Publications by authors named "Jian-Jun Li"

661 Publications

NAFLD fibrosis score is correlated with PCSK9 and improves outcome prediction of PCSK9 in patients with chest pain: a cohort study.

Lipids Health Dis 2022 Jan 7;21(1). Epub 2022 Jan 7.

Cardiometabolic medicine center, State Key Laboratory of Cardiovascular Diseases, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No 167 BeiLiShi Road, XiCheng District, Beijing, 100037, China.

Background: The risk of liver fibrosis in non-alcoholic fatty liver disease (NAFLD) can be easily evaluated by noninvasive scoring systems, of which the NAFLD fibrosis score (NFS) is the most commonly used. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a new predictor of cardiovascular events, has been reported to be associated with cardiovascular outcomes and NAFLD. However, the relationship of NFS with PCSK9 and their prognostic abilities in cardiovascular risks are unknown.

Methods: A total of 2008 hospitalized subjects who had chest pain without lipid-lowering therapy were consecutively included. Baseline clinical data were collected, and the NFS was calculated. The circulating PCSK9 concentration was determined by enzyme immunoassay. The major adverse cardiovascular event (MACE) occurrences were recorded in the follow-up period. Associations of PCSK9 concentration with NFS were examined. All of the participants were categorized into three groups according to NFS levels and were further stratified by PCSK9 tertiles to evaluate the MACEs.

Results: 158 (7.87%) MACEs were observed during a mean of 3.2 years of follow-up. NFS levels were independently related to higher PCSK9 levels according to multivariable linear regression analysis. Furthermore, elevated PCSK9 and NFS concentrations were respectively associated with increased MACE incidence in multivariable Cox regression models. When combining NFS status with PCSK9 tertiles as a stratifying factor, patients with intermediate-high NFS and high PCSK9 levels had higher risks of events than those with low NFS and low PCSK9 levels.

Conclusions: This study revealed for the first time that NFS is positively related to PCSK9 and that the combination of NFS and PCSK9 greatly increased the risk of MACEs in patients with chest pain, providing a potential link between NFS and PCSK9 for predicting cardiovascular events.
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http://dx.doi.org/10.1186/s12944-021-01610-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8742334PMC
January 2022

Active Enhancer Assessment by H3K27ac ChIP-seq Reveals Claudin-1 as a Biomarker for Radiation Resistance in Colorectal Cancer.

Dose Response 2021 Oct-Dec;19(4):15593258211058981. Epub 2021 Dec 8.

Department of General Surgery, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P. R. China.

Background: Colorectal cancer (CRC) represents the third most common malignant tumor in the worldwide. Radiotherapy is the common therapeutic treatment for CRC, but radiation resistance is often encountered. ChIP-seq of Histone H3K27 acetylation (H3K27ac) has revealed enhancers that play an important role in CRC. This study examined the relationship between an active CRC enhancer and claudin-1 (CLDN1), and its effect on CRC radiation resistance.

Methods: The target CRC genes of active enhancers were obtained from public H3K27ac ChIP-seq, and the genes highly expressed in radio-resistant CRC were screened and intersected with enhancer-driven genes. The clinical roles of CLDN1 in radiation resistance were examined using the t-test, standard mean deviation (SMD), summary receiver operating characteristic curve and Kaplan-Meier curves. The co-expressed genes of CLDN1 were calculated using Pearson Correlation analysis, and Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes and Gene Set Variation Analysis (GSVA) analyses were used to examine the molecular mechanisms of CLDN1.

Results: Total 13 703 CRC genes were regulated by enhancers using 58 H3K27ac ChIP-seq. Claudin-1 (CLDN1) was enhancer-driven and notably up-regulated in CRC tissues compared to non-CRC controls, with a SMD of 3.45 (95 CI % = .56-4.35). CLDN1 expression was increased in radiation-resistant CRC with a SMD of .42 (95% CI = .16-.68) and an area under the curve of .74 (95% CI = .70-.77). The cell cycle and immune macrophage levels were the most significant pathways associated with CLDN1.

Conclusion: CLDN1 as an enhancer-regulated gene that can boost radiation resistance in patients with CRC.
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http://dx.doi.org/10.1177/15593258211058981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8669133PMC
December 2021

Lipoprotein (a)-mediated vascular calcification: population-based and in vitro studies.

Metabolism 2022 Feb 23;127:154960. Epub 2021 Dec 23.

State Key Laboratory of Cardiovascular Diseases, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No 167 BeiLiShi Road, XiCheng District, Beijing 100037, China. Electronic address:

Background: Lipoprotein (a) [Lp(a)] is a causal risk factor for cardiovascular diseases, while its role in vascular calcification has not been well-established. Here, we investigated an association of Lp(a) with vascular calcification using population-based and in vitro study designs.

Methods: A total of 2806 patients who received coronary computed tomography were enrolled to assess the correlation of Lp(a) with the severity of coronary artery calcification (CAC). Human aortic smooth muscle cells (HASMCs) were used to explore mechanisms of Lp(a)-induced vascular calcification.

Results: In the population study, Lp(a) was independently correlated with the presence and severity of CAC (all p < 0.05). In vitro study showed that cell calcific depositions and alkaline phosphatase (ALP) activity were increased and the expression of pro-calcific proteins, including bone morphogenetic protein-2 (BMP2) and osteopontin (OPN), were up-regulated by Lp(a) stimulation. Interestingly, Lp(a) activated Notch1 signaling, resulting in cell calcification, which was inhibited by the Notch1 signaling inhibitor, DAPT. Lp(a)-induced Notch1 activation up-regulated BMP2-Smad1/5/9 pathway. In contrast, Noggin, an inhibitor of BMP2-Smad1/5/9 pathway, significantly blocked Lp(a)-induced HASMC calcification. Notch1 activation also induced translocation of nuclear factor-κB (NF-κB) accompanied by OPN overexpression and elevated inflammatory cytokines production, while NF-κB silencing alleviated Lp(a)-induced vascular calcification.

Conclusions: Elevated Lp(a) concentrations are independently associated with the presence and severity of CAC and the impact of Lp(a) on vascular calcification is involved in the activation of Notch1-NF-κB and Notch1-BMP2-Smad1/5/9 pathways, thus implicating Lp(a) as a potential novel therapeutic target for vascular calcification.
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http://dx.doi.org/10.1016/j.metabol.2021.154960DOI Listing
February 2022

Relations of physical signs to genotype, lipid and inflammatory markers, coronary stenosis or calcification, and outcomes in patients with heterozygous familial hypercholesterolemia.

J Transl Med 2021 Dec 7;19(1):498. Epub 2021 Dec 7.

Cardiovascular Metabolic Center, State Key Laboratory of Cardiovascular Diseases, Fu Wai Hospital, National Clinical Research Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 BeiLiShi Road, XiCheng District, Beijing, China.

