Publications by authors named "Yujie Zhou"

190 Publications

Synonymous point mutation of gtfB gene caused by therapeutic X-rays exposure reduced the biofilm formation and cariogenic abilities of Streptococcus mutans.

Cell Biosci 2021 May 17;11(1):91. Epub 2021 May 17.

State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, 610041, China.

Background: The shift of oral microbiota is a critical factor of radiation caries in head and neck cancer patients after the radiotherapy. However, the direct effects of irradiation on the genome and virulence of cariogenic bacteria are poorly described. Here we investigated the genomic mutations and virulence change of Streptococcus mutans (S. mutans), the major cariogenic bacteria, exposed to the therapeutic doses of X-rays.

Results: X-ray reduced the survival fraction of S. mutans and impacted its biofilm formation. We isolated a biofilm formation-deficient mutant #858 whose genome only possessed three synonymous mutations (c.2043 T > C, c.2100C > T, c.2109A > G) in gtfB gene. The "silent mutation" of c.2043 T > C in gtfB gene can cause the down-regulation of all of the gtfs genes' expression and decrease the GtfB enzyme secretion without the effect on the growth due to the codon bias. #858 and synonymous point mutation strain gtfB , similar to the gtfB gene null mutant Δ gtfB, can significantly decrease the extracellular polysaccharide production, biofilm formation and cariogenic capabilities both in vitro and in vivo compared with wild type.

Conclusion: The direct exposure of X-ray radiation can affect the genome and virulence of oral bacteria even at therapeutic doses. The synonymous mutations of genome are negligent factors for gene expression and related protein translation due to the codon usage frequency.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13578-021-00608-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130306PMC
May 2021

Intracoronary Imaging Versus Coronary Angiography to Guide Drug-Coated Balloon Intervention in Coronary Artery Disease: A Propensity-Matched Pilot Study Analysis.

Angiology 2021 May 7:33197211012518. Epub 2021 May 7.

Department of Cardiology, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing Anzhen Hospital, Capital Medical University, Beijing Key Laboratory of Precision Medicine of Coronary Atherosclerotic Disease, Clinical Center for Coronary Heart Disease, Beijing, People's Republic of China.

Limited data exist about the effect of intracoronary imaging (ICI)-guided drug-coated balloon (DCB) intervention on clinical end points. In all, 1157 patients with coronary artery disease treated with DCB between December 2014 and December 2017 at Beijing Anzhen Hospital were included in the final analysis in this cohort study. The primary end point was the incidence of target lesion failure (TLF), a composite of cardiac death, target vessel myocardial infarction (MI), and target lesion revascularization, and the key secondary end point was the incidence of cardiac death or target vessel MI. The median follow-up for clinical events was 32.0 months (IQR 25.0-40.0). Intracoronary imaging was used in 90 (7.8%) patients. There was no statistically significant difference in TLF (12.2% vs 12.5%, = .80) between ICI-guided and angiography-guided group. Cardiac death or target vessel MI rates (1.1% vs 3.7%, = .17) were numerically lower for the ICI-guided cohort. In the propensity score-based analysis, TLF (10.5% vs 16.2%, = .19) and cardiac death or target vessel MI rates (1.2% vs 2.3%, = .51) tended to be lower for the ICI-guided cohort. In this observational study, TLF rate tended to decrease in the ICI-guided DCB treatment group compared with angiography-guided procedures. Larger studies are needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/00033197211012518DOI Listing
May 2021

The cross-kingdom interaction between Helicobacter pylori and Candida albicans.

PLoS Pathog 2021 May 6;17(5):e1009515. Epub 2021 May 6.

State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & West China School of Stomatology, Sichuan University, Chengdu, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.ppat.1009515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101746PMC
May 2021

Feasibility and Safety of the Novel Vivolight Frequency Domain Optical Coherence Tomography System: A Multicenter Study.

J Invasive Cardiol 2021 Jun 8;33(6):E412-E415. Epub 2021 Apr 8.

Department of Cardiology, The General Hospital of the People's Liberation Army, 28 Fuxing Road, Beijing (Wukesong), China.

Objective: The study sought to assess the effectiveness and safety of the novel P60 Vivolight frequency-domain optical coherence tomography (OCT) system (Shenzhen Vivolight Medical Device & Technology).

Methods: A total of 90 patients were enrolled from 3 institutions. The pullbacks were performed with both the P60 Vivolight OCT system and the Ilumien Optis OCT system (Abbott Vascular). The primary endpoint was the clear stent length (CSL). Device safety was assessed by the record of serious procedure-related or postprocedure adverse events. The secondary endpoints were the average lumen area of stent, clear image length (CIL), system stability, and imaging catheter operability.

Results: The mean relative errors of CSL were 3.30% (95% confidence interval [CI], -0.71 to 7.31) in the full analysis set (FAS) and 0.83% (95% CI, -1.79 to 3.45) in the per-protocol set (PPS). The mean relative errors of the average lumen area of stent were 2.20% (95% CI, 0.70 to 3.80) in the FAS and 1.55% (95% CI, 0.30 to 2.80) in the PPS. No difference was observed in the percentage of obtaining >24 mm of CIL (93.18% in the P60 Vivolight group vs 95.45% in the Ilumien Optis group; P=.48). There were no serious procedure-related or postprocedure adverse events.

Conclusions: The feasibility and safety of the novel Vivolight OCT system is equivalent to that of the Ilumien Optis OCT system.
View Article and Find Full Text PDF

Download full-text PDF

Source
June 2021

Cadmium pollution of soil-rice ecosystems in rice cultivation dominated regions in China: A review.

Environ Pollut 2021 Jul 17;280:116965. Epub 2021 Mar 17.

School of Geography and Ocean Science, Nanjing University, Nanjing, 210023, China; Key Laboratory of Coastal Zone Exploitation and Protection, Ministry of Natural Resources, Nanjing, 210024, China.

