Identifying critical genes and pathways of doxorubicin-induced cardiomyopathy via bioinformatics analysis.

OBJECTIVE: The pathogenesis of doxorubicin (DOX) induced cardiomyopathy (DCM) is still uncertain. We aimed to identify the critical genes and pathways involved in DCM based on bioinformatics analysis. MATERIALS AND METHODS: The GSE59672 and GSE23598 mice heart tissue microarray data were obtained from Gene Expression Omnibus (GEO) database. The "limma" package of R software was used to screen the differently expressed genes (DEGs). GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses were performed on DEGs by using "clusterProfiler" package in R software. The PPI (Protein - Protein Interaction) network of DEGs constructed by STRING online database and thereby the top 15 hub genes selected by cytoHubba in Cytoscape software. The hub genes interaction was performed by GeneMANIA online database. The "Corrplot" R package was employed to assess hub genes correlation. RESULTS: Finally, a total of 492 and 501 DEGs were screened in GSE59672 and GSE23598 datasets, respectively. GO analyses revealed that DEGs were mainly involved in the regulation of extracellular matrix organization, metabolic process, regulation of collagen-containing extracellular matrix. KEGG pathway analyses indicated that DEGs were mainly involved in protein digestion and absorption, ECM-receptor interaction, phagosome, and p53 signaling pathway. Finally, the 8 hub genes were identified, including Col1a1, Col3a1, Col1a2, Col6a1, Ptprc, Tyrobp, Itgb2, and Ctss. CONCLUSIONS: The present study identified a series of key genes, including Col1a1, Col3a1, Col1a2, Col6a1, Ptprc, Tyrobp, Itgb2, and Ctss. In addition, important pathways were also discovered. The results of this study may provide a novel molecular mechanism and potential therapeutic targets for DCM.

The top 100 most cited articles on intramedullary nail fixation from 2018-2022: a bibliometric and visualized analysis.

OBJECTIVE: Intramedullary nails are commonly used for the purposes of internal fixation in the repair of tubular bone fractures, allowing for optimal fixation while minimizing intraoperative bleeding, surgical incision size, and associated stress. These nails are thus often utilized to repair hip and peripheral fractures, femur fractures, tibial fractures, humerus fractures, and clavicle fractures. Recent life expectancy increases, rising economic standards, and technological innovations have led to the application of a wider range of materials and techniques in the context of orthopedic device production, further expanding the clinical indications for intramedullary nailing. Despite the growing importance of this technique, there is currently a lack of any bibliometric or visual analyses that provide a robust overview of recent progress in the intramedullary nailing research space. Accordingly, this study was developed to succinctly and comprehensively summarize the current research status and major hotspots in this field through a bibliometric review of major relevant scientific articles focused on intramedullary nailing published in recent years. MATERIALS AND METHODS: For this analysis, the top 100 most-cited articles focused on intramedullary nails published between 2018 and 2022 were identified through a search of the Web of Science Core Collection database. Countries, institutions, journals, and other specific parameters associated with these articles were then analyzed using tools including CiteSpace, VOS-viewer, Origin, and SCImago Graphica in an effort to more clearly define the latest trends in the intramedullary nail-related research space. RESULTS: The top 3 most-cited articles related to intramedullary nailing over the past five years were "Antibacterial and immunogenic behavior of silver coatings on additively manufactured porous titanium", "Diaphyseal long bone nonunions - types, etiology, economics, and treatment recommendations", and "Epidemiology, treatment, and mortality of trochanteric and subtrochanteric hip fractures: data from the Swedish fracture register", all of which were published in 2018, respectively exhibiting 93, 83, and 81 citations. Of the 100 most-cited intramedullary nailing-related articles, 38, 20, and 12 were respectively published by researchers from the USA, China, and the UK, while research groups from Italy and Spain each published 7 articles. Four of this field's most highly cited articles were published by individuals affiliated with the US-based University of California System and the University System of Ohio. Of the 15 journals that published the largest number of these top 100 articles, the "Injury International Journal of The Care of The Injured" and the "Journal of Orthopaedic Trauma" published 9 manuscripts each, which was more than any other journal, while the "Journal of Orthopaedic Surgery" and the "Journal of Pediatric Orthopaedics" published 7 each. In total, 73 highly cited articles focused on utilizing intramedullary nailing in orthopedic applications. Rozbruch SR from the USA published 3 high-quality articles in this research space, while the Chinese researchers Chang Shi Min, Du Shou Chao, Hou Zhi Yong, and Hu Sun Jun exhibited a total linkage strength of 21 in global interaction analyses. The most common keywords associated with intramedullary nail-related research identified in these analyses included "Hip fracture", "Nonunion", "Limb lengthening", "Proximal humeral fractures", "Additive manufacturing", "Induced membrane", and "Endoprosthetic replacement". Promising areas of potential future research focus may include "Limb reconstruction", "Pediatric deformity", and "Congenital femoral deficiency". CONCLUSIONS: This analysis revealed that the highest volume of high-impact research output focused on intramedullary nailing over the past 5 years has been produced by the USA, followed by China and the UK. The most influential journals in this research space were Injury International Journal of The Care of The Injured and the Journal of Orthopaedic Trauma, while the institutions associated with the most highly cited articles were the University of California System and the University System of Ohio. Intramedullary nailing is commonly utilized to treat intertrochanteric fractures and other tubular bone fractures. In the future, the application of augmented and virtual reality technologies may help shorten the learning curve for orthopedic surgeons and trauma surgeons who are learning intramedullary nailing-related techniques, and the combination of intramedullary nailing with antibacterial drugs, metal alloys, 3D navigation, and sensor devices may help improve patient outcomes.