Background: Although the presence of physical signs [tendon xanthomas and/or corneal arcus (TX/CA)], are associated with the risk of coronary artery disease in patients with heterozygous familial hypercholesterolemia (HeFH), their relationship with genotypes and clinical characteristics has not been fully determined. This study aimed to examine the association of TX/CA with genetic mutation, lipid- and inflammation-related markers, the severity of coronary stenosis or calcification, and cardiovascular events (CVEs) in patients with HeFH.

Methods: LDLR, APOB, and PCSK9 genes were screened in 523 HeFH patients, and patients with TX/CA (n = 50) were 1:4 propensity score-matched to patients without TX/CA (n = 200) to adjust for age and sex. Laboratory markers (proprotein convertase subtilisin/kexin type 9 [PCSK9], lipoprotein(a) and high-sensitivity C-reactive protein [hsCRP]), computed tomography angiography, coronary angiography, and follow-up for CVEs were performed.

Results: Patients with physical signs had significantly higher low-density lipoprotein cholesterol levels; higher PCSK9 or hsCRP concentrations; more LDLR positive mutations; and higher prevalence of high tertiles of Gensini, SYNTAX and Jeopardy scores as well as coronary artery calcium scores than did those without. Over an average follow-up of 3.7 years, the incidence of CVEs was significantly higher in patients with TX/CA (log-rank p < 0.001). Patients with physical signs and mutation positivity had threefold higher risks of CVEs (adjusted hazard ratio 3.34, 95% confidence interval 1.04-10.72, p = 0.024).

Conclusions: Physical signs were associated with genotypes and phenotypes, and worse outcomes in patients with HeFH, suggesting that these signs may help in risk stratification in these patients.
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http://dx.doi.org/10.1186/s12967-021-03166-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8650321PMC
December 2021

Retraction Note to: Diffusion-weighted MR imaging of locally advanced breast carcinoma: the optimal time window of predicting the early response to neoadjuvant chemotherapy.

Cancer Imaging 2021 11 25;21(1):62. Epub 2021 Nov 25.

Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, #1838 Guangzhou Avenue North, Guangzhou City, 510,515, Guangdong Province, China.

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http://dx.doi.org/10.1186/s40644-021-00434-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8620256PMC
November 2021

Inhibition of glioblastoma progression by Urolithin A in vitro and in vivo by regulating Sirt1-FOXO1 axis via ERK/AKT signaling pathways.

Neoplasma 2021 Nov 25. Epub 2021 Nov 25.

Department of Psychology, Binzhou Medical University Hospital, Binzhou, Shandong, China.

Glioblastoma (GBM) is the most universal and devastating primary intracranial neoplasm in the central nervous system. Urolithin A (UA) possesses many pharmacological and biological activities, but its function in GBM is not clear. CCK-8 and colony formation test were used to measure the anti-proliferative potency of UA against GBM cells. Flow cytometry was applied to evaluate cell cycle arrest and apoptosis of U251 and U118 MG cells upon UA incubation. Quantitative real-time PCR and western blot were conducted to test the regulatory effect of UA on the expression of Sirt1 and FOXO1. Immunodeficient mice were implanted with GBM cells for in vivo validation of anti-cancer effect of UA. We found UA repressed the proliferation, migration and invasion of glioblastoma cells, while also inhibited the induction of colony formation ability and epithelial to mesenchymal transition (EMT) in a time- or dose-dependent manner. The does-dependent relationship of UA inducing the cell cycle arrest and apoptosis of glioblastoma cells was identified. Furthermore, UA could enhance the expression levels of Sirt1 and FOXO1 and the knockdown of Sirt1 blocked the inhibitory effects of UA on the proliferation and migration of glioblastoma cells, and correspondingly modified the expression level of FOXO1. Overexpression of Sirt1 restored the despaired inhibitory effect of UA induced by Sirt1 knockout on the proliferation and migration of glioblastoma cells. In animal experiments, UA decreased the tumor size and weight of glioblastoma in xenograft nude mice and promoted the expression of Sirt1 and FOXO1 in transplanted tumors. Our findings presented in this study indicate that UA exerts a repressive effect on glioblastoma cells in vivo and in vitro by regulating Sirt1-FOXO1 axis via the ERK and AKT pathways, indicating that UA is a new novel therapeutic candidate for the treatment of glioblastoma.
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http://dx.doi.org/10.4149/neo_2021_210623N834DOI Listing
November 2021

Association of circulating proprotein convertase subtilisin/kexin type 9 concentration, prothrombin time and cardiovascular outcomes: a prospective cohort study.

Thromb J 2021 Nov 22;19(1):90. Epub 2021 Nov 22.

Cardiometabolic Medicine Center, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No 167 BeiLiShi Road, XiCheng District, Beijing, 100037, China.

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is considered to have multiple roles in the development of atherosclerosis, which is recently reported to participate in the thrombotic process. We aimed to examine the relationship between PCSK9 concentration, coagulation indexes and cardiovascular events.

Methods: A total of 2293 consecutive patients with angina-like chest pain and without lipid-lowering drugs treatment were enrolled and followed up for major adverse cardiovascular events (MACEs). Circulating PCSK9 concentration was determined by ELISA. The routine coagulation tests including activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time were performed. The associations between PCSK9 concentration, routine coagulation indicators and MACEs were analyzed.

Results: Patients with high PCSK9 levels had lower PT and APTT levels (all p <  0.05). However, PCSK9 concentration was only independently and negatively correlated with PT (β = - 0.115, p <  0.001). During a mean of 38.3 months, 186 (8.1%) MACEs were occurred. Multiple Cox regression analysis indicated high PCSK9 or low PT levels as risk factors related to MACEs. When the prognosis was analyzed by the combination of PCSK9 and PT levels, patients with high PCSK9 and low PT had higher incidence of MACEs compared to those with low PCSK9 and high PT.

Conclusions: Our study firstly suggested that PCSK9 concentration was negatively correlated with plasma levels of PT. Furthermore, high PCSK9 and low PT were associated with MACEs and the combination of PCSK9 with PT had an addictive effect on predicting cardiovascular outcomes in patients with chest pain, which was useful for further subdivision of cardiovascular risks.
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http://dx.doi.org/10.1186/s12959-021-00344-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8607723PMC
November 2021

Epidemiology and Clinical Characteristics of Henoch-Schönlein Purpura Associated with Epstein-Barr Virus Infection.

Mediterr J Hematol Infect Dis 2021 1;13(1):e2021064. Epub 2021 Nov 1.

Medical department, The first people's Hospital of Guangshui, China.

Background: Henoch-Schönlein purpura (HSP) is an immune-mediated vasculitis, and the formation of immune complexes may be triggered by exposure to Epstein-Barr virus (EBV) infection.

Methods: We performed a five-year case-control study to evaluate the epidemiology and clinical characteristics of HSP associated with EBV infection.