Cd accumulation in paddy soils and its subsequent transfer to the food chain are widespread environmental issues, which has been extensively investigated in China. However, most studies focused on regional scales and these results may not be applicable to present the Cd contamination status in soil-rice ecosystems at a national scale. Therefore, based on collected data from China's rice cultivation dominated regions, this study provides the Cd pollution level of paddy soils and rice grains in China. Results indicates that the Yangtze River basin, especially Hunan, required more attention due to the elevated Cd concentrations in soil-rice ecosystems. Moreover, this review summarizes the significant natural and anthropogenic sources, transport and accumulation mechanism as well as the influencing factors of Cd in soil-rice ecosystems. The wide occurrence of Cd contamination in paddy soils derived primarily from mining activities, intensive application of phosphates fertilizers and e-waste. Physicochemical characteristics of soil, soil microorganisms, temperature as well as the physiological features of rice plants all contribute to Cd accumulation in rice grains, which can be controlled to mitigate Cd accumulation in rice grains. This review will provide a scientific reference for Cd pollution control and management with respect to paddy field ecosystems in China and other countries.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envpol.2021.116965DOI Listing
July 2021

A Synergistic Effect of Lp(a) and GRACE Score on Cardiovascular Risk in Acute Coronary Syndrome Patients Undergoing Percutaneous Coronary Intervention: A Cohort Study From China.

Front Cardiovasc Med 2021 19;8:637366. Epub 2021 Feb 19.

Department of Cardiology, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.

Lipoprotein(a) [Lp(a)] has been thought as an independent risk factor for atherosclerotic cardiovascular disease (ASCVD). The Global Registry of Acute Coronary Events (GRACE) score is used to predict the risk of death or death/non-fatal myocardial infarction in patients with acute coronary syndromes (ACS). It suggests that there may be a synergism between Lp(a) and the GRACE risk score on predicting cardiovascular events. Accordingly, this study aimed to test the hypothesis that Lp(a)-related cardiovascular risk could be significantly modulated by the GRACE risk score in patients with ACS undergoing percutaneous coronary intervention (PCI). Patients hospitalized with ACS undergoing PCI were enrolled and followed up for 18 months. The primary outcome was the composite of death, non-fatal myocardial infarction, non-fatal stroke, and unplanned repeat revascularization. A Cox proportional hazard regression model was used to determine the relationship between Lp(a) and cardiovascular events. A total of 6,309 patients were included (age: 60.1 ± 10.06 years, male: 75.2%, BMI: 26.2 ± 10.57 kg/m). A total of 310 (4.9%) cardiovascular events occurred. When the overall population was stratified by a GRACE score of 91 or less vs. more than 91 and by tertiles of Lp(a), higher Lp(a) was significantly associated with cardiovascular events only when the GRACE score was <91(tertile 2 vs. tertile 1: HR 1.31, 95% CI: 0.86-1.98, = 0.205; tertile 3 vs. tertile 1: HR 1.94, 95% CI: 1.32-2.84, = 0.001; = 0.002). However, no such significant correlation between cardiovascular events and Lp(a) emerged in the case of a GRACE score 91 or less, and there was a significant interaction for cardiovascular events between Lp(a) tertiles and dichotomized GRACE scores ( < 0.001). In ACS patients undergoing PCI, there was a synergistic effect between the GRACE risk score and on-statins Lp(a) on predicting cardiovascular events. This finding could help us more accurately identify patients who would benefit most from Lp(a)-lowering treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcvm.2021.637366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933013PMC
February 2021

Tumor immune microenvironment-based classifications of bladder cancer for enhancing the response rate of immunotherapy.

Mol Ther Oncolytics 2021 Mar 4;20:410-421. Epub 2021 Feb 4.

Department of Urology, The First Affiliated Hospital of Anhui Medical University, Institute of Urology, Anhui Medical University, Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei 230022, P.R. China.

Immunotherapy is a potential way to save the lives of patients with bladder cancer, but it only benefits approximately 20% of them. A total of 4,028 bladder cancer patients were collected for this study. Unsupervised non-negative matrix factorization and the nearest template prediction algorithms were employed for the classification. We identified the immune and non-immune classes from The Cancer Genome Atlas Bladder Urothelial Carcinoma (TCGA-BLCA) training cohort. The 150 most differentially expressed genes between these two classes were extracted, and the classification reappeared in 20 validation cohorts. For the activated and exhausted subgroups, a stromal activation signature was assessed by the NTP algorithm. Patients in the immune class showed highly enriched signatures of immunocytes, while the exhausted subgroup also exhibited activated transforming growth factor (TGF)-β1, and cancer-associated extracellular matrix signatures. Patients in the immune-activated subgroup showed a lower genetic alteration and better overall survival. Anti-PD-1/PD-L1 immunotherapy was more beneficial for the immune-activated subgroup, while immune checkpoint blockade therapy plus a TGF-β inhibitor or an EP300 inhibitor might achieve greater efficacy for patients in the immune-exhausted subgroup. Novel immune molecular classifier was identified for the innovative immunotherapy of patients with bladder cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.omto.2021.02.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900642PMC
March 2021

Right Ventricular Damage in COVID-19: Association Between Myocardial Injury and COVID-19.

Front Cardiovasc Med 2021 16;8:606318. Epub 2021 Feb 16.

Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, is a global pandemic. It has resulted in considerable morbidity and mortality around the world. The respiratory system is the main system invaded by the virus involved in COVID-19. In addition to typical respiratory manifestations, a certain proportion of severe COVID-19 cases present with evidence of myocardial injury, which is associated with excessive mortality. With availability of an increasing amount of imaging data, right ventricular (RV) damage is prevalent in patients with COVID-19 and myocardial injury, while left ventricular damage is relatively rare and lacks specificity. The mechanisms of RV damage may be due to increased RV afterload and decreased RV contractility caused by various factors, such as acute respiratory distress syndrome, pulmonary thrombosis, direct viral injury, hypoxia, inflammatory response and autoimmune injury. RV dysfunction usually indicates a poor clinical outcome in patients with COVID-19. Timely and effective treatment is of vital importance to save patients' lives as well as improve prognosis. By use of echocardiography or cardiovascular magnetic resonance, doctors can find RV dilatation and dysfunction early. By illustrating the phenomenon of RV damage and its potential pathophysiological mechanisms, we will guide doctors to give timely medical treatments (e.g., anticoagulants, diuretics, cardiotonic), and device-assisted therapy (e.g., mechanical ventilation, extracorporeal membrane oxygenation) when necessary for these patients. In the paper, we examined the latest relevant studies to investigate the imaging features, potential mechanisms, and treatments of myocardial damage caused by COVID-19. RV damage may be an association between myocardial damage and lung injury in COVID-19. Early assessment of RV geometry and function will be helpful in aetiological determination and adjustment of treatment options.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcvm.2021.606318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920943PMC
February 2021

Elevated Glycated Albumin in Serum Is Associated with Adverse Cardiac Outcomes in Patients with Acute Coronary Syndrome Who Underwent Revascularization Therapy.