Different sedation profiles with ciprofol compared to propofol represented by objective sedation level assessments by BIS and its acute hemodynamic impact in 3 escalated doses of ciprofol and propofol in healthy subjects: a single-center, open-label, randomized, 2-stage, 2-way crossover trial.

OBJECTIVE: To compare the sedation profiles and the pharmacokinetic, pharmacodynamic and safety characteristics of ciprofol and propofol at 3 escalated dose levels in healthy Chinese male subjects. PATIENTS AND METHODS: Eighteen subjects were planned to be enrolled into 3 dose groups in turn: group 1 (ciprofol-0.4 mg/kg vs. propofol-2.0 mg/kg), group 2 (ciprofol-0.6 mg/kg vs. propofol-3.0 mg/kg) and group 3 (ciprofol-0.8 mg/kg vs. propofol-4.0 mg/kg). They were randomly assigned into a ciprofol or propofol group in a ratio of 1:1, with sequences of ciprofol-propofol or propofol-ciprofol, separated with a washout period of at least 48 h. RESULTS: A total of 19 subjects were enrolled and 18 completed the trial. The median time to being fully alert after induction by ciprofol was longer than for propofol. The bispectral index (BIS) recovered significantly slower with ciprofol than with propofol 5 min and 10 min after reaching its lowest points. Systolic blood pressure (group 1: p=0.041; group 2: p=0.015; group 3: p=0.004) and mean arterial pressures (group 1: p=0.026; group 2: p=0.015; group 3: p=0.004) measured by the area under the curve below the baseline during the 2 min after induction were significantly less for ciprofol compared to propofol, but a significant change in diastolic blood pressure was only observed in group 3 (p=0.002). Eighteen (100.0%) subjects experienced 47 ciprofol-related treatment emergent adverse events (TEAEs) and 17 (94.4%) subjects had 54 propofol-related TEAEs, which were mainly hypotension, involuntary movements, respiratory depression, and pain at the injection site with severity of grade 1 or 2. CONCLUSIONS: Ciprofol may be well tolerated at higher doses in the clinical practice and exhibited significantly different sedation profiles to propofol.

[Long term prognosis of fulminant myocarditis and predictors related to impaired cardiac function post discharge].

Objective: To compare the long-term prognosis of fulminant myocarditis (FM) and non-fulminant myocarditis (NFM) patients who survived and discharged from hospital, and to explore the factors associated with the long-term prognosis and impaired cardiac function. Methods: This study was a retrospective study. Consecutive patients with acute myocarditis hospitalized in Tongji Hospital from January 2017 to December 2020 were enrolled and divided into FM group and NFM group according to the type of myocarditis. Then, patients in the FM group were further divided into normal cardiac function group and impaired cardiac function group according the left ventricular ejection fraction (LVEF). All patients with acute myocarditis were treated with antiviral, immunomodulatory, immunosuppressive medications and symptomatic and supportive treatment, while FM patients were treated with comprehensive treatment plan. Clinical data at admission of enrolled patients were collected through the electronic medical record system. Patients were clinically followed-up at 1, 3, 6 and 12 months, then once a year after discharge by clinical visit. The primary endpoints included major cardiovascular events, impaired cardiac function was defined by LVEF<55%. Kaplan-Meier survival curve was used to analyze the occurrence of LVEF<55% and left ventricular enlargement during the follow-up of patients in FM group and NFM group, and Log-rank test was used for comparison between groups. Cox regression model was used to analyze the risk factors of impaired cardiac function in patients with FM during follow-up. Results: A total of 125 patients with acute myocarditis were enrolled (66 in FM group and 59 in NFM group). Compared with NFM group, the proportion of FM patients with the lowest LVEF<55% during hospitalization was higher (P<0.01), and the recovery time of normal LVEF during hospitalization was longer (P<0.01). The proportion of LVEF<55% at discharge was similar between the two groups (P=0.071). During the follow-up of 12 (6, 24) months, 1 patient (1.5%) died due to cardiac reasons in FM group after discharge, 16 patients (24.2%) had sustained LVEF<55% after discharge, and 8 patients (12.1%) had left ventricular enlargement. In NFM group, 3 patients (5.1%) had sustained LVEF<55%, and 1 patient (1.7%) had left ventricular enlargement. Kaplan-Meier survival curve analysis showed that the incidence of sustained LVEF<55% in FM group was higher than that in NFM group (P=0.003), and the incidence of left ventricular enlargement was also higher than that in NFM group (P=0.024). Subgroup analysis of patients in the FM group showed that, compared with the normal cardiac function group, the time from onset to admission was shorter (P=0.011), the proportion of LVEF<55% at discharge was higher (P=0.039), the proportion of coronary angiography was higher (P=0.014), and the LVEF recovery time during hospitalization was longer (P=0.036) in FM patients with impaired cardiac function. Multivariate Cox regression analysis showed that longer LVEF recovery time during hospitalization was an independent risk factor for cardiac function impairment after discharge of FM patients (HR=1.199, 95%CI 1.023-1.406, P=0.025). Conclusions: The incidence of reduced LVEF is significantly higher in FM patients than that in NFM patients. Longer LVEF recovery time during hospitalization is an independent risk factor for cardiac function impairment in FM patients after discharge.

[Risk stratification and low-density lipoprotein cholesterol goal attainment rates in patients with very high-risk or extreme high-risk atherosclerotic cardiovascular diseases regarding three guidelines].