Results: The incidence of EBV-triggered HSP was 4.2%, while EBV infection in children with HSP was 0.9%; The EBV-triggered HSP cases had a significantly higher frequency of abdominal pain than the (MP)-triggered HSP group (χ2 = 8.024, p = 0.005); Significant differences were observed in the duration of abdominal pain (Z = -1.935, = 0.027) between the two groups; C3 (t = 9.709, < 0.001), IgA (t = 20.39, < 0.001) and IgG (t = 6.407, < 0.001) were significantly increased in the EBV infection group than those in the healthy control group. Notably, significantly higher proportion of CD19 (t = 6.773, < 0.001) and lower proportion of CD56 (t = 11.13, < 0.001) was found in EBV infection group compared with healthy control group. The IgA level was higher than that of the non-infectious group (t = 2.162, = 0.032), but their CD4/CD8 ratio (t = 10.070, < 0.001) and CD56 proportion (t = 2.096, = 0.037) were significantly lower.

Conclusions: Both cellular and humoral immunity were involved in the pathogenesis of EBV-triggered HSP, leading to increased production of inflammatory mediators and immunoglobulins. Those events may cause or promote the development of systemic vessel vasculitis.
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http://dx.doi.org/10.4084/MJHID.2021.064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8577555PMC
November 2021

Berberine attenuates atherosclerotic lesions and hepatic steatosis in ApoE mice by down-regulating PCSK9 via ERK1/2 pathway.

Ann Transl Med 2021 Oct;9(20):1517

State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Disease, Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: It has been demonstrated that berberine (BBR), a kind of alkaloid derived from Chinese herbal medicine, has multiple pharmacological effects on human's diseases including anti-atherosclerosis action. However, although the previous studies showed that the beneficial impact of BBR on atherosclerosis might be associated with proprotein convertase subtilisin/kexin type 9 (PCSK9), the exact underlying mechanism are not fully determined. The present study aimed to investigate potential mechanisms of anti-atherosclerosis by BBR using ApoE mice.

Methods: The eight-week mice were divided into five groups: group 1 (wild type C57BL/6J mice with normal diet), group 2 (ApoE mice with normal diet), group 3 [ApoE mice with high-fat diet (HFD)], group 4 (ApoE mice with HFD, and treatment with low dose BBR of 50 mg/kg/d), and group 5 (ApoE mice with HFD, and treatment with high dose BBR of 100 mg/kg/d). After a 16-week treatment, the blood sample, aorta and liver were collected for lipid analysis, hematoxylin-eosin (HE) or oil red O staining, and Western blotting respectively. Besides, HepG2 Cells were cultured and treated with different concentrations of BBR (0, 5, 25 and 50 µg/mL) for 24 hours. Subsequently, cells were collected for real-time PCR or western blotting assays. Finally, the expression levels of PCSK9, LDL receptor (LDLR), ATP-binding cassette transporter A1 (ABCA1), ATP-binding cassette transporter G1 (ABCG1), and scavenger receptor class B type I (SR-BI) were examined.

Results: Fifty mg/kg/d and 100 mg/kg/d of BBR decreased total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) cholesterol (LDL-C), and increased high-density lipoprotein cholesterol (HDL-C) level. Moreover, BBR reduced aorta atherosclerotic plaque, and ameliorated lipid deposition in ApoE mice fed with HFD. Finally, in vitro study showed that BBR promoted intracellular cholesterol efflux, up-regulated LDLR and down-regulated PCSK9 expression via the ERK1/2 pathway in cultured HepG2 cells.

Conclusions: Data indicated that BBR significantly attenuated lipid disorder, reduced aortic plaque formation, and alleviated hepatic lipid accumulation in ApoE mice fed with HFD, which was associated with down-regulation of PCSK9 through ERK1/2 pathway.
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http://dx.doi.org/10.21037/atm-20-8106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8576642PMC
October 2021

Improvement of evaluation in Chinese patients with atherosclerotic cardiovascular disease using the very-high-risk refinement: a population-based study.

Lancet Reg Health West Pac 2021 Dec 21;17:100286. Epub 2021 Oct 21.

State Key Laboratory of Cardiovascular Disease, FuWai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, BeiLiShi Road 167, Beijing 100037, China.

Background: Continuous refinement of atherosclerotic cardiovascular disease (ASCVD) stratification has raised the definition of very-high-risk (VHR) recently, which has been underutilized in China. We aimed to identify patients at VHR and evaluate their performances in a Chinese population.

Methods: A total of 9944 patients with ASCVD was continuously enrolled. Patients at VHR was identified according to 2018 AHA/ACC guideline. Median follow-up was 36.4 months. Clinical characteristics, low-density lipoprotein cholesterol (LDL-C) achievements, and the prognostic value of VHR mapping for cardiovascular events (CVEs) were evaluated.

Findings: Overall, 26% (2542/9944) of patients were deemed as VHR, which were subsequently divided into two subgroups of VHR-1 [31% (779/2542)] and VHR-2 [69% (1763/2542)]. The rates of VHR were higher among patients of male (30%,2157/7268), young with age <45 years (46%,518/1130), and low-income regions (27%, 498/1838). Patients at VHR carried higher rates of risk factors than those at non-VHR (all p<0.001). However, only 3% (80/2542) of patients at VHR were prescribed with high-intensity of statins, and just 13% (321/2542) of them reached the LDL-C goal (<1.4mmol/L). Furthermore, of patients with coronary stenosis (n=9806), multiple-diseased vessels (47%, 1192/2523 36%,2587/7283) and occlusive lesions (36%, 902/2523 13%, 949/7283) were detected more commonly in those at VHR than non-VHR. The adjusted hazard ratios of VHR-1 and VHR-2 for primary CVEs were 2.58(1.61-4.14) and 2.23(1.55-3.20), respectively.

Interpretation: Our study firstly reported that patients at VHR carried more severe ASCVD burden, lower LDL-C achievement, and higher CVEs risk, suggesting that the refinement of ASCVD might be considered in China to further understand patients at VHR.

Funding: Capital Health Development Fund and CAMS Major Collaborative Innovation Project.
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http://dx.doi.org/10.1016/j.lanwpc.2021.100286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8551815PMC
December 2021

Association of diabetes mellitus with clinical outcomes in patients with different coronary artery stenosis.

Cardiovasc Diabetol 2021 10 23;20(1):214. Epub 2021 Oct 23.

State Key Laboratory of Cardiovascular Disease, National Clinical Research Center for Cardiovascular Diseases, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No 167 BeiLiShi Road, XiCheng District, Beijing, 100037, China.

Background: It has been demonstrated that patients with type 2 diabetes mellitus (DM) is associated with increased cardiovascular risk. However, little is known regarding the long-term prognosis in diabetic patients who experience mild-to-intermediate coronary artery stenosis (CAS). This study was to assess the clinical outcomes of diabetic patients with different severity of CAS.

Methods: We consecutively enrolled 10,940 patients hospitalized due to angina-like chest pain and followed up for major adverse cardiovascular events (MACEs) covering cardiac death, myocardial infarction, ischemic stroke, unplanned coronary revascularization and angina-related hospitalization. According to coronary angiography, patients were divided into non-obstructive CAS (NOCAS, < 50% stenosis), intermediate CAS (ICAS, 50-69% stenosis), and severe CAS (SCAS, 70-100% stenosis) subgroups, and were further categorized into six groups as NOCAS with DM and non-DM, ICAS with DM and non-DM, and SCAS with DM and non-DM.