J Atheroscler Thromb 2021 Feb 27. Epub 2021 Feb 27.

Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing Key Laboratory of Precision Medicine of Coronary Atherosclerotic Disease, Clinical center for coronary heart disease, Capital Medical University.

Aims: The associations between increased glycated albumin (GA) in the serum and diabetic complications and mortality have been revealed in the general population. However, less is known regarding the prognostic value of GA in patients diagnosed with acute coronary syndrome (ACS).

Methods: In this study, all patients admitted for ACS who underwent a successful percutaneous coronary intervention (PCI) at our center from January 2018 to February 2019 were retrospectively examined. Clinical characteristics, laboratory results (e.g., serum GA levels), and procedural details were collected. The primary outcome included a composite of major adverse cardio-cerebral events (MACCE), such as death, myocardial infarction, stroke, and unplanned revascularization. The association between serum GA levels and clinical outcomes was tested in three multivariable models using Cox proportional hazard analysis. Subgroup analysis was performed in patients who were diagnosed with diabetes versus patients without diabetes.

Results: A total of 1,806 ACS patients (mean age of 59.4 years; 77.8% were men; 44.9% were diagnosed with diabetes) were enrolled in this study, where the majority exhibited unstable angina (81.6%) and showed preserved left ventricular systolic function. Patients in the high GA level group were commonly female and were more likely to have metabolic disorders and to exhibit severe CAD (all p<0.05). MACCE occurred in 126 patients (7.0%) during a mean follow-up time of 17.2 months. The cumulative risk of MACCE at the 18-month follow-up visit significantly increased in a stepwise fashion along with increased GA levels (log-rank p=0.018) in the serum. The association between serum GA levels and MACCE was further determined after adjusting traditional risk factors and hemoglobin A1c (HbA1c) (GA, per 1% increase: hazard ratio [HR] 1.09, 95% confidence interval [CI] 1.06-1.13; GA, higher vs. lower tertial: HR 1.92, 95% CI 1.01-3.67). In a subgroup analysis, the prognostic role of serum GA only existed in diabetic patients, even when adjusting for traditional risk factors and HbA1c levels.

Conclusions: Elevated GA levels in the serum were associated with poor intermediate-term outcomes in low-risk ACS patients who underwent PCI, especially in patients with preexisting diabetes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5551/jat.61358DOI Listing
February 2021

Formation of nitro(so) and chlorinated products and toxicity alteration during the UV/monochloramine treatment of phenol.

Water Res 2021 Apr 8;194:116914. Epub 2021 Feb 8.

Guangdong Provincial Key Laboratory of Environmental Pollution Control and Remediation Technology, School of Environmental Science and Engineering, Sun Yat-Sen University, Guangzhou, 510275, PR China. Electronic address:

The UV/monochloramine (UV/NHCl) process is an emerging advanced oxidation process (AOP) to remove organic contaminants in water treatment with radicals including hydroxyl radicals (HO), reactive chlorine species (RCS) and reactive nitrogen species (RNS). This study investigated the formation of nitro(so) and chlorinated products and toxicity alteration during the UV/NHCl treatment of phenol. RNS and/or RCS induced the formation of nitro(so), chlorinated and polymeric compounds during phenol transformation by UV/NHCl. These compounds dramatically increased the cytotoxicity to Chinese hamster ovary cells after 20 min UV/NHCl treatment, which was 10 times higher than that after 24 h chloramination. The increase of cytotoxicity in UV/NHCl was primarily attributable to 4-nitrosophenol, and the cytotoxicity followed the order of 4-nitrosophenol > 4-nitrophenol > 2,4,6-trichlorophenol > 2,4-dichlorophenol > phenol. 4-Nitrosophenol was significantly generated by the combination of NO and phenoxy radical, where the maximum conversion rates of phenol to 4-nitrosophenol increased from 4.9% to 62.4% when pH increased from 5 to 10. The highest conversion rate was at pH 10 because the NO concentration increased with increasing pH from 5 to 10 in UV/NHCl, as verified by the electron paramagnetic resonance (EPR) analysis. Nitrophenols were also detected at much lower concentrations than 4-nitrosophenol, which were mainly formed by the oxidation of 4-nitrosophenol and the combination of NO with phenoxy radicals. RCS was responsible for the formation of chlorinated products mainly through Cl addition and the reactions of Cl/Cl with phenoxy radicals. Also, RCS and RNS significantly enhanced the formation of carbonaceous (i.e., chloroform and chloral hydrate) and nitrogenous disinfection byproducts (i.e., chloropicrin and dichloroacetonitrile) in UV/NHCl. This study indicates that the UV/NHCl treatment significantly increased toxicity and validates the roles of RNS and RCS in producing toxic nitro(so) and chlorinated products.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.watres.2021.116914DOI Listing
April 2021

Candida albicans CHK1 gene from two-component system is essential for its pathogenicity in oral candidiasis.

Appl Microbiol Biotechnol 2021 Mar 26;105(6):2485-2496. Epub 2021 Feb 26.

State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, 610041, Sichuan, China.

The roles of Candida albicans CHK1, a key gene from two-component system, in oral mucosal infection are not clear. This study evaluated the key roles of CHK1 gene in vitro and in vivo. The expression of CHK1 and its regulated virulence factors were tested during the oral epithelial cell infection. The production of lactate dehydrogenase, ROS, and IL-1α combined with the confocal and scanning electron microscope observation was employed to identify the capability of CHK1 in damaging the epithelial cells. Both immunocompetent and immunodeficient mice oropharyngeal infection models were involved to confirm the roles of CHK1 gene in vivo. The expression of CHK1 gene was significantly increased during the oral epithelial cell infection. The chk1Δ/Δ mutant failed to damage the epithelial cells or induce IL-α and ROS production. Interestingly, chk1Δ/Δ can also form the similar hyphae with WT and complementary strains. Accordingly, chk1Δ/Δ did not affect the adhesion and invasion rates of C. albicans to oral epithelial cells. However, chk1Δ/Δ significantly decreased the expression levels of the virulence factors, including ALS2, SAP6, and YWP1. The chk1Δ/Δ also failed to cause oral candidiasis in both immunocompetent and immunodeficient mice indicating that CHK1 gene from the two-component system is essential for the pathogenicity of C. albicans. KEY POINTS: • CHK1gene is essential for C. albicans in oral candidiasis • C. albicans without CHK1 gene can form "non-pathogenic" hyphae. • CHK1 gene regulates the virulence of C. albicans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00253-021-11187-0DOI Listing
March 2021

Relationship between coronary hyper-intensive plaques identified by cardiovascular magnetic resonance and clinical severity of acute coronary syndrome.