Objective: To explore the differences of risk stratification of very high-risk or extreme high-risk atherosclerotic cardiovascular diseases (ASCVD) and the attainment rates of low-density lipoprotein cholesterol (LDL-C) management targets evaluated by three different criteria, and the causal attributions of these differences. Methods: Patients with ASCVD were consecutively enrolled from January 1 to December 31 in 2019, and were evaluated for very high-risk or extreme high-risk and LDL-C goal attainment rates with 2018 American guideline on the management of blood cholesterol (2018AG), 2019 China Cholesterol Education Program (CCEP) Expert Advice for the management of dyslipidemias (2019EA) and 2020 Chinese expert consensus on lipid management of very high-risk ASCVD patients(2020EC), respectively. The causal attributions of the differences in attainment rates were analyzed as well. Results: A total of 1 864 ASCVD patients were included in this study. According to 2018AG, 2019EA and 2020EC, the proportions of the patients with very high-risk or extreme high-risk were 59.4%, 90.7%, and 65.6%, respectively. The absolute LDL-C target attainment rates were 37.2%, 15.7%, and 13.7%, respectively, the differences between each two rates were statistically significant (all P<0.001). As to the differences in attainment rates between 2020EC and 2018AG, 61.5% were due to the different LDL-C goal attainment values and 38.5% were caused by the different risk stratifications, while for the differences between 2020EC and 2019EA attainment rates, different LDL-C goal attainment values were responsible for 13.2%, and different risk stratifications were responsible for 86.8% of the differences. Conclusions: There are significant differences in the proportions and LDL-C attainment rates among the three different criteria for very high-risk or extreme high-risk ASCVD. 2020EC showed a moderate proportion of patients with extreme high-risk, and had the lowest LDL-C attainment rate. The differences between 2020EC and 2018AG are mainly due to the LDL-C target values, and the differences between 2020EC and 2019EA are mainly caused by the risk stratifications.

[Clinical characteristics and prognosis of young (<35 years) patients with acute ST-segment elevation myocardial infarction].

Objective: To analyze the risk factors and clinical characteristics as well as long-term prognosis of young patients (aged 18-35 years) with acute ST-segment elevation myocardial infarction (STEMI). Methods: In this retrospective study, from January 2007 to December 2017, STEMI patients who were hospitalized in Beijing Anzhen Hospital, Capital Medical University and younger than 45 years old were collected. Patients were divided to the 18-35 years old group and 36-44 years old group. The basic information of patients, clinical laboratory results, surgical information and discharge diagnosis of enrolled patients were extracted from the electronic medical record system. Subgroup analysis on STEMI patients aged 18 to 35 years was performed to compare the clinical features and outcome of patients with normal coronary angiography or stenotic coronary angiography. Results: 496 patients (20.3%) were between 18 and 35 years old, 480 cases (96.8%) were men, and 371 cases (74.8%) were smokers. The proportion of hypertension and diabetes was lower, but percent of obese (122 cases (43.3%)), level of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), uric acid and homocysteine ​​(Hcy) were significantly higher in patients aged 18 to 35 years compared with STEMI patients aged 36 to 44 years (all P<0.05). In the 18-35 years old group, there were 53 patients (10.7%) with normal coronary angiography and 443 patients (89.3%) with stenosis. The age, proportion of hypertension and diabetes, TC, LDL-C, and triglyceride (TG) levels were lower in the normal coronary angiography group than those in the coronary artery stenosis group (all P<0.05). The main coronary artery lesions were single vessel lesions (263 cases (59.4%)), and the main culprit vessels were left anterior descending artery lesions (238 cases (53.7%)). The follow-up time was 7.0 (4.0, 10.0) years, cardiovascular events were reported in 62 patients (18.9%), of which 14 patients (3.2%) died. The survival rate of patients without cardiovascular events in normal coronary angiography group was higher than that in stenosis group (P=0.029). Multivariate Cox regression analysis showed that diabetes (HR=2.713, 95%CI 1.479-4.976, P=0.001) and dyslipidemia (HR=2.819, 95%CI 1.564-5.079, P=0.001) were independent risk factors for recurrence of cardiovascular events in adult STEMI patients aged 18 to 35 years. Conclusions: STEMI patients aged 18 to 35 years were featured by male sex, obese and smokers. The proportion of hypertension and diabetes was low, while the levels of LDL-C, uric acid and Hcy were high in these patients. Coronary artery stenosis was common, and the stenosis was more likely to occur in the left anterior descending branch. Patients with normal coronary angiography had a better prognosis than those with stenosis. Diabetes and hyperlipidemia increased the risk of recurrent cardiovascular events.

LncRNA HOXA11-AS promotes cell growth by sponging miR-24-3p to regulate JPT1 in prostate cancer.

OBJECTIVE: Long noncoding RNA (lncRNA) was found to play crucial roles in regulating cancer progression. HOXA11 antisense RNA (HOXA11-AS) was reported to serve an oncogenic lncRNA in cancers but its role in prostate cancer (PCa) remains to be explored. MATERIALS AND METHODS: Expression levels of HOXA11-AS in PCa tissues and cells were analyzed with quantitative Real-Time PCR method. MTT assay, colony formation assay, transwell invasion assay, and flow cytometry assay were conducted to explore the biological roles of HOXA11-AS in PCa. Rescue experiments were conducted to investigate mechanisms of HOXA11-AS in regulating PCa progression. RESULTS: We revealed that HOXA11-AS was upregulated in PCa. Silencing of HOXA11-AS significantly inhibited PCa cell proliferation, colony formation, invasion, and promoted apoptosis in vitro. On the contrary, forcing of HOXA11-AS expression caused opposite effects on cancer cell behaviors. Furthermore, we showed that HOXA11-AS1 serves as a competing endogenous RNA (ceRNA) to regulate Jupiter microtubule associated homolog 1 (JPT1) via sponging microRNA-24-3p (miR-24-3p). Functionally, the overexpression of miR-24-3p or knockdown of JPT1 could partially reverse the effects of HOXA11-AS overexpression on PCa cell behaviors. CONCLUSIONS: This newly identified HOXA11-AS/miR-24-3p/JPT1 axis may provide novel angle for the better control of PCa.