Results: During a median follow-up of 40 months, 1,017 (11.1%) MACEs occurred. In patients with ICAS or SCAS, the incidence of events was higher when patients coexisted with DM (p < 0.05, respectively). In subgroup analyses, patients with ICAS and DM, SCAS and non-DM, SCAS and DM had increased risk of events [adjusted hazard ratio (HR): 1.709, 95% confidence interval (CI) 1.106-2.641, p = 0.016; HR: 1.911, 95% CI 1.460-2.501, p < 0.001; HR: 2.053, 95% CI 1.514-2.782, p < 0.001] compared to ones with NOCAS and non-DM. Besides, the Kaplan-Meier curves indicated the highest risk of MACEs in patients with SCAS and DM than others (p < 0.001).

Conclusions: Diabetic patients with ICAS had the worse outcome, which was comparable to patients with SCAS alone.
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http://dx.doi.org/10.1186/s12933-021-01403-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8542326PMC
October 2021

Metabolic-associated fatty liver disease and major adverse cardiac events in patients with chronic coronary syndrome: a matched case-control study.

Hepatol Int 2021 Dec 9;15(6):1337-1346. Epub 2021 Oct 9.

State Key Laboratory of Cardiovascular Disease, FuWai Hospital, National Center for Cardiovascular Diseases, National Clinical Research Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 BeiLiShi Road, XiCheng District, Beijing, 100037, People's Republic of China.

Background And Aims: A consensus of experts suggests that nonalcoholic fatty liver disease (NAFLD) does not appropriately reflect current knowledge and metabolic-associated fatty liver disease (MAFLD) is supposed to be a more suitable overarching concept. However, the association of MAFLD with cardiovascular outcomes in patients with coronary artery disease has not been examined yet. Thus, this study aimed to assess the impact of MAFLD on major adverse cardiac events (MACEs) in patients with chronic coronary syndrome (CCS).

Methods: This study included 3306 patients with CCS who were diagnosed with MAFLD. Controls without MAFLD were matched (1:1) to cases by age and gender. All participants were followed up for the occurrence of MACEs. Finally, the association between MAFLD and the risk of MACEs was assessed.

Results: During an average of 55.09 ± 19.92 months follow-up, 376 and 248 MACEs were observed in MAFLD and control groups, respectively. When compared with controls, Kaplan-Meier analysis showed that patients with MAFLD had significantly lower event-free survival rate and multivariate Cox regression analysis further revealed that MAFLD group had significantly increased MACEs risk (both p < 0.05). Stratification analysis suggested that patients with MAFLD overlapped with NAFLD or MAFLD-only had 1.33-fold and 2.32-fold higher risk of MACEs respectively compared with controls (both p < 0.05).

Conclusion: This study firstly showed that MAFLD was significantly associated with the risk of MACEs in patients with CCS. Moreover, this relationship remained unchanged irrespective of whether satisfying the NAFLD criteria, providing novel evidence for the good utility of MAFLD criteria in clinical practice.
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http://dx.doi.org/10.1007/s12072-021-10252-0DOI Listing
December 2021

Effect of vocal respiratory training on respiratory function and respiratory neural plasticity in patients with cervical spinal cord injury: a randomized controlled trial.

Neural Regen Res 2022 May;17(5):1065-1071

School of Rehabilitation Medicine, Capital Medical University; China Rehabilitation Science Institute; Beijing Key Laboratory of Neural Injury and Rehabilitation; Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China.

In previous studies, researchers have used singing to treat respiratory function in patients with spinal cord injury. However, few studies have examined the way in which vocal training affects respiratory neural plasticity in patients with spinal cord injury. Vocal respiratory training (VRT) is a type of vocal muscle-related treatment that is often a component of music therapy (MT) and focuses on strengthening respiratory muscles and improving lung function. In this randomized controlled study, we analyzed the therapeutic effects of VRT on respiratory dysfunction at 3 months after cervical spinal cord injury. Of an initial group of 37 patients, 26 completed the music therapy intervention, which comprised five 30-minute sessions per week for 12 weeks. The intervention group (n = 13) received VRT training delivered by professional certified music therapists. The control group (n = 13) received respiratory physical therapy delivered by professional physical therapists. Compared with the control group, we observed a substantial increase in respiratory function in the intervention group after the 12-week intervention. Further, the nerve fiber bundles in the respiratory center in the medulla exhibited a trend towards increased diversification, with an increased number, path length, thickness, and density of nerve fiber bundles. These findings provide strong evidence for the effect of music therapeutic VRT on neural plasticity. This study was approved by the Ethics Committee of China Rehabilitation Research Center (approval No. 2020-013-1) on April 1, 2020, and was registered with the Chinese Clinical Trial Registry (registration No. ChiCTR2000037871) on September 2, 2020.
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http://dx.doi.org/10.4103/1673-5374.324856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8552850PMC
May 2022

Heterodimers of metal nanoparticles: synthesis, properties, and biological applications.

Mikrochim Acta 2021 09 19;188(10):345. Epub 2021 Sep 19.

The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, People's Republic of China.

Heterodimers of metal nanoparticles consist of two metals, come in many sizes and adopt various shapes. They offer unique properties due to the presence of two metals and have the extraordinary flexibility needed to serve as a multipurpose platform for diverse applications in areas including photonics, sensing, and catalysis. Heterodimer nanoparticles contain different metals that contribute to extraordinary surface plasmon resonance (SPR), surface-enhanced Raman scattering (SERS), and catalytic properties. These properties make them versatile molecules that can be used in intracellular imaging, as antibacterial agents, as photocatalytic and biological macromolecules and for the detection of chemical substances. Moreover, heterodimer nanoparticles are composed of the two metals within larger molecules that provide more choices for modification and application. In this review, we briefly summarize the lesser-known aspects of heterodimers, including some of their properties, and present concrete examples of recent progress in synthesis and applications. This review provides a perspective on achievements and suggests a framework for future research with a focus on the synthesis and application of heterodimers. We also explore the possible applications of heterodimer nanoparticles based on their unique properties.
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http://dx.doi.org/10.1007/s00604-021-05002-wDOI Listing
September 2021

Upregulation of BIRC5 plays essential role in esophageal squamous cell carcinoma.

Math Biosci Eng 2021 08;18(5):6941-6960

Department of General Surgery, Second Affiliated Hospital of Guangxi Medical University, 166 DaxueXi Road, Nanning, Guangxi Zhuang Autonomous Region, 530021, P. R. China.

Background: Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers in the world, the detection and prognosis of which are still unsatisfactory. Thus, it is essential to explore the factors that may identify ESCC and evaluate the prognosis of ESCC patients.