J Cardiovasc Magn Reson 2021 02 25;23(1):12. Epub 2021 Feb 25.

Cedars-Sinai Medical Center, Biomedical Imaging Research Institute, Los Angeles, CA, USA.

Background: Coronary hyper-intense plaque (CHIP) detected on T1-weighted cardiovascular magnetic resonance (CMR) has been shown to associate with vulnerable plaque features and worse outcomes in low- and intermediate-risk populations. However, the prevalence of CHIP and its clinical significance in the higher-risk acute coronary syndrome (ACS) population have not been systematically studied. This study aims to assess the relationship between CHIP and ACS clinical severity using intracoronary optical coherence tomography (OCT) as the reference.

Methods: A total of 62 patients with known or suspected coronary artery disease were prospectively enrolled including a clinically diagnosed ACS group (n = 50) and a control group with stable angina pectoris (n = 12). The ACS group consisted of consecutive patients including unstable angina pectoris (n = 27), non-ST-segment-elevation myocardial infarction (non-STEMI) (n = 8), and ST-segment-elevation myocardial infarction (STEMI) (n = 15), respectively. All patients underwent non-contrast coronary CMR to determine the plaque-to-myocardium signal intensity ratio (PMR).

Results: Among the four groups of patients, a progressive increase in the prevalence of CHIPs (stable angina, 8%; unstable angina, 26%; non-STEMI, 38%; STEMI, 67%; p = 0.009), and PMR values (stable angina, 1.1; unstable angina, 1.2; non-STEMI, 1.3; STEMI, 1.6; median values, P = 0.004) were observed. Thrombus (7/8, 88% vs. 4/22, 18%, p = 0.001) and plaque rupture (5/8, 63% vs. 2/22, 9%, p = 0.007) were significantly more prevalent in CHIPs than in plaques without hyper-intensity. Elevated PMR was associated with high-risk plaque features including plaque rupture, thrombus, and intimal vasculature. A positive correlation was observed between PMR and the number of high-risk plaque features identified by OCT (r = 0.44, p = 0.015).

Conclusions: The prevalence of CHIPs and PMR are positively associated with the disease severity and high-risk plaque morphology in ACS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12968-021-00706-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905639PMC
February 2021

Correction: Psychological Impact of the COVID-19 Pandemic on Chinese Health Care Workers: Cross-Sectional Survey Study.

JMIR Ment Health 2021 Feb 2;8(2):e27596. Epub 2021 Feb 2.

General Medical Department, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China.

[This corrects the article DOI: 10.2196/23125.].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2196/27596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886610PMC
February 2021

Tumour microenvironment-based molecular profiling reveals ideal candidates for high-grade serous ovarian cancer immunotherapy.

Cell Prolif 2021 Mar 31;54(3):e12979. Epub 2021 Jan 31.

State Key laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.

Objective: Due to limited immunological profiles of high-grade serous ovarian cancer (HGSOC), we aimed to characterize its molecular features to determine whether a specific subset that can respond to immunotherapy exists.

Materials And Methods: A training cohort of 418 HGSOC samples from TCGA was analysed by consensus non-negative matrix factorization. We correlated the expression patterns with the presence of immune cell infiltrates, immune regulatory molecules and other genomic or epigenetic features. Two independent cohorts containing 482 HGSOCs and in vitro experiments were used for validation.

Results: We identified immune and non-immune groups where the former was enriched in signatures that reflect immune cells, infiltration and PD-1 signalling (all, P < 0.001), and presented with a lower chromosomal aberrations but increased neoantigens, tumour mutation burden, and microsatellite instability (all, P < 0.05); this group was further refined into two microenvironment-based subtypes characterized by either immunoactivation or carcinoma-associated fibroblasts (CAFs) and distinct prognosis. CAFs-immune subtype was enriched for factors that mediate immunosuppression and promote tumour progression, including highly expressed stromal signature, TGF-β signalling, epithelial-mesenchymal transition and tumour-associated M2-polarized macrophages (all, P < 0.001). Robustness of these immune-specific subtypes was verified in validation cohorts, and in vitro experiments indicated that activated-immune subtype may benefit from anti-PD1 antibody therapy (P < 0.05).

Conclusion: Our findings revealed two immune subtypes with different responses to immunotherapy and indicated that some HGSOCs may be susceptible to immunotherapies or combination therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cpr.12979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941229PMC
March 2021

Associations between hyperhomocysteinemia and the presence and severity of acute coronary syndrome in young adults ≤ 35 years of age.

BMC Cardiovasc Disord 2021 01 23;21(1):47. Epub 2021 Jan 23.

Department of Cardiology, VIP Ward, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing Key Laboratory of Precision Medicine of Coronary Atherosclerotic Disease, Clinical Center for Coronary Heart Disease, Capital Medical University, Beijing, 100029, China.

Background: The prevalence of acute coronary syndrome (ACS) continues to increase among young Chinese adults. Homocysteine (HCY) has been suggested as a promoter of atherosclerosis leading to coronary artery disease (CAD). Yet, it remains uncertain whether HCY is associated with the ACS and the severity of coronary artery stenosis in young adults.

Methods: Young patients (18-35 years of age) diagnosed with ACS who underwent coronary angiography (CAG) at Anzhen Hospital between January 2013 and June 2019 were assigned to the ACS group. As confirmed by CAG during the same period, an equivalent age-matched population without CAD was assigned to the non-CAD group. A serum HCY level > 15 µmol/L was defined as hyperhomocysteinemia (HHCY). The Gensini score assessed the severity of coronary artery stenosis.