[Difference on prevalence and trends of conventional risk factors for ASCVD between young Chinese and American adults with first acute myocardial infarction].

Objective: This study aimed to compare the prevalence and trends of conventional risk factors for atherosclerotic cardiovascular disease(ASCVD) between young Chinese and American adults with first acute myocardial infarction. Methods: This was a retrospective cohort analysis. Hospitalized yang adults (aged from 18 to 44 years old) with first acute myocardial infarction(AMI) from January 2007 through December 2017 were identified from Beijing Anzhen hospital medical record system. Prevalence and trends of hypertension, diabetes mellitus, obesity, smoking, and dyslipidemia were analyzed and compared with young American adults, whose data were reported by Yandrapalli et al, and the hospitalizations for a first AMI in young adults aged 18 to 44 years were identified from national inpatient sample from January 2005 through September 2015. Results: Chinese cohort included 2 866 young adults with a first AMI (male, n=2 739, female, n=127), the mean age was (39±5) years. Presentation of AMI was more frequently ST-segment elevation myocardial infarction (77.3%, 2 214/2 866). American cohort included 280 875 subjects (male, n=203 700, female, n=77 175), the mean age was 39±5 years. Presentation of AMI was more frequently non-ST-segment elevation myocardial infarction (53.6%, 150 549/280 875). In China, dyslipidemia 2 254 (78.6%), smoking 2 084(72.7%), and hypertension 1 170 (40.8%) were most prevalent, and 96.0% (2 752/2 866) of patients had at least 1 risk factor; in the United States, smoking 159 537(56.8%), dyslipidemia 145 212 (51.7%), and hypertension 139 876 (49.8%) were most prevalent, and 90.3% (253 630/280 875) of patients had at least 1 risk factor. Women had a prevalence of diabetes was higher in women, and prevalence of dyslipidemia and smoking was higher in men in China (all P<0.05);prevalence of obesity, diabetes and hypertension was higher in Women, and prevalence of dyslipidemia and smoking was higher in man in the United States (all P<0.001). Prevalence of dyslipidemia and smoking was higher Chinese men (79.3% vs. 54.6%, 75.5% vs. 58.1%,all P<0.001), and prevalence of obesity, diabetes and hypertension was lower (13.1% vs. 18.6%, 14.9% vs. 19.9%, 40.6% vs. 49.3%, all P<0.001)in Chinses cohort than those in the United States cohort. Prevalence of smoking and obesity was lower (12.6% vs. 53.4%, 10.2% vs. 26.9%, all P<0.001) and prevalence of dyslipidemia was higher (63.8% vs. 44.1% P<0.001) in Chinese women than those in the United States women. Patients presenting with non-ST-segment elevation myocardial infarction had a higher prevalence of obesity, diabetes and hypertension than patients presenting with ST-segment elevation myocardial infarction in China (20.1% vs.10.9%, 17.6% vs. 14.5%, 47.4% vs. 38.9%, all P<0.05). The prevalence of the three risk factors also was higher in patients presenting with non-ST-segment elevation myocardial infarction in the US (24.0% vs.17.0%, 25.0% vs. 20.0%, 54.6% vs. 44.2%, all P<0.001), prevalence of smoking and dyslipidemia was lower in these patients (53.5% vs. 60.5%,51.4% vs. 52.1%, all P<0.001). The prevalence of hypertension and obesity increased and the rate of smoking reduced in China from 2007 through 2017 (all trend P<0.001). The prevalence of all these five conventional risk factors increased temporally in the United States from 2005 to 2015 (all trend P<0.001). The prevalence of hypertension increased by 15.6% in China and 14.5% in the United States, respectively, accounting the largest increase. Conclusions: Smoking, dyslipidemia, and hypertension are most prevalent in China and United State. Significant sex and AMI subtype difference are observed for individual risk factors. The prevalence of hypertension and obesity increased significantly over time in China and all these five conventional risk factors increased significantly in the United States.

[Gender differences in risk factors and characteristics of young patients hospitalized for first acute coronary syndrome].

Objective: To analyze the characteristics of modifiable risk factors, coronary artery lesions, reperfusion and drug treatment in young women hospitalized for first acute coronary syndrome (ACS). Methods: Clinical data of young adults of 18 to 44 years hospitalized for first ACS in Beijing Anzhen Hospital between January 2007 and December 2017 were analyzed. A total of 7 106 young adults with ACS were enrolled, 6 593(92.8%) were male and 513(7.2%) were female. There were 2 254(31.7%) patients with ST-segment elevation myocardial infarction (STEMI), 704(9.9%) patients with non-ST-segment elevation myocardial infarction (NSTEMI) and 4 148(58.4%) patients with unstable angina (UA). Clinical characteristics, laboratory examinations, coronary angiography and medical treatment were recorded. The gender differences in the characteristics of modifiable risk factors and coronary artery stenosis in young patients with ACS were also analyzed. Results: Dyslipidemia (87.5%) followed by overweight/obese(83.8%) and smoking (68.5%) were most prevalent modifiable risk factors in men. Dyslipidemia (63.4%), overweight/obese (63.4%) and hypertension (45.5%) were most prevalent modifiable risk factors in women. The prevalence rates of at least 1 risk factor in men and women patients were 99.1% and 87.9%, respectively. Between 2007 and 2017, the rates of hypertension and overweight/obese in men increased, and the rates of dyslipidemia and smoking decreased (trend P<0.01). The changes of incidence of modifiable risk factors through the years in women were not statistically significant. The rate of men receiving coronary angiography was higher than that in women (96.6% vs 93.4%, P<0.01). Women were more likely to suffer left main coronary artery disease than men (7.3% vs 4.1%, P<0.01). Multi-vessel coronary artery disease occurred more in men (43.4%), and single vessel coronary artery disease occurred more in women (47.0%). Women presented with STEMI had a lower probability of receiving clopidogrel/ticagrelor (76.8% vs 86.1%, P<0.01) and angiotensin Ⅰ-converting enzyme inhibitor/angiotonin receptor blocker (ACEI/ARB) (46.5% vs 60.2%, P<0.01) than that in men. Women presented with UA had a lower probability of receiving aspirin (86.3% vs 89.9%), clopidogrel/ticagrelor (69.7% vs 75.6%), statin (78.8% vs 85.0%) and ACEI/ARB (32.7% vs 38.6%) than men (all P<0.01). Women had a higher probability of presenting Killip II-IV than men (38.6% vs 25.6%, P<0.05). Conclusion: The majority of young patients with ACS were men. The prevalence rates of modifiable risk factors are very high in both man and woman. Compared with man, women with AMI are more likely to develop acute heart failure with lower probability of reperfusion and drug treatment.