Results: Both protein and mRNA expression levels of BIRC5 are upregulated in ESCC group rather than non-ESCC group (standardized mean difference > 0). BIRC5 mRNA expression is related to the age, tumor location, lymph node stage and clinical stage of ESCC patients (p < 0.05). BIRC5 expression makes it feasible to distinguish ESCC from non-ESCC (area under the curve > 0.9), and its high expression is related to poor prognosis of ESCC patients (restrictive survival time difference = -0.036, p < 0.05). BIRC5 may play an important role in ESCC by influencing the cell cycle pathway, and CDK1, MAD2L and CDC20 may be the hub genes of this pathway. The transcription factors-MAZ and TFPD1 -are likely to regulate the transcription of BIRC5, which may be one of the factors for the high expression of BIRC5 in ESCC.

Conclusions: The current study shows that upregulation of BIRC5 may have essential clinical value in ESCC, and contributes to the understanding of the pathogenesis of ESCC.
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http://dx.doi.org/10.3934/mbe.2021345DOI Listing
August 2021

Diagnostic value of thyroid micronodules with high b-value diffusion weighted imaging: Comparative study with high-resolution ultrasound.

Eur J Radiol 2021 Oct 14;143:109912. Epub 2021 Aug 14.

Department of Radiology, The Sixth Medical Center, Chinese PLA General Hospital, Beijing, China. Electronic address:

Purpose: This study aims to compare the diagnostic performance of two imaging methods for thyroid nodules ≤1.0 cm and reduce unnecessary overdiagnosis.

Methods: A retrospective study was conducted on 80 patients with pathologically confirmed solitary thyroid micronodules underwent both high-resolution ultrasound (HRUS) and High b-value (2000 s/mm) diffusion weighted imaging (DWI). Intra- and interobserver agreement (Intraclass correlation coefficient) was followed by Kruskal-Wallis test to detect whether the quantitative apparent diffusion coefficient (ADC) and thyroid nodule subgroups were related. Cohen's kappa analysis was applied to assess the interobserver consistency of DWI and HRUS characteristics. The receiver operating characteristic curves were adopted for evaluating the diagnostic performance of thyroid malignancy. The sensitivity, specificity, and accuracy of the two imaging methods were compared using the McNemar's test and Kappa test.

Results: A total of 80 patients were included, consisting of 43 malignant and 37 benign micronodules. The sensitivity, specificity and accuracy of DWI combined with rADC (ADCmin to ADCn ratio) for the diagnosis of thyroid micronodules were 83.7%, 89.2% and 86.3%, respectively. The area under the curve (AUC) was 0.91 (95% confidence interval [CI]: 0.84-0.97). The sensitivity, specificity and accuracy of HRUS diagnosis were 100%, 62.16% and 82.5%, respectively.

Conclusion: High b-value DWI is superior to HRUS for evaluating the diagnostic performance of solid thyroid micronodules. DWI and its ADC quantitative analysis could be added to the evaluation of thyroid micronodules to improve the specificity of diagnosis, reduce overdiagnosis and avoid unnecessary biopsies or surgeries.
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http://dx.doi.org/10.1016/j.ejrad.2021.109912DOI Listing
October 2021

Clinical significance and molecular mechanism of angiotensin-converting enzyme 2 in hepatocellular carcinoma tissues.

Bioengineered 2021 12;12(1):4054-4069

Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, P.R. China.

During the pandemic of the coronavirus disease 2019, there exist quite a few studies on angiotensin-converting enzyme 2 () and SARS-CoV-2 infection, while little is known about in hepatocellular carcinoma (HCC). The detailed mechanism among and HCC still remains unclear, which needs to be further investigated. In the current study with a total of 6,926 samples, expression was downregulated in HCC compared with non-HCC samples (standardized mean difference = -0.41). With the area under the curve of summary receiver operating characteristic = 0.82, expression showed a better ability to differentiate HCC from non-HCC. The mRNA expression of was related to the age, alpha-fetoprotein levels and cirrhosis of HCC patients, and it was identified as a protected factor for HCC patients via Kaplan-Meier survival, Cox regression analyses. The potential molecular mechanism of may be relevant to catabolic and cell division. In all, decreasing expression can be seen in HCC, and its protective role for HCC patients and underlying mechanisms were explored in the study.
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http://dx.doi.org/10.1080/21655979.2021.1952791DOI Listing
December 2021

Effectiveness of Melodic Intonation Therapy in Chinese Mandarin on Non-fluent Aphasia in Patients After Stroke: A Randomized Control Trial.

Front Neurosci 2021 23;15:648724. Epub 2021 Jul 23.

School of Rehabilitation Medicine, Capital Medical University, Beijing, China.

Melodic intonation therapy (MIT) positively impacts the speech function of patients suffering from aphasia and strokes. Fixed-pitch melodies and phrases formulated in MIT provide the key to the target language to open the language pathway. This randomized controlled trial compared the effects of music therapy-based MIT and speech therapy on patients with non-fluent aphasia. The former is more effective in the recovery of language function in patients with aphasia. Forty-two participants were enrolled in the study, and 40 patients were registered. The participants were randomly assigned to two groups: the intervention group ( = 20; 16 males, 4 females; 52.90 ± 9.08 years), which received MIT, and the control group ( = 20; 15 males, 5 females; 54.05 ± 10.81 years), which received speech therapy. The intervention group received MIT treatment for 30 min/day, five times a week for 8 weeks, and the control group received identical sessions of speech therapy for 30 min/day, five times a week for 8 weeks. Each participant of the group was assessed by a Boston Diagnostic Aphasia Examination (BDAE) at the baseline (t1, before the start of the experiment), and after 8 weeks (t2, the experiment was finished). The Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) were also measured on the time points. The best medical care of the two groups is the same. Two-way ANOVA analysis of variance was used only for data detection. In the spontaneous speech (information), the listening comprehension (right or wrong, word recognition, and sequential order) and repetitions of the intervention group were significantly higher than the control group in terms of the cumulative effect of time and the difference between groups after 8 weeks. The intervention group has a significant time effect in fluency, but the results after 8 weeks were not significantly different from those in the control group. In terms of naming, the intervention group was much better than the control group in spontaneous naming. Regarding object naming, reaction naming, and sentence completing, the intervention group showed a strong time accumulation effect. Still, the results after 8 weeks were not significantly different from those in the control group. These results indicate that, compared with speech therapy, MIT based on music therapy is a more effective musical activity and is effective and valuable for the recovery of speech function in patients with non-fluent aphasia. As a more professional non-traumatic treatment method, MIT conducted by qualified music therapists requires deeper cooperation between doctors and music therapists to improve rehabilitating patients with aphasia. The Ethics Committee of the China Rehabilitation Research Center approved this study (Approval No. 2020-013-1 on April 1, 2020) and was registered with the Chinese Clinical Trial Registry (Registration number: Clinical Trials ChiCTR2000037871) on September 3, 2020.
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http://dx.doi.org/10.3389/fnins.2021.648724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8344357PMC
July 2021

Tackling cardiometabolic risk in the Asia Pacific region.