Results: A total of 1103 participants, including 828 ACS patients and 275 non-CAD subjects, were enrolled in this study. Young ACS patients had higher level of serum HCY and greater prevalence of HHCY compared with non-CAD subjects [for HCY, 16.55 (11.93-29.68) vs 12.50 (9.71-17.42), P < 0.001; for HHCY prevalence, 62.08% vs 26.18%, P < 0.001]. Multivariate logistic regression analysis with the stepwise method indicated that HHCY was an independent predictor associated with the presence of ACS, after adjusting for traditional confounders (OR, 4.561; 95% CI, 3.288-6.327; P < 0.001). Moreover, young ACS patients with HHCY had increased prevalence of ST-segment elevation myocardial infarction (STEMI) (P = 0.041), multi-vessel disease (P = 0.036), and decreased value of left ventricular ejection fraction (LVEF) (P = 0.01). Also, the HCY level was significantly correlated with Gensini Score in ACS patients (r = 0.142, P < 0.001).

Conclusion: HHCY is significantly associated with the presence of ACS and the severity of coronary artery stenosis in young adults ≤ 35 years of age.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12872-021-01869-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825206PMC
January 2021

Can Immunotherapy Combined With Antiangiogenic Therapy Be a Breakthrough for Driver-Negative Non-small-Cell Lung Cancer Patients With Performance Status of 3-4 in the First-Line Setting?

Am J Ther 2020 Dec 28;Publish Ahead of Print. Epub 2020 Dec 28.

Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital,Nanjing, China Department of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MJT.0000000000001305DOI Listing
December 2020

Perivascular Adipose Tissue as an Indication, Contributor to, and Therapeutic Target for Atherosclerosis.

Front Physiol 2020 18;11:615503. Epub 2020 Dec 18.

Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing, China.

Perivascular adipose tissue (PVAT) has been identified to have significant endocrine and paracrine functions, such as releasing bioactive adipokines, cytokines, and chemokines, rather than a non-physiological structural tissue. Considering the contiguity with the vascular wall, PVAT could play a crucial role in the pathogenic microenvironment of atherosclerosis. Growing clinical evidence has shown an association between PVAT and atherosclerosis. Moreover, based on computed tomography, the fat attenuation index of PVAT was verified as an indication of vulnerable atherosclerotic plaques. Under pathological conditions, such as obesity and diabetes, PVAT shows a proatherogenic phenotype by increasing the release of factors that induce endothelial dysfunction and inflammatory cell infiltration, thus contributing to atherosclerosis. Growing animal and human studies have investigated the mechanism of the above process, which has yet to be fully elucidated. Furthermore, traditional treatments for atherosclerosis have been proven to act on PVAT, and we found several studies focused on novel drugs that target PVAT for the prevention of atherosclerosis. Emerging as an indication, contributor to, and therapeutic target for atherosclerosis, PVAT warrants further investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphys.2020.615503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775482PMC
December 2020

Application of acellular dermal matrix to reconstruct the defects after hypopharyngeal carcinoma resection.

Am J Otolaryngol 2021 Mar-Apr;42(2):102847. Epub 2020 Dec 17.

Department of Otorhinolaryngology, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang, China. Electronic address:

Purpose: Reconstruction of the defects and recovery of the laryngopharyngeal function after resection of hypopharyngeal carcinoma are crucial for patients to promote the rate of survival and the quality of life. We launched this study to explore the advantages and limitations of acellular dermal matrix applied in the reconstruction of the defects after hypopharyngeal carcinoma surgery.

Materials And Methods: Collected the clinical and pathological data of patients with hypopharyngeal carcinoma, divided them into 2 groups according to the repair materials used (pectoralis major myocutaneous flap or acellular dermal matrix). The clinical data and postoperative complications were analyzed and compared.

Results: No matter whether the pectoralis major myocutaneous flap or acellular dermal matrix was used to repair hypopharyngeal cancer resection defects, the postoperative complications, especially the pharyngeal fistula rate, were not significantly different. The postoperative drainage volume of patients with acellular dermal matrix was less than that of patients with pectoralis major myocutaneous flap.

Conclusions: Acellular dermal matrix is a safe and effective biomedical material for hypopharyngeal cancer operation defects repair and pharyngeal function reconstruction, which can simplify the operation process, reduce the postoperative drainage volume, and decrease the risk of wound infection or pharyngeal fistula.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.amjoto.2020.102847DOI Listing
December 2020

Psychological Impact of the COVID-19 Pandemic on Chinese Health Care Workers: Cross-Sectional Survey Study.

JMIR Ment Health 2021 01 20;8(1):e23125. Epub 2021 Jan 20.

General Medical Department, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China.

Background: The outbreak of COVID-19 has dominated headlines worldwide. The number of infections has continued to rise and had reached 30,000 worldwide at the time this paper was written. Because of the high risk of nosocomial transmission, medical health care workers may be experiencing substantial psychological stress. This descriptive study aimed to identify psychosocial effects on hospital staff associated with working in a hospital environment during the COVID-19 outbreak.

Objective: Our survey participants included 57 frontline clinicians working at Wuhan First Hospital and 157 medical students working at Jiangsu Provincial People's Hospital during the COVID-19 outbreak. The questionnaire we adopted included questions regarding the participants' personal well-being, sociodemographic characteristics, and psychological status.

Methods: 57 frontline clinicians working in Wuhan First Hospital and 157 medical training students working in Jiangsu Provincial Peoples Hospital during this outbreak participated in our survey. The questionnaire we adopted included questions regarding the participants' personal well-being, sociodemographic characteristics and the psychological status.

Results: The COVID-19 outbreak had psychological impacts both on formal workers and medical students. The psychological effects included sleep disorders, anxiety, and depression. There was no significant difference between the group of formal workers and medical students (P=.85), and more than 50% (30/54, 56%, vs. 83/157, 52.9%) of the respondents reported pandemic-related mental disorders.

Conclusions: Our study indicates that the high risk of SARS-CoV-2 exposure caused substantial psychological stress among health care workers. This finding emphasizes the need to promote psychological crisis intervention for medical personnel during this epidemic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2196/23125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819543PMC
January 2021

Immune response drives outcomes in prostate cancer: implications for immunotherapy.

Mol Oncol 2021 May 29;15(5):1358-1375. Epub 2020 Dec 29.

Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

The heterogeneity of the immune microenvironment leads to different responses in immune checkpoint blockade therapy. We aimed to propose a robust molecular classification system to investigate the relevance of the immune microenvironment subtype and prognosis of prostate cancer patients, as well as the therapeutic response to immune checkpoint blockade therapy. A total of 1,557 prostate cancer patients were enrolled, including 69 real-world samples from our institute (titled the AHMU-PC cohort). The non-negative matrix factorization algorithm was employed to virtually microdissect patients. The immune enrichment was characterized by a high enrichment of T cell-, B cell-, NK cell-, and macrophage-associated signatures, by which patients were subclassified into nonimmune and immune classes. Subsequently, the immune class was dichotomized into immune-activated and immune-suppressed subtypes based on the stromal signature, represented by the activation of WNT/TGF-β, TGF-β1, and C-ECM signatures. Approximately 14.9% to 24.3% of patients belonged to the immune-activated subtype, which was associated with favorable recurrence-free survival outcomes. In addition, patients in the immune-activated subtype were predicted to benefit more from anti-PD-1/PD-L1 therapy. In conclusion, our study identifies a novel immune molecular classifier that is closely related to clinical prognosis and provides novel insights into immunotherapeutic strategies for prostate cancer patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/1878-0261.12887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096785PMC
May 2021

The relationship between residual cholesterol risk and plaque characteristics in patients with acute coronary syndrome: Insights from an optical coherence tomography study.

Atherosclerosis 2021 01 30;317:10-15. Epub 2020 Nov 30.

Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China. Electronic address:

Background And Aims: The impact of residual cholesterol risk (RCR) on plaque characteristics is not fully understood. The study aims to explore the relationship between RCR and plaque features in patients presenting with acute coronary syndrome (ACS).

Methods: All ACS patients undergoing pre-intervention optical coherence tomography (OCT) with high-sensitivity C-reactive protein (hs-CRP) <2 mg/L on admission were retrospectively enrolled from January to December 2017, at Beijing Anzhen Hospital, Capital Medical University. RCR was defined as low density lipoprotein cholesterol (LDL-C) ≥1.8 mmol/L. Patients were divided into the RCR and non-RCR groups according to baseline LDL-C.

Results: A total of 90 patients (94 vessels) were included, with 50 in the RCR group and 40 in the non-RCR group, respectively. Compared with the non-RCR group, patients in the RCR group were younger (54.0 ± 11.04 vs. 58.4 ± 9.59, p = 0.049) and had a higher incidence of multivessel disease (6.0% vs. 2.5%, p = 0.028). With regard to plaque characteristics, fibrous plaque (0.0% vs 12.5%, p = 0.003) was less and fibroatheroma (79.6% vs. 50.0%, p = 0.028) was more frequently seen in the RCR group. Patients in the RCR group were more prone to present with plaque rupture (24.1% vs 5.0%, p = 0.008). Cholesterol crystal (22.2% vs 12.5%, p = 0.226) and thin-cap fibroatheroma (25.9% vs. 12.5%, p = 0.109) were more common in the RCR group, though without statistical difference. Multivariate logistic regression showed that RCR (odds ratio [OR]: 7.95, p = 0.011) and smoking (OR: 4.08, p = 0.026) were independent risk factors of plaque rupture in our patients.

Conclusions: ACS patients with RCR are more likely to have atherosclerotic plaque and plaque rupture, indicating a more vulnerable plaque phenotype.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.atherosclerosis.2020.11.033DOI Listing
January 2021

MOVICS: an R package for multi-omics integration and visualization in cancer subtyping.

Bioinformatics 2020 Dec 14. Epub 2020 Dec 14.

State Key Laboratory of Natural Medicines, Research Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University, Nanjing, China.

Summary: Stratification of cancer patients into distinct molecular subgroups based on multi-omics data is an important issue in the context of precision medicine. Here we present MOVICS, an R package for multi-omics integration and visualization in cancer subtyping. MOVICS provides a unified interface for 10 state-of-the-art multi-omics integrative clustering algorithms, and incorporates the most commonly used downstream analyses in cancer subtyping researches, including characterization and comparison of identified subtypes from multiple perspectives, and verification of subtypes in external cohort using two model-free approaches for multiclass prediction. MOVICS also creates feature rich customizable visualizations with minimal effort. By analysing two published breast cancer cohort, we signifies that MOVICS can serve a wide range of users and assist cancer therapy by moving away from the 'one-size-fits-all' approach to patient care.

Availability And Implementation: MOVICS package and online tutorial are freely available at https://github.com/xlucpu/MOVICS.

Supplementary Information: Supplementary data are available at Bioinformatics online.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/bioinformatics/btaa1018DOI Listing
December 2020

Efficacy and Safety of Transcatheter vs. Surgical Aortic Valve Replacement in Low-to-Intermediate-Risk Patients: A Meta-Analysis.

Front Cardiovasc Med 2020 16;7:590975. Epub 2020 Nov 16.

Department of Cardiology, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.

The efficacy and safety of transcatheter aortic-valve replacement (TAVR) vs. surgical aortic valve replacement (SAVR) for low- to intermediate-surgical risk patients remains uninvestigated. We aimed to investigate the efficacy and safety of transcatheter aortic-valve replacement (TAVR) vs. surgical aortic valve replacement (SAVR) for low-intermediate surgical risk patients. PubMed, Cochrane Library, and Embase databases were searched to identify potential references. Only randomized controlled trials (RCTs) or observational studies using propensity score matching were eligible for screening. The primary endpoint was all-cause death. The secondary outcomes were bleeding, stroke, myocardial infarction (MI), and other complications of aortic-valve replacement. In addition, we performed subgroup analysis based on surgical risk and study type. Eight RCTs and 13 observational studies covering 12,467 patients were included in the current meta-analysis. For patients with low-surgical risk, compared with SAVR, TAVR was found to be associated with a lower mortality at a follow-up period of 1 year (odds ratio, OR: 0.66, 95% CI: [0.46, 0.96], = 0.03). This benefit disappeared when the follow-up was extended to 2 years (OR: 0.89, 95% CI: [0.61, 1.30], = 0.56). For patients with intermediate-surgical risk, TAVR showed to have similar mortality with SAVR regardless of follow-up period (30-day, 1-year, or 2-year). TAVR could reduce the incidence of bleeding, AF, and AKI. For complications, such as MI and stroke, TAVR exhibited to have similar safety with SAVR. However, TAVR was found to be associated with a higher incidence of reintervention, major vascular complication, paravalvular leak, and PPI. For patients with a low-to-intermediate surgical risk, TAVR has at least an equivalent clinical effect to SAVR for 2 years after the procedure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcvm.2020.590975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7701058PMC
November 2020

Nivolumab in combination with anlotinib achieved remarkable efficacy in a patient with driver-negative lung squamous cell carcinoma and PS of 4.