Novel Cyclic Peptides from Lethal Amanita Mushrooms through a Genome-Guided Approach.

Most species in the genus Amanita are ectomycorrhizal fungi comprising both edible and poisonous mushrooms. Some species produce potent cyclic peptide toxins, such as α-amanitin, which places them among the deadliest organisms known to mankind. These toxins and related cyclic peptides are encoded by genes of the "MSDIN" family (named after the first five amino acid residues of the precursor peptides), and it is largely unknown to what extent these genes are expressed in the basidiocarps. In the present study, Amanita rimosa and Amanita exitialis were sequenced through the PacBio and Illumina techniques. Together with our two previously sequenced genomes, Amanita subjunquillea and Amanita pallidorosea, in total, 46 previously unknown MSDIN genes were discovered. The expression of over 80% of the MSDIN genes was demonstrated in A. subjunquillea. Through a combination of genomics and mass spectrometry, 12 MSDIN genes were shown to produce novel cyclic peptides. To further confirm the results, three of the cyclic peptides were chemically synthesized. The tandem mass spectrometry (MS/MS) spectra of the natural and the synthetic peptides shared a majority of the fragment ions, demonstrating an identical structure between each peptide pair. Collectively, the results suggested that the genome-guided approach is reliable for identifying novel cyclic peptides in Amanita species and that there is a large peptide reservoir in these mushrooms.

[Risk factor distribution features and trends of young adults with first acute coronary syndrome].

Objective: To observe the characteristics and trends during the last 11 years of risk factors of young adults with first acute coronary syndrome (ACS). Methods: It was a cross-sectional study. We included young adults (18 to 44 years old) hospitalized for acute coronary syndrome in Beijing Anzhen Hospital for a first time from January 2007 to December 2017. Acute coronary syndromes include ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI), and unstable angina (UA). The general information, medical history and laboratory test were recorded. Risk factors of ACS were smoking, dyslipidemia, overweight/obesity, hypertension and diabetes. Results: Data from 7 106 patients were analyzed, mean age was (39.8±4.2) years old and 6 593(92.8%)were men, including 2 254 (31.7%) STEMI, 704 (9.9%) NSTEMI and 4 148 (58.4%) UA. Most patients were male (6 593(92.8%)). Dyslipidemia (85.8%(6 094/7 106)), overweight/obesity (82.3%(5 850/7 106)), and smoking (63.9%(4 545/7 106)) were most prevalent. 98.3% (6 885/7 106) patients had at least 1 risk factor. The prevalence of hypertension, diabetes and overweight/obesity increased from 2007 to 2017. Rates of hypertension increased from 37.1%(111/299) to 48.1%(498/1 035) (Ptrend<0.01), diabetes from 12.0%(36/299) to 19.4%(201/1 035) (Ptrend<0.01), overweight/obesity from 74.2%(222/299) to 83.9%(868/1 035) (Ptrend<0.05), respectively. Conclusions: Dyslipidemia, overweight/obesity and smoking are most prevalent risk factors in young adults with a first ACS and most patients have at least 1 risk factor for ACS. Rates of hypertension, diabetes and overweight/obesity progressively increases over time in this patient cohort.

Zeb1 Promotes Odontoblast Differentiation in a Stage-Dependent Manner.

A comprehensive study of odontoblastic differentiation is essential to understand the process of tooth development and to achieve the ability of tooth regeneration in the future. Zinc finger E-box-binding homeobox 1 (Zeb1) is a transcription factor expressed in various neural crest-derived tissues, including the mesenchyme of the tooth germ. However, its role in odontoblastic differentiation remains unknown. In this study, we found the expression of Zeb1 gradually increased during odontoblast differentiation in vivo, as well as during induced differentiation of cultured primary murine dental papilla cells (mDPCs) in vitro. In addition, the differentiation of mDPCs was repressed in Zeb1-silenced cells. We used RNA sequencing (RNA-seq) to identify the transcriptome-wide targets of Zeb1 and used assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) to explore the direct targets of Zeb1 in both the early stage (embryonic day 16.5; E16.5) and the late stage (postnatal day 0; PN0) of tooth development. We identified the motifs of transcription factors enriched in Zeb1-dependent accessible chromatin regions and observed that only in the early stage of mDPCs could Zeb1 significantly change the accessibility of chromatin regions. In vivo and in vitro experiments confirmed that silencing of Zeb1 at E16.5 inhibited dentinogenesis. Analysis of RNA-seq and ATAC-seq resulted in the identification of Runx2, a gene directly regulated by Zeb1 during early odontoblast differentiation. Zeb1 enhances the expression of Runx2 by binding to its cis-elements, and ZEB1 interacts with RUNX2. In the late stage of tooth development, we found that ZEB1 could directly bind to and increase the enhancer activity of an element upstream of Dspp and promote dentinogenesis. In this study, for the first time, we revealed that ZEB1 promoted odontoblast differentiation in the early stage by altering chromatin accessibility of cis-elements near genes such as Runx2, while in the late stage, it directly enhanced Dspp transcription, thereby performing a dual role.