Am J Prev Cardiol 2020 Dec 8;4:100096. Epub 2020 Nov 8.

Monash Cardiovascular Research Centre, Victorian Heart Institute, Monash University, Melbourne, Australia.

With the global spread of abdominal obesity, cardiovascular disease continues to spread to all countries of the world. Given the large population, the challenges presented by cardiometabolic risk in the Asia Pacific region are considerable. In addition to the clinical consequences of cardiovascular disease, in terms of its morbidity and mortality, the diversity of the Asia Pacific region brings heterogeneity in approaches to prevention, diagnosis and treatment of cardiometabolic risk. In this manuscript, we will review the current state of knowledge of cardiometabolic risk in Asia Pacific and highlight the needs moving forward to tackle this public health challenge.
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http://dx.doi.org/10.1016/j.ajpc.2020.100096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315619PMC
December 2020

Selective controlling transverse plasmon spectrum of pentagonal gold nanotube: from visible to near-infrared region.

Nanotechnology 2021 Aug 13;32(44). Epub 2021 Aug 13.

The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, People's Republic of China.

In this paper, the optical properties and local electric field distribution of transverse plasmon mode of a single pentagonal gold nanotube are studied for the first time by the discrete dipole approximation (DDA). We find that the transverse plasmon peaks can nonlinearly red shift from visible to infrared region via controlling the inner diameter. In addition, the transverse plasmon peak firstly blue shifts and then red shifts in the visible region with the increase of outer diameter. Further analysis shows that the spectra red shift with the increase of outer diameters when scattering is dominant. Local electric field analysis reveals that transverse plasmon resonance peaks of gold nanotube mainly come from dipole resonance. When the tube wall is thin enough, multi-polar plasmon resonance mode will be generated, and the number of peaks will be increased. The surface charges of inner and outer tube walls are changed by tuning the inner diameter and outer diameter parameters of pentagonal gold nanotube. The selective controlling transverse plasmon spectra of gold nanotube are realized, which is of great significance to the study of optical properties of gold nanotube and the application of molecular detection and biological imaging.
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http://dx.doi.org/10.1088/1361-6528/ac18a1DOI Listing
August 2021

Recent progress in the optical detection of pathogenic bacteria based on noble metal nanoparticles.

Mikrochim Acta 2021 07 16;188(8):258. Epub 2021 Jul 16.

The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, People's Republic of China.

Pathogenic bacteria have become a huge threat to social health and economy for their frighteningly infectious and lethal capacity. It is quite important to make a diagnosis in advance to prevent infection or allow a rapid treatment after infection. Noble metal nanoparticles, due to their unique physicochemical properties, especially optical properties, have drawn a great attention during the past decades and have been widely applied into all kinds of fields related to human health. By utilizing these noble metal nanoparticles, optical diagnosis platforms towards pathogenic bacteria have emerged continually, providing highly sensitive, selective, and particularly facile detection tools for clinic or point-of-care diagnosis. This review summarizes the recent development in this field. It begins with a brief introduction of pathogenic bacteria and noble metal nanoparticles. And then, optical detection methods are systematically discussed in three distinct aspects. In addition to these proof-of-concept methods, corresponding algorithms and point-of-care detection devices are also described. Finally, the review ends up with subjective views on present limitations and some appropriate advice for future research directions.
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http://dx.doi.org/10.1007/s00604-021-04885-zDOI Listing
July 2021

Association of triglyceride-rich lipoprotein-cholesterol with recurrent cardiovascular events in statin-treated patients according to different inflammatory status.

Atherosclerosis 2021 08 26;330:29-35. Epub 2021 Jun 26.

State Key Laboratory of Cardiovascular Disease, FuWai Hospital, National Center for Cardiovascular Diseases, National Clinical Research Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 BeiLiShi Road, XiCheng District, Beijing, China. Electronic address:

Background And Aims: The association of triglyceride-rich lipoprotein-cholesterol (TRL-C) with recurrent cardiovascular events (RCVEs) has not been studied. Moreover, whether inflammation can affect TRL-C-associated cardiovascular risk is unknown. This study sought to examine the association between TRL-C and RCVEs, and whether this relationship is modulated by systemic inflammation in statin-treated patients with coronary artery disease (CAD) and nearly normal triglyceride.

Methods: In this study, 6723 CAD patients were consecutively enrolled, following a first CVE with triglyceride <2.3 mmol/L. Baseline lipid profile and high-sensitivity C-reactive protein (hsCRP) levels were determined. All patients were searched for RCVEs. The risk of RCVEs was assessed across quartiles (Q) of baseline TRL-C and further stratified by the median of hsCRP.

Results: Over a mean follow-up of 58.91 ± 17.79 months, 538 RCVEs were recorded. After adjustment for potential confounders, Q4 of TRL-C was significantly associated with the risk of RCVEs, which remained unchanged after hsCRP stratification. When subjects were grouped according to both TRL-C and hsCRP levels, patients with Q4 of TRL-C and hsCRP had the highest increase of the risk of RCVEs compared with the reference group (TRL-C Q1-3 and hsCRP Q1-3; HR, 1.90; 95%CI: 1.27-2.87). Furthermore, adding TRL-C to the original predicting model led to a slight but significant improvement.

Conclusions: The present analysis firstly showed that elevated TRL-C was associated with an increased RCVEs risk in statin-treated patients with CAD independent of systemic inflammation, suggesting that it might be a useful marker for risk stratification and a treatment target in this patient population.
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http://dx.doi.org/10.1016/j.atherosclerosis.2021.06.907DOI Listing
August 2021

Spiky yolk-shell AuAg bimetallic nanorods with uniform interior gap for the SERS detection of thiram residues in fruit juice.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Dec 24;262:120108. Epub 2021 Jun 24.

The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China. Electronic address:

By using gold nanorods with silver coating as the sacrificial templates, we prepared spiky yolk-shell AuAg bimetallic nanorods with uniform interior gap via galvanic replacement reaction. The length and number of Au tips of the spiky yolk-shell AuAg nanorods can be tuned simultaneously by altering HAuCl volume. The influence of HAuCl volume and the sliver layer thickness on the SERS activity of spiky yolk-shell AuAg nanorods are studied. When the sliver layer is thin, the interior gap has not been shielded completely and the outer shell has obvious tips, thus the surface-enhanced Raman scattering (SERS) activity has the strongest enhancement with an enhancement factor (EF) of 4.9 × 10. The spiky yolk-shell AuAg nanorods with the strongest SERS activity are used as SERS substrates to detect thiram. The results demonstrate that the SERS intensity increases linearly with the logarithmic concentration of thiram in the range of 10 M to 10 M. The detection limit is as low as 97 nM, which is lower than the maximum pesticide residue limit (29 µM) in fruits stipulated by the US Environmental Protection Agency (EPA). Therefore, the spiky yolk-shell AuAg bimetallic nanorods have important practical application value in pesticide detection.
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http://dx.doi.org/10.1016/j.saa.2021.120108DOI Listing
December 2021

Expression and Biochemical Characterization of a Novel Marine Chitosanase from Suitable for Preparation of Chitobiose.