Ann Palliat Med 2020 Nov;9(6):4384-4388

Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, Nanjing, China.

Patients with driver-negative non-small cell lung cancer (NSCLC) and performance status (PS) of 3-4 do not tolerate chemotherapy well. There is currently no suitable treatment plan, and best supportive care is offered to patients with PS of 3 or greater. Some retrospective studies have shown the poor efficacy of immune checkpoint inhibitors (ICIs) for advanced NSCLC patients with PS ≥2 regardless of PD-L1 expression. However, some recent studies suggest that the anti-angiogenic drug has an immunomodulatory effect and can enhance immune efficacy. Here, we report a 72-year-old male patient with a diagnosis of driver-negative lung squamous cell carcinoma with respiratory failure and other serious medical conditions, resulting in PS of 4. We tried administering nivolumab (immune checkpoint inhibitor, ICI) in combination with anlotinib (angiogenic inhibitor) treatment to the patient. After 2 months of combination treatment, improved PS and a partial response (PR) was observed. Presently, the patient is on regular follow-up for over 13 months without any evidence of disease progression or distant metastasis. Our successful treatment of this driver-negative lung squamous cell carcinoma patient provides optimistic data to support the synergistic effect of immunotherapy and anti-angiogenesis therapy, and also demonstrated the potential application of this treatment regimen in critically ill patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/apm-20-2096DOI Listing
November 2020

A randomized comparison of a novel iopromide-based paclitaxel-coated balloon Shenqi versus SeQuent Please for the treatment of in-stent restenosis.

Coron Artery Dis 2020 Nov 20. Epub 2020 Nov 20.

Department of Cardiology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai.

Background: Treatment of coronary in-stent restenosis (ISR) remains challenging in contemporary clinical applications. Drug-coated balloon (DCB) angioplasty offers an effective treatment for ISR. Shenqi is a novel iopromide-based paclitaxel-coated balloon and its clinical safety, effectiveness and angiographic efficacy in patients with ISR have not been investigated.

Methods: A total of 216 subjects with the first occurrence of ISR at 11 investigational sites in China were randomly allocated in a 1:1 fashion to treatment with DCB SeQuent Please or Shenqi. Clinical follow-up was planned at 1, 6, 9 and 12 months, and angiographic follow-up was planned at 9 months. The study was powered for the primary endpoint of 9-month in-segment late loss.

Results: At 9-month follow-up, the in-segment late loss was 0.29 ± 0.43 mm with Shenqi versus 0.30 ± 0.46 mm with SeQuent Please, and the one-sided 97.5% upper confidence limit of the difference was 0.14 mm, achieving noninferiority of Shenqi compared with SeQuent Please (P = 0.002). In total, 12 patients developed target lesion failure (TLF) in the Shenqi group compared with 16 patients in the SeQuent Please group (10.91% versus 15.09%; P = 0.42) within 1 year. TLF was mainly driven by target lesion revascularization (9.09%) followed by target vessel-related myocardial infarction (1.82%) and cardiovascular death (0.91%) in the Shenqi group.

Conclusions: Shenqi DCB was noninferior to SeQuent Please DCB for the primary endpoint of 9-month in-segment late loss. Shenqi DCB may become an attractive alternative treatment for patients with coronary ISR, withholding the need for additional stent implantation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MCA.0000000000000994DOI Listing
November 2020

Prognostic impact of the atherogenic index of plasma in type 2 diabetes mellitus patients with acute coronary syndrome undergoing percutaneous coronary intervention.

Lipids Health Dis 2020 Nov 16;19(1):240. Epub 2020 Nov 16.

Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing Key Laboratory of Precision Medicine of Coronary Atherosclerotic Disease, Clinical Center for Coronary Heart Disease, Capital Medical University, Beijing, 100029, China.

Background: The association of the atherogenic index of plasma (AIP), an emerging lipid index that can predict the risk for cardiovascular disease, with adverse outcomes in type 2 diabetes mellitus (T2DM) patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) has not been determined. Therefore, the aim of this study was to investigate whether the AIP could independently predict adverse cardiovascular events in T2DM patients with ACS undergoing PCI.

Methods: This study was a retrospective analysis of a single-centre prospective registry involving 826 consecutive T2DM patients who underwent primary or elective PCI for ACS from June 2016 to November 2017. This study ultimately included 798 patients (age, 61 ± 10 years; male, 72.7%). The AIP was calculated as the base 10 logarithm of the ratio of the plasma concentration of triglycerides to high-density lipoprotein-cholesterol (HDL-C). All the patients were divided into 4 groups based on the AIP quartiles. The primary endpoint was a composite of death from any cause, non-fatal spontaneous myocardial infarction (MI), non-fatal ischaemic stroke, and unplanned repeat revascularization. The key secondary endpoint was a composite of cardiovascular death, non-fatal MI, and non-fatal ischaemic stroke.

Results: During a median follow-up period of 927 days, 198 patients developed at least one event. An unadjusted Kaplan-Meier analysis showed that the incidence of the primary endpoint increased gradually with rising AIP quartiles (log-rank test, P = 0.001). A multivariate Cox proportional hazards analysis revealed that compared with the lowest AIP quartile, the top AIP quartile was associated with significantly increased risk for the primary and key secondary endpoints (hazard ratio [HR]: 2.249, 95% confidence interval [CI]: 1.438 to 3.517, P < 0.001; and HR: 2.571, 95% CI: 1.027 to 6.440, P = 0.044, respectively).

Conclusions: A higher AIP value on admission was independently and strongly associated with adverse cardiovascular events in T2DM patients with ACS undergoing PCI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12944-020-01418-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667811PMC
November 2020

Variants in Familial Hypercholesterolemia: A Comprehensive Synopsis.

Front Genet 2020 23;11:1020. Epub 2020 Sep 23.