17ß-Estradiol improves osteoblastic cell function through the Sirt1/NF-κB/MMP-8 pathway.

Objective: This study aims to investigate the beneficial effects of 17ß-estradiol supplementation on the function of osteoblastic cells through the Sirtuin-1/nuclear transcription factor-κB/matrix metalloproteinase-8 (Sirt1/NF-κB/MMP-8) pathway.Methods: Mouse primary osteoblasts were obtained from neonatal mouse calvaria, and the cells were treated with or without 17ß-estradiol. We first detected the effect of 17ß-estradiol on the function of osteoblastic cells. Then, the changes in estrogen receptor-α (ERα), Sirt1, NF-κB, and MMP-8 were determined after the osteoblasts were treated with 17ß-estradiol. During supplementation with 17ß-estradiol, knockdown of Sirt1 in osteoblasts was used to further measure the changes of NF-κB and MMP-8 and observe the cell function.Results: In primary osteoblastic cells, exposure to 17ß-estradiol improved cell viability and increased the levels of bone formation biomarkers, including osteocalcin, osteoprotegerin (OPG), procollagen type 1 N-terminal propeptide (P1NP), and alkaline phosphatase (ALP). In addition, 17ß-estradiol supplement activated ERα and Sirt1 expression and inhibited NF-κB and MMP-8 expression. Moreover, these effects induced by 17ß-estradiol were reversed by knockdown of Sirt1 in mouse primary osteoblasts.Conclusion: 17ß-Estradiol replacement therapy may treat postmenopausal osteoporosis by improving osteoblastic cell function via the Sirt1/NF-κB/MMP-8 pathway.

Genome of lethal Lepiota venenata and insights into the evolution of toxin-biosynthetic genes.

BACKGROUND: Genomes of lethal Amanita and Galerina mushrooms have gradually become available in the past ten years; in contrast the other known amanitin-producing genus, Lepiota, is still vacant in this aspect. A fatal mushroom poisoning case in China has led to acquisition of fresh L. venenata fruiting bodies, based on which a draft genome was obtained through PacBio and Illumina sequencing platforms. Toxin-biosynthetic MSDIN family and Porlyl oligopeptidase B (POPB) genes were mined from the genome and used for phylogenetic and statistical studies to gain insights into the evolution of the biosynthetic pathway. RESULTS: The analysis of the genome data illustrated that only one MSDIN, named LvAMA1, exits in the genome, along with a POPB gene. No POPA homolog was identified by direct homology searching, however, one additional POP gene, named LvPOPC, was cloned and the gene structure determined. Similar to ApAMA1 in A. phalloides and GmAMA1 in G. marginata, LvAMA1 directly encodes α-amanitin. The two toxin genes were mapped to the draft genome, and the structures analyzed. Furthermore, phylogenetic and statistical analyses were conducted to study the evolution history of the POPB genes. Compared to our previous report, the phylogenetic trees unambiguously showed that a monophyletic POPB lineage clearly conflicted with the species phylogeny. In contrast, phylogeny of POPA genes resembled the species phylogeny. Topology and divergence tests showed that the POPB lineage was robust and these genes exhibited significantly shorter genetic distances than those of the house-keeping rbp2, a characteristic feature of genes with horizontal gene transfer (HGT) background. Consistently, same scenario applied to the only MSDIN, LvAMA1, in the genome. CONCLUSIONS: To the best of our knowledge, this is the first reported genome of Lepiota. The analyses of the toxin genes indicate that the cyclic peptides are synthesized through a ribosomal mechanism. The toxin genes, LvAMA1 and LvPOPB, are not in the vicinity of each other. Phylogenetic and evolutionary studies suggest that HGT is the underlining cause for the occurrence of POPB and MSDIN in Amanita, Galerina and Lepiota, which are allocated in three distantly-related families.

Vitamin B6 catabolism and lung cancer risk: results from the Lung Cancer Cohort Consortium (LC3).

BACKGROUND: Increased vitamin B6 catabolism related to inflammation, as measured by the PAr index (the ratio of 4-pyridoxic acid over the sum of pyridoxal and pyridoxal-5'-phosphate), has been positively associated with lung cancer risk in two prospective European studies. However, the extent to which this association translates to more diverse populations is not known. MATERIALS AND METHODS: For this study, we included 5323 incident lung cancer cases and 5323 controls individually matched by age, sex, and smoking status within each of 20 prospective cohorts from the Lung Cancer Cohort Consortium. Cohort-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between PAr and lung cancer risk were calculated using conditional logistic regression and pooled using random-effects models. RESULTS: PAr was positively associated with lung cancer risk in a dose-response fashion. Comparing the fourth versus first quartiles of PAr resulted in an OR of 1.38 (95% CI: 1.19-1.59) for overall lung cancer risk. The association between PAr and lung cancer risk was most prominent in former smokers (OR: 1.69, 95% CI: 1.36-2.10), men (OR: 1.60, 95% CI: 1.28-2.00), and for cancers diagnosed within 3 years of blood draw (OR: 1.73, 95% CI: 1.34-2.23). CONCLUSION: Based on pre-diagnostic data from 20 cohorts across 4 continents, this study confirms that increased vitamin B6 catabolism related to inflammation and immune activation is associated with a higher risk of developing lung cancer. Moreover, PAr may be a pre-diagnostic marker of lung cancer rather than a causal factor.

