associated with in-hospital mortality.

Background Intracranial artery stenosis (ICAS) and cerebral small vessel disease (CSVD) are associated with a heavy socioeconomic burden; however, their longitudinal changes remain controversial. Methods We conducted a longitudinal analysis on 756 participants of Shunyi Cohort who underwent both baseline and follow-up brain magnetic resonance imaging (MRI) and MR angiography in order to investigate the risk factors for ICAS and CSVD progression in community population. Incident ICAS was defined as new stenosis occurring in at least one artery or increased severity of the original artery stenosis. CSVD markers included lacunes, cerebral microbleeds (CMB), and white matter hyperintensities (WMH). Results After 5.58 ± 0.49 years of follow-up, 8.5% of the 756 participants (53.7 ± 8.0 years old, 65.1% women) had incident ICAS. Body mass index (BMI) (OR = 1.09, 95% CI = 1.01–1.17, p  = 0.035) and diabetes mellitus (OR = 2.67, 95% CI = 1.44–4.93, p  = 0.002) were independent risk factors for incident ICAS. Hypertension was an independent risk factor for incident lacunes (OR = 2.12, 95% CI = 1.20–3.77, p  = 0.010) and CMB (OR = 2.32, 95% CI = 1.22–4.41, p  = 0.011), while WMH progression was primarily affected by BMI (β = 0.108, SE = 0.006, p  = 0.002). A higher LDL cholesterol level was found to independently protect against WMH progression (β = −0.076, SE = 0.027, p  = 0.019). Conclusions Modifiable risk factor profiles exhibit different in patients with ICAS and CSVD progression. Controlling BMI and diabetes mellitus may help to prevent incident ICAS, and antihypertensive therapy may conduce to mitigate lacunes and CMB progression. LDL cholesterol may play an inverse role in large arteries and small vessels.