Beijing Key Laboratory of Precision Medicine of Coronary Atherosclerotic Disease, Department of Cardiology, Beijing Anzhen Hospital, Clinical Center for Coronary Heart Disease, Beijing Institute of Heart Lung and Blood Vessel Disease, Capital Medical University, Beijing, China.

Autosomal dominant familial hypercholesterolemia (FH) affects approximately 1/250, individuals and potentially leads to elevated blood cholesterol and a significantly increased risk of atherosclerosis. Along with improvements in detection and the increased early diagnosis and treatment, the serious burden of FH on families and society has become increasingly apparent. Since FH is strongly associated with proprotein convertase subtilisin/kexin type 9 (), increasing numbers of studies have focused on finding effective diagnostic and therapeutic methods based on . At present, as is one of the main pathogenic FH genes, its contribution to FH deserves more explorative research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fgene.2020.01020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538608PMC
September 2020

A path-choice-based biosensor to detect the activity of the alkaline phosphatase as the switch.

Anal Chim Acta 2020 Oct 27;1135:64-72. Epub 2020 Aug 27.

School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Institute of Reproductive Health/Center of Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. Electronic address:

Alkaline phosphatase (ALP), which converts the phosphate group (-PO) in the substrate to the hydroxyl group (-OH), is a useful tool in the biological analysis, a good indicator of dissolved inorganic phosphorus levels and an important biomarker for several diseases. In conventional designs for ALP detection, both the interferent with a -PO and the target with a -OH will go into the sensing path and give out the undesired background and the desired signal respectively. This limited the sensitivity of the method and required the complicated design to achieve a satisfying limit of detection (LOD) of ALP. Here, we provided a new sensing strategy for ALP detection design. We designed a path-choice-based biosensor with two DNA tracks in which ALP works as the switch to guide the reaction path of lambda exonuclease (λ exo). The path-choice character enlarged the difference between signal and background by separating the interferent removing path and the target sensing path. The substrate preference of ALP and λ exo was studied to optimize the structure of DNA tracks. The path-choice-based biosensor achieved simple, fast (30 min), sensitive (LOD 0.014 U L) and selective detection of the activity of ALP. The method has been applied to detect the activity of ALP in cell lysates, which shows the potential application in ALP-related biological research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.aca.2020.08.040DOI Listing
October 2020

Sodium-glucose cotransporter 2 inhibitors and fracture risk in patients with type 2 diabetes mellitus: a meta-analysis of randomized controlled trials.

Ther Adv Chronic Dis 2020 26;11:2040622320961599. Epub 2020 Sep 26.

Department of Cardiology, Beijing Anzhen Hospital, Beijing Institute of Heart Lung and Blood Vessel Disease, Capital Medical University, Anzhen Road, Chaoyang District, Beijing 100029, China.

Background: Patients with type 2 diabetes mellitus (T2DM) have an increased risk of fracture compared with those without T2DM. Some oral glucose-lowering agents may increase the incidence of fracture. Whether sodium-glucose co-transporter 2 inhibitors (SGLT2is) are associated with increased risk of fracture remains unclear.

Methods: We retrieved articles from database, and other sources up to 24 October 2019. We included randomized controlled trials (RCTs) that reported fractures and analyzed the fracture incidence of SGLT2i, canagliflozin, dapagliflozin, and empagliflozin. Subgroup analysis was also performed based on baseline characteristics.

Results: A total of 78 RCTs with 85,122 patients were included in our analysis. The overall SGLT2i fracture incidence was 2.56% 2.77% in the control group [odds ratio (OR), 1.03; 95% confidence interval (CI) (0.95, 1.12);  = 0.49]. Compared with the control treatment, treatment with canagliflozin led to a higher rate of fractures [OR, 1.17; 95% CI (1.00, 1.37);  = 0.05], but no significant difference was observed when compared with dapagliflozin [OR, 1.02; 95% CI (0.90, 1.15);  = 0.79] or empagliflozin [OR, 0.89; 95% CI (0.73, 1.10);  = 0.30]. Subgroup analysis showed that, in a follow-up of less than 52 weeks, SGLT2i decreased the incidence of fracture by 29% [OR, 0.71; 95% CI (0.55, 0.93);  = 0.01], but this benefit was lost when the follow-up extended to more than 52 weeks [OR, 1.08; 95% CI (0.98, 1.18);  = 0.12].

Conclusion: Canagliflozin seems to increase the risk of fracture, while other SGLT2is do not result in a higher incidence of fracture.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2040622320961599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7534105PMC
September 2020

The Efficacy and Safety of First-Line Chemotherapy in Patients With Non-small Cell Lung Cancer and Interstitial Lung Disease: A Systematic Review and Meta-Analysis.

Front Oncol 2020 8;10:1636. Epub 2020 Sep 8.

Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, Nanjing, China.

Lung cancer is a well-known comorbidity of interstitial lung disease (ILD), and the actual efficacy and safety of chemotherapy for patients with non-small cell lung cancer and interstitial lung disease (NSCLC-ILD) have not been determined. We conducted this meta-analysis to assess the efficacy and safety of chemotherapy for patients with NSCLC-ILD. We searched related studies from the Cochrane Library, PubMed, and Embase. The endpoints were objective response rate (ORR), disease control rate (DCR), 1-year overall survival rate (1-yOS rate), and first-line chemotherapy-related acute exacerbation of interstitial lung disease rate (AE-ILD rate). We included 21 studies involving 684 patients in our analysis. The pooled ORR was 43% (95% CI: 38.0-49.0%), and the pooled DCR was 80.0% (95% CI: 75.7-83.9%). The modified overall 1-yOS rate was 33.0% (95% CI: 29.0-37.0%). The pooled AE-ILD rate was 8.07% (95% CI: 6.12-10.26%). Subgroup analysis revealed a trend for lower AE-ILD rate (4.98%; 95% CI: 2.44-8.37%) in patients with carboplatin plus nab-paclitaxel. Lung function and AE-ILD may be associated with the prognosis of patients with NSCLC-ILD. First-line chemotherapy is effective in patients with NSCLC-ILD, and the AE-ILD rate is acceptable, but the prognosis is limited. Future randomized controlled trials are needed to explore more appropriate treatment regimens to improve the prognosis of patients with NSCLC-ILD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.01636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506119PMC
September 2020