Correlation between peripheral skeletal muscle functions and the stable phase of COPD in older patients.

OBJECTIVE: To establish normal values for detection indexes of peripheral skeletal muscle dysfunction (quadriceps femoris) of healthy older subjects, and investigate the functional status of the peripheral skeletal muscle of patients with stable phase COPD. PATIENTS AND METHODS: Patients with stable phase COPD and healthy subjects of similar age were included. The assessments of strength and myoelectricity of the quadriceps femoris were recorded. The twitch tension of the quadriceps femoris (TwQ), quadriceps maximum voluntary contraction (QMVC), and endurance time (Tf) were measured. The multiple-parameter malnutrition index (MNI) was used for overall evaluation of the nutritional status of patients. The femoral muscle volume was estimated. All subjects were subjected to a routine pulmonary function test including indexes such as FEV1, FVC, FEV1/FVC (%), and PEF. Enzyme-linked immunoassay (ELISA) was used to measure the levels of myostatin, tumor necrosis factor-α, TNF-like apoptosis-inducing factor (TWEAK), surface active protein D (SPD), C-reactive protein (CRP), interleukin (IL)-1ß, and IL-6. The cell immunohistochemical method was used to detect the expression of nuclear factor Kappa B (NF-κB). RESULTS: There were significant differences in body weight, BMI, femoral muscle volume, and physical activity scores between the two groups (p<0.01). The MNI of patients in the COPD group was significantly higher than that in the control group (p<0.01). The QMVC of 51 male and 16 female patients decreased. All eight tested cytokines increased in the COPD group but there were only significant differences in four cytokines (p<0.05). CONCLUSIONS: Chronic systemic inflammation is a major risk factor of skeletal muscle dysfunction (SMD) in COPD patients. The levels of SPD, myostatin, TWEAK, and TNF-α decreased significantly in COPD patients.

[The clinical efficacy of coblation tonsillectomy and conventional tonsillectomy in China: A Meta analysis].

Objective:To systematically review the clinical efficacy of coblation tonsillectomy and conventional tonsillectomy in China. Method:Randomized controlled trials (RCT) of coblation tonsillectomy and conventional tonsillectomy were searched and retrieved through online databases (PubMed, Cumulative Index to Nursing and Allied Health, EMBASE, Cochrane Library, CBM, CNKI, VIP, WanFang, SUMsearch and Google search engine) and related literatures were reviewed up to 30 April, 2017. Two investigators independently screened literatures,extracted data and evaluated the risk of bias assessment tools for RCT using the Version 5.1.0 of Cochrane Handbook for Systematic Reviews of Interventions. Then, Meta analysis was performed using RevMan 5.3 software provided by the Cochrane Collaboration. Result:A total of 32 RCTs involving 3 197 tonsillectomy patients were included. The results of meta-analysis showed that: the operation time (MD=-17.03, 95%CI -19.78 to -14.28, P＜0.00 001), intraoperative blood loss (MD=-27.00, 95%CI -30.44 to -23.56, P＜0.00 001), postoperative pain in 24 hours (MD=-2.00, 95%CI -2.65 to -1.35, P＜0.00 001), time needed to regain the normal diet (MD=-2.01, 95%CI -2.60 to -1.42, P＜0.00001), formation time of white membrane (MD=-2.44, 95%CI -3.96 to -0.93, P=0.002) of patients in the coblation tonsillectomy group were all significantly lower than the conventional tonsillectomy group; while the exfoliation time of white membrane (MD=2.02, 95%CI 0.65 to 3.39, P=0.004) in the coblation tonsillectomy group was significantly longer than the conventional tonsillectomy group. Conclusion:Current evidence shows that, compared with the conventional tonsillectomy group, the coblation tonsillectomy group can significantly shorten the operation time, decrease intraoperative blood loss, alleviate postoperative pain degree during 24 hours, regain the normal diet early and form white membrane early, but delaye the exfoliation time of white membrane. Due to the limited kinds of literature and quality of the included studies, the above conclusions still need to be verified by carrying out more large scale samples and high quality randomized controlled trials (RCTs) studies.

[Effect of low-dose or standard-dose conjugated equine estrogen combined with different progesterone on bone density in menopause syndrome women].

Objective: To explore the effect of low-dose or standard-dose conjugated equine estrogen (CEE) combined with natural progesterone or dydrogesterone on bone density in menopause syndrome women. Methods: Totally 123 patients with menopause syndrome were recruited and randomly assigned to 3 treatment groups: group A (low-dose CEE+progesterone) , group B (standard-dose CEE+progesterone) , group C (standard-dose CEE+dydrogesterone) . Using continuous sequential regimen, the duration of intervention was 12 cycles. The bone mineral density of lumbar 2-4 and neck of femur, the bone metabolic markers, the level of FSH and estradiol were examined just before the drug administration and 12 months after the beginning of experiment. Results: There were 107 cases completed the one year trial. (1) Bone density: after 12 cycles of treatment, there was no significant change in bone density in group A (P>0.05) ; lumbar vertebrae of group B and C increased significantly, at 3.0% and 2.1%respectively (all P<0.05) . The bone density of left femoral neck of group C significantly increased by 2.9% (P=0.029) . There was no significant difference among the treatment groups at the beginning of experiment (P>0.05) . (2) Bone metabolic markers: after 12 cycles of treatment, the levels of calcium, phosphorus, alkaline phosphatase, Ca/Cr decreased significantly, the difference were statistically significant (all P<0.05) . There was no significant difference among the treatment groups at the beginning of experiment (P>0.05) . (3) Levels of FSH and estradiol: after 12 cycles of treatment, the levels of FSH in three groups were decreased significantly (all P<0.01) . The levels of estradiol in three groups were increased significantly (all P<0.01) . There was no significant difference among the treatment groups at the beginning of experiment (P>0.05) . Conclusions: Both low-dose and standard-dose menopause hormone therapy (MHT) could elevate the level of estradiol, reduce bone turnover, prevent bone loss of postmenopausal women effectively. The standard dose of MHT could also increase the density of vertebrae and femoral neck, and generate more clinical benefits.