Mar Drugs 2021 May 24;19(6). Epub 2021 May 24.

National Key Laboratory of Biochemical Engineering, National Engineering Research Center for Biotechnology (Beijing), Key Laboratory of Biopharmaceutical Production & Formulation Engineering, PLA, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China.

It is known that bioactivities of chitooligosaccharide (COS) are closely related to the degree of polymerization (DP); therefore, it is essential to prepare COS with controllable DP, such as chitobiose showing high antioxidant and antihyperlipidemia activities. In this study, BLAST, sequence alignment and phylogenetic analysis of characterized glycoside hydrolase (GH) 46 -chitosanases revealed that a chitosanase Sn1-CSN from was different from others. Sn1-CSN was overexpressed in , purified and characterized in detail. It showed the highest activity at pH 6.0 and exhibited superior stability between pH 4.0 and pH 11.0. Sn1-CSN displayed the highest activity at 50 °C and was fairly stable at ≤45 °C. Its apparent kinetic parameters against chitosan (DDA: degree of deacetylation, >94%) were determined, with and values of 1.8 mg/mL and 88.3 s, respectively. Cu enhanced the activity of Sn1-CSN by 54.2%, whereas Fe inhibited activity by 15.1%. Hydrolysis products of chitosan (DDA > 94%) by Sn1-CSN were mainly composed of chitobiose (87.3%), whereas partially acetylated chitosan with DDA 69% was mainly converted into partially acetylated COS with DP 2-13. This -chitosanase has great potential to be used for the preparation of chitobiose and partially acetylated COS with different DPs.
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http://dx.doi.org/10.3390/md19060300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225178PMC
May 2021

Lipoprotein (a), hypertension, and cardiovascular outcomes: a prospective study of patients with stable coronary artery disease.

Hypertens Res 2021 Sep 25;44(9):1158-1167. Epub 2021 May 25.

State Key Laboratory of Cardiovascular Disease, FuWai Hospital, National Center for Cardiovascular Diseases, National Clinical Research Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Although emerging data suggest that circulating lipoprotein (a) [Lp (a)] could predict cardiovascular events (CVEs) in patients with cardiovascular disease, no study is currently available regarding the prognostic linkage of Lp (a) and hypertension in patients with coronary artery disease (CAD). This study sought to evaluate the association of Lp (a), hypertension and cardiovascular outcomes in patients with stable CAD. A total of 8668 patients with stable CAD were consecutively enrolled. Baseline Lp (a) concentrations were measured. All subjects were categorized according to Lp (a) levels of <10 (low), 10-30 (medium) and ≥30 mg/dL (high) and were further stratified by hypertension status. They were regularly followed-up for the occurrence of cardiovascular death, nonfatal myocardial infarction, and stroke. Over an average of 54.81 ± 18.60 months of follow-up, 584 (6.7%) CVEs occurred. Kaplan-Meier and multivariate Cox regression analyses showed that elevated Lp (a) levels had a significant association with CVEs in hypertensive patients, regardless of the control status of blood pressure, but not in normotensive subjects. Moreover, when analyzed by subgroups according to both Lp (a) category and hypertension status, the risk of CVEs was only significantly elevated in the high Lp (a) plus hypertension group compared with the reference group with low Lp (a) levels and normotension (hazard ratio: 1.80, 95% confidence interval: 1.11-2.91). Elevated Lp (a) was associated with an increased risk of CVEs in stable CAD patients with hypertension. Moreover, the coexistence of high Lp (a) concentrations and hypertension greatly worsened the clinical prognosis in patients with CAD, which may suggest a prognostic correlation between Lp (a) and hypertension.
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http://dx.doi.org/10.1038/s41440-021-00668-4DOI Listing
September 2021

Visit-to-visit variability of lipid and cardiovascular events in patients with familial hypercholesterolemia.

Ann Transl Med 2021 Apr;9(7):556

State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.

Background: Visit-to-visit variability in lipid has been suggested as a predictor of major adverse cardiovascular events (MACEs). However, no evidence exists on the prognostic value of lipid variability in patients with familial hypercholesterolemia (FH). This prospective cohort study aimed to investigate whether lipid variability affects future MACEs in patients with FH receiving standard lipid-lowering therapy.

Methods: A total of 254 patients with FH were consecutively enrolled and followed for MACEs. Variability in the triglyceride, total cholesterol, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C) and lipoprotein (a) [Lp(a)] were evaluated from 3 months after discharge using the standard deviation (SD), coefficient of variation (CV) and variability independent of the mean (VIM).

Results: During a mean follow-up of 49 months, 22 (8.7%) events occurred. Visit-to-visit variability in Lp(a) was significantly higher in the MACE group compared to the non-MACE group. In the multivariate Cox analysis, only Lp(a)-related parameters were independent predictors for MACEs. The hazard ratios and 95% confidence intervals of each 1-SD increase of SD, CV, and VIM of Lp(a) were 1.42 (1.12-1.80), 1.50 (1.11-2.02) and 1.60 (1.16-2.22), respectively. Kaplan-Meier analysis revealed that patients with higher Lp(a) variability presented lower event-free survival. The results were consistent in various subgroups.

Conclusions: Our study firstly suggested that Lp(a) variability was associated with MACEs in real-world patients with FH, which emphasized the importance of regular lipid monitoring in the patients with high risk.
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http://dx.doi.org/10.21037/atm-20-5324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105805PMC
April 2021

Homeobox-A13 acts as a functional prognostic and diagnostic biomarker via regulating P53 and Wnt signaling pathways in lung cancer.

Cancer Biomark 2021 ;31(3):239-254

Department of Oncology, Southwest Hospital, Army Medical University, Chongqing, China.

Background: The prognosis of lung cancer patients is poor without useful prognostic and diagnostic biomarker. To search for novel prognostic and diagnostic markers, we previously found homeobox-A13 (HOXA13) as a promising candidate in lung cancer.

Objective: To determine the precisely clinical feature, prognostic and diagnostic value, possible role and mechanism of HOXA13.

Methods: Gene-expression was explored by real-time quantitative-PCR, western-blot and tissue-microarray. The associations were analyzed by Chi-square test, Kaplan-Meier and Cox-regression. The roles and mechanisms were evaluated by MTS, EdU, transwell, xenograft tumor and luciferase-reporter assays.

Results: HOXA13 expression is increased in tumors, and correlated with age of patients. HOXA13 expression is associated with unfavorable overall survival and relapse-free survival of patients in four cohorts. Interestingly, HOXA13 has different prognostic significance in adenocarcinoma (ADC) and squamous-cell carcinoma (SCC), and is a sex- and smoke-related prognostic factor only in ADC. Importantly, HOXA13 can serve as a diagnostic biomarker for lung cancer, especially for SCC. HOXA13 can promote cancer-cell proliferation, migration and invasion in vitro, and facilitate tumorigenicity and tumor metastasis in vivo. HOXA13 acts the oncogenic roles on tumor growth and metastasis by regulating P53 and Wnt/β-catenin signaling activities in lung cancer.

