Neuroimmune cardiovascular interfaces control atherosclerosis.

Atherosclerotic plaques develop in the inner intimal layer of arteries and can cause heart attacks and strokes1. As plaques lack innervation, the effects of neuronal control on atherosclerosis remain unclear. However, the immune system responds to plaques by forming leukocyte infiltrates in the outer connective tissue coat of arteries (the adventitia)2-6. Here, because the peripheral nervous system uses the adventitia as its principal conduit to reach distant targets7-9, we postulated that the peripheral nervous system may directly interact with diseased arteries. Unexpectedly, widespread neuroimmune cardiovascular interfaces (NICIs) arose in mouse and human atherosclerosis-diseased adventitia segments showed expanded axon networks, including growth cones at axon endings near immune cells and media smooth muscle cells. Mouse NICIs established a structural artery-brain circuit (ABC): abdominal adventitia nociceptive afferents10-14 entered the central nervous system through spinal cord T6-T13 dorsal root ganglia and were traced to higher brain regions, including the parabrachial and central amygdala neurons; and sympathetic efferent neurons projected from medullary and hypothalamic neurons to the adventitia through spinal intermediolateral neurons and both coeliac and sympathetic chain ganglia. Moreover, ABC peripheral nervous system components were activated: splenic sympathetic and coeliac vagus nerve activities increased in parallel to disease progression, whereas coeliac ganglionectomy led to the disintegration of adventitial NICIs, reduced disease progression and enhanced plaque stability. Thus, the peripheral nervous system uses NICIs to assemble a structural ABC, and therapeutic intervention in the ABC attenuates atherosclerosis.

Comparing transfusion reactions between pre-storage and post-storage leukoreduced apheresis platelets: an analysis using propensity score matching.

Transfusion reactions induced by platelet transfusions may be reduced and alleviated by leukocyte reduction of platelets. Although leukoreduction of apheresis platelets can be performed either pre-storage or post-storage, seldom studies directly compare the incidence of transfusion reaction in these two different blood products. We conducted a retrospective study to compare the transfusion reactions between pre-storage and post-storage leukoreduced apheresis platelets. We reviewed the general characteristics and the transfusion reactions, symptoms, and categories for inpatients who received pre-storage or post-storage leukoreduced apheresis platelets. Propensity-score matching was performed to adjust for baseline differences between groups. A total of 40,837 leukoreduction apheresis platelet orders were reviewed. 116 (0.53%) transfusion reactions were reported in 21,884 transfusions with pre-storage leukoreduction, and 174 (0.91%) reactions were reported in 18,953 transfusions with post-storage leukoreduction. Before propensity-score matching, the odds ratio for transfusion reactions in the pre-storage group relative to the post-storage group was 0.57 (95% confidence interval [CI] 0.45-0.72, P < 0.01); the odds ratio after matching was 0.63 (95% CI 0.49-0.80, P < 0.01). A two-proportion z-test revealed pre-storage leukoreduction significantly decreases the symptoms of chills, fever, itching, urticaria, dyspnea, and hypertension as compared with those in post-storage leukoreduction. Pre-storage leukoreduced apheresis platelet significantly decreased febrile non-hemolytic transfusion reaction as compared with post-storage groups. This study suggests pre-storage leukoreduction apheresis platelet significantly decreases the transfusion reaction as compared with those in post-storage leukoreduction.

Oral health self-management barriers among rural older adults in Guangxi, China: A qualitative study.

BACKGROUND: Objective: To understand the barriers associated with self-management of oral health among rural older adults in Guangxi, and to explore the high incidence of oral problems. This information will assist in the formulation of relevant strategies to solve the oral health problems in this population. METHODS: Taking a phenomenological approach, the current status of, and barriers to, oral health self-management in rural older adults from different regions of Guangxi were explored. Participants were purposively selected and interviewed face-to-face. RESULTS: The interviews yielded four overarching themes and six corresponding sub-themes pertaining to barriers in oral health self-management. These included: (1) Older adults' understanding of oral health and disease, perceptions of oral health and their oral health behaviours; (2) Problems in accessing oral health information; (3) Role of family support; and (4) Barriers to healthcare that included access to dental services, oral treatment experience and financial burden of access to dental care. CONCLUSION: Rural older adults in Guangxi face oral health self-management barriers. Improving access to oral healthcare services and changing existing oral health perceptions and habits may assist them in overcoming self-management challenges.

Associations of genetic markers of diabetes mellitus with carotid atherosclerosis: a community-based case-control study.

BACKGROUND: Diabetes mellitus (DM) is a well-established determinant of atherosclerosis and cardiovascular diseases (CVD). Recently, genome-wide association studies (GWAS) identified several single nucleotide polymorphism (SNP) significantly correlated with DM. The study aimed to explore the relationships of the top significant DM SNPs with carotid atherosclerosis (CA). METHODS: We used a case-control design and randomly selected 309 cases and 439 controls with and without, respectively, carotid plaque (CP) from a community-based cohort. Eight recent GWAS on DM in East Asians reported hundreds of SNPs with genome-wide significance. The study used the top significant DM SNPs, with a p-value < 10-16, as the candidate genetic markers of CA. The independent effects of these DM SNPs on CA were assessed by multivariable logistic regression analyses to control the effects of conventional cardio-metabolic risk factors. RESULTS: Multivariable analyses showed that, 9 SNPs, including rs4712524, rs1150777, rs10842993, rs2858980, rs9583907, rs1077476, rs7180016, rs4383154, and rs9937354, showed promising associations with the presence of carotid plaque (CP). Among them, rs9937354, rs10842993, rs7180016, and rs4383154 showed significantly independent effects. The means (SD) of the 9-locus genetic risk score (9-GRS) of CP-positive and -negative subjects were 9.19 (1.53) and 8.62 (1.63), respectively (p < 0.001). The corresponding values of 4-locus GRS (4-GRS) were 4.02 (0.81) and. 3.78 (0.92), respectively (p < 0.001). The multivariable-adjusted odds ratio of having CP for per 1.0 increase in 9-GRS and 4-GRS were 1.30 (95% CI 1.18-1.44; p = 4.7 × 10-7) and 1.47 (95% CI 1.74-9.40; p = 6.1 × 10-5), respectively. The means of multi-locus GRSs of DM patients were similar to those of CP-positive subjects and higher than those of CP-negative or DM-negative subjects. CONCLUSIONS: We identified 9 DM SNPs showing promising associations with CP. The multi-locus GRSs may be used as biomarkers for the identification and prediction of high-risks subjects for atherosclerosis and atherosclerotic diseases. Future studies on these specific SNPs and their associated genes may provide valuable information for the preventions of DM and atherosclerosis.

ABO Blood Group and Bleeding and Survival in VA-ECMO Patients.

ABO blood group has been shown to be a major determinant of plasma von Willebrand factor (vWF) levels. O blood group is associated with the lowest vWF levels and confers an increased risk of hemorrhagic events, while AB blood group has the highest levels and is associated with thromboembolic events. We hypothesized in extracorporeal membrane oxygenation (ECMO) patients that O blood type would have the highest and AB blood type would have the lowest transfusions, with an inverse relationship to survival. A retrospective analysis of 307 VA-ECMO patients at a major quaternary referral hospital was performed. The distribution of blood groups included 124 group O (40%), 122 group A (40%), 44 group B (14%), and 17 group AB (6%) patients. Regarding usage of packed red blood cells, fresh frozen plasma, and platelets, there was a non-statistically significant difference in transfusions, with group O having the least and group AB having the most requirements. However, there was a statistically significant difference in cryoprecipitate usage when comparing to group O: group A (1.77, 95% CI: 1.05-2.97, P < .05), group B (2.05, 95% CI: 1.16-3.63, P < .05), and group AB (3.43, 95% CI: 1.71-6.90, P < .001). Furthermore, a 20% increase in length of days on ECMO was associated with a 2-12% increase in blood product usage. The cumulative 30-day mortality rate for groups O and A was 60%, group B was 50%, and group AB was 40%; the 1-year mortality rate for groups O and A was 65%, group B was 57%, and group AB was 41%; however, the mortality differences were not statistically significant.

Red blood cell distribution width predicts mortality of adult patients receiving veno-arterial extracorporeal membrane oxygenation.

BACKGROUND: Red blood cell distribution width (RDW) is a numerical measure of the variation in the size of circulating red blood cells. Recently, there is increasing interest in the role of RDW as a biomarker for inflammatory states and as a prognostication tool for a wide range of clinical manifestations. The predictive power of RDW on mortality among patients receiving mechanical circulatory support remains largely unknown. METHODS: A retrospective analysis of 281 VA-ECMO patients at a tertiary referral academic hospital from 2009 to 2019 was performed. RDW was dichotomized with RDW-Low <14.5% and RDW-High ≥14.5%. The primary outcome was all-cause mortality at 30 days and 1 year. Cox proportional hazards models were used to examine the association between RDW and the clinical outcomes after adjusting for additional confounders. RESULTS: 281 patients were included in the analysis. There were 121 patients (43%) in the RDW-Low group and 160 patients (57%) in the RDW-High group. Survival to ECMO decannulation [RDW-H: 58% versus RDW-L: 67%, p = 0.07] were similar between the two groups. Patients in RDW-H group had higher 30-days mortality (RDW-H: 67.5% vs RDW-L: 39.7%, p < 0.001) and 1 year mortality (RDW-H: 79.4% vs RDW-L: 52.9%, p < 0.001) compared to patients in the RDW-L group. After adjusting for confounders, Cox proportional hazards model demonstrated that patients with high RDW had increased odds of mortality at 30 days (hazard ratio 1.9, 95% CI 1.2-3.0, p < 0.01) and 1 year (hazard ratio 1.9, 95% CI 1.3-2.8, p < 0.01) compared to patients with low RDW. CONCLUSIONS: Among patients receiving mechanical circulatory support with VA-ECMO, a higher RDW was independently associated with increased 30-days and 1-year mortality. RDW may serve as a simple biomarker that can be quickly obtained to help provide risk stratification and predict survival for patients receiving VA-ECMO.

Impact of prolonged use of adjuvant tocolytics after cervical cerclage on late abortion and premature delivery.

We evaluated the impact of cervical cerclage combined with one or more uterine contraction inhibitors in persistent inhibition of