[Current status and the consistency analysis of using two criteria for decision making of aspirin use for the primary prevention of ischemic cardiovascular disease in outpatients].

Objective: To compare the consistency and accuracy of using 2 criteria for decision making of aspirin use for the primary prevention of ischemic cardiovascular disease (ISCVD) and explore the current status and related factors of aspirin use for the primary prevention of ISCVD in Chinese outpatients. Methods: This cross-sectional study enrolled 3 018 outpatients with hypertension, diabetes, or hypercholesterolemia, who visited the General Practice (GP) clinics of Anzhen hospital in Beijing from September to December 2015 were enrolled in. The information of risk factors for ISCVD and use of aspirin was collected. Both quantitative and qualitative criteria were used to make the decision of aspirin use for primary prevention of ISCVD in this patient cohort. Quantitative criteria were derived from the 2011 Chinese guideline of cardiovascular disease prevention: aspirin use for primary cardiovascular disease prevention in population with risk of ISCVD in the next 10 years≥10%. Qualitative criteria were derived from the Chinese expert consensus on the aspirin use issued in 2013: aspirin should be given for the purpose of primary ISCVD in population with≥3 risk factors:(1) men aged ≥50 years or postmenopausal women; (2) hypertensive subjects with blood pressure ≤150/90 mmHg(1 mmHg=0.133 kPa);(3) diabetes; (4) hypocholesteremia; (5) obesity with body mass index (BMI)≥28 kg/m(2); (6) Smokers;(7) with familiar premature ISCVD history (male<55 years, female<65 years). Demographic data of participants were obtained by questionnaire, on-site measurements or screening previous medical records. Results: 67.1% participants (n=2 024) should be recommended to take aspirin as primary prevention medication using 10-year risk of ISCVD≥10% as the criteria, and 77.9% participants (n=2 350) should be recommended to take aspirin as primary prevention medication using number of risk factors≥3 as the criteria. With 10-year risk of ISCVD≥10% as the gold standard and risk factors≥3 as the evaluation criteria, the sensitivity was 97%, specificity was 61%, the consistency rate was 85%, Kappa value was 0.628 (U=35.824, P<0.001) , indicating that the consistency of the 2 criteria was good. The percentage of real-world aspirin use for primary prevention of ISCVD in this cohort was significantly higher for participants evaluated with the 10-year risk of ISCVD≥10% than that evaluated with 3 risk factors (53.1% vs. 49.2%, χ(2)=6.523, P=0.011). 12.7% participants with 10-year risk of ISCVD<10% and 6.6% participants with<3 risk factors took aspirin for the primary prevention of ISCVD in this cohort. Age, smoking, hypertension, diabetes and hypercholesterolemia were significantly related to the aspirin use in this cohort, relative ORs were 1.047 (95%CI 1.035-1.060) , 1.969 (95%CI 1.403-2.762) , 2.065 (95%CI 1.623-3.629) , 3.493 (95%CI 2.726-4.475, and 1.344 (95%CI 1.109-1.628) , respectively. Obesity and familial history of premature ISCVD were not related to the aspirin use, relative ORs were 1.137 (95%CI 0.828-1.562) and 0.986 (95%CI 0.767-1.266) . Conclusions: The consistency of the 2 criteria for decision making of aspirin use for the primary prevention of ISCVD is good and about 50% participants who should be recommended to the use of aspirin for the primary prevention of ISCVD took the aspirin in the real-world scenario. The use of aspirin as primary prevention strategy for ISCVD in the real-world scenario is related to age, smoking, hypertension, diabetes and hypercholesterolemia.

Influence of hormone therapy or C. foetida extract on breast tenderness in postmenopausal women.

OBJECTIVE: To evaluate the prevalence of breast tenderness in a population treated with menopausal hormone therapy (MHT) or Cimicifuga foetida extract. METHODS: A prospective, randomized, controlled trial was conducted. Ninety-six postmenopausal women were randomly assigned to three groups: group A, 1 mg estradiol valerate daily plus 4 mg medroxyprogesterone acetate (MPA), days 19-30; group B, 1 mg estradiol valerate daily plus 100 mg micronized progesterone (MP), days 19-30; group C, 100 mg C. foetida extract daily. Breast tenderness was evaluated daily for 12 months. RESULTS: Seventy-three patients completed the study. Group A had the highest prevalence of breast tenderness, while group C had the lowest. More than 50% of all participants reported no symptoms throughout the period. The participants in group A experienced a sharp increase in breast tenderness after treatment, but decreased after 1 month. No significant decline was found in the duration of pain in group B. The patients in group C reported no remarkable changes after 1 month. Compared to estrogen only, estrogen plus MPA/MP led to a higher incidence of prolonged breast symptoms. CONCLUSIONS: Compared to MHT groups, C. foetida extract had the lowest prevalence of breast tenderness. Most participants experienced mild or no symptoms.