Conclusions: HOXA13 is a new prognostic and diagnostic biomarker associated with P53 and Wnt/β-catenin signaling pathways.
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http://dx.doi.org/10.3233/CBM-200540DOI Listing
December 2021

Plasma proprotein convertase subtilisin/kexin type 9 concentration and recurrent cardiovascular events in patients with familial hypercholesterolemia.

Eur J Prev Cardiol 2021 04;28(3):272-279

State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital and National Center for Cardiovascular Diseases, China.

Aims: Familial hypercholesterolemia patients are characterized by early onset of coronary artery calcification and atherosclerosis, and high incidence of cardiovascular events. Plasma proprotein convertase subtilisin/kexin type 9 was reported to be a predictor for cardiovascular risk in the general population. However, its prognostic value for predicting recurrent cardiovascular events in familial hypercholesterolemia patients remains undetermined.

Methods: A total of 249 patients with molecularly and/or clinically (Dutch Lipid Clinic Network score > 6) defined familial hypercholesterolemia who had experienced a first cardiovascular event were consecutively included and plasma proprotein convertase subtilisin/kexin type 9 concentrations were measured by enzyme-linked immunosorbent assay. Coronary artery calcification was measured using Agatston method and coronary severity was assessed by Gensini score, respectively. All patients received standard lipid-lowering therapy and were followed-up for recurrent cardiovascular events. Univariate and multivariate regression and Cox analyses was used to calculate hazard ratios with 95% confidence interval.

Results: Circulating proprotein convertase subtilisin/kexin type 9 concentrations were positively associated with coronary artery calcification scores and Gensini score by both univariate and multivariate analyses. During a mean follow-up of 43 ± 19 months, 29 (11.51%) recurrent cardiovascular events occurred. Kaplan-Meier analysis showed that patients with the highest proprotein convertase subtilisin/kexin type 9 levels had the lowest event-free survival time. Multivariable Cox regression analysis revealed that proprotein convertase subtilisin/kexin type 9 was independently associated with recurrent cardiovascular events (hazard ratio: 1.45, 95% confidence interval: 1.11-1.88). The combination of proprotein convertase subtilisin/kexin type 9 to Cox prediction model led to an enhanced predictive value for recurrent cardiovascular events.

Conclusions: Increased level of proprotein convertase subtilisin/kexin type 9 was a significant risk factor of atherosclerosis and independently predicted future recurrent cardiovascular events in familial hypercholesterolemia patients receiving standard lipid-lowering treatment.
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http://dx.doi.org/10.1177/2047487319880985DOI Listing
April 2021

Prognostic value of NT-proBNP in patients with chronic coronary syndrome and normal left ventricular systolic function according to glucose status: a prospective cohort study.

Cardiovasc Diabetol 2021 04 22;20(1):84. Epub 2021 Apr 22.

State Key Laboratory of Cardiovascular Disease, FuWai Hospital, National Center for Cardiovascular Diseases, National Clinical Research Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 BeiLiShi Road, XiCheng District, 100037, Beijing, China.

Background: The prognostic value of N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with coronary artery disease (CAD) with different glucose status has not been established. This study sought to evaluate the significance of NT-proBNP in predicting major adverse cardiovascular events (MACEs) in patients with chronic coronary syndrome (CCS) and normal left-ventricular systolic function (LVSF) according to different glucose status, especially in those with abnormal glucose metabolism.

Methods: A total of 8062 patients with CCS and normal LVSF were consecutively enrolled in this prospective study. Baseline plasma NT-proBNP levels were measured. The follow-up data of all patients were collected. Kaplan-Meier and Cox regression analyses were used to assess the risk of MACEs according to NT-proBNP tertiles stratified by glucose status.

Results: Over an average follow-up of 59.13 ± 18.23 months, 569 patients (7.1 %) suffered from MACEs, including cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Kaplan-Meier analysis showed that high NT-proBNP levels had a significant association with MACEs in subjects with prediabetes mellitus (pre-DM) or DM, but not in patients with normoglycemia. Multivariate Cox regression analysis revealed that NT-proBNP remained an independent predictor of MACEs in patients with pre-DM [hazard ratio (HR): 2.56, 95% confidence interval (CI): 1.34-4.91] or DM (HR: 2.34, 95% CI: 1.32-4.16). Moreover, adding NT-proBNP to the original Cox model including traditional risk factors significantly increased the C-statistic by 0.035 in pre-DM and DM, respectively.

Conclusions: The present study indicated that NT-proBNP could well predict worse outcomes in dysglycemic patients with CCS and normal LVSF, suggesting that NT-proBNP may help with risk stratification in this population.
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http://dx.doi.org/10.1186/s12933-021-01271-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063320PMC
April 2021

Transjugular Intrahepatic Portosystemic Shunt Creation for the Prevention of Gastric Variceal Rebleeding in Patients with Hepatocellular Carcinoma: A Multicenter Retrospective Study.

J Vasc Interv Radiol 2021 07 20;32(7):963-969. Epub 2021 Apr 20.

Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address:

Purpose: To evaluate the effectiveness and safety of transjugular intrahepatic portosystemic shunt (TIPS) creation for the prevention of gastric variceal rebleeding in patients with hepatocellular carcinoma (HCC).

Materials And Methods: This multicenter retrospective study included 126 cirrhotic patients (mean age, 54.1 ± 10.2 years; 110 men) with HCC who underwent TIPS creation for the prevention of gastric variceal rebleeding. Of these, 110 (87.3%) patients had gastroesophageal varices and 16 (12.7%) patients had isolated gastric varices. Thirty-five (27.8%) patients had portal vein tumor thrombus.

Results: TIPS creation was technically successful in 124 (98.4%) patients. Rebleeding occurred in 26 (20.6%) patients during the follow-up period. The 6-week and 1-year actuarial probabilities of patients remaining free of rebleeding were 98.3% ± 1.2% and 81.2% ± 3.9%, respectively. Forty-nine (38.8%) patients died during the follow-up period. The 6-week and 1-year actuarial probabilities of survival were 98.4 ± 1.1% and 65.6 ± 4.4%, respectively. Two (1.6%) patients had major procedure-related complications, including acute liver failure (n = 1) and intra-abdominal bleeding (n = 1). Thirty-three (26.2%) patients had at least 1 episode of overt hepatic encephalopathy during the follow-up period. Shunt dysfunction occurred in 15 (11.9%) patients after a median follow-up time of 11.4 months (range, 1.4-41.3 months). Lung metastasis occurred in 3 (2.4%) patients, 3.9-32.9 months after TIPS creation.

Conclusions: TIPS creation may be effective and safe for the prevention of gastric variceal rebleeding in patients with HCC.
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http://dx.doi.org/10.1016/j.jvir.2021.04.005DOI Listing
July 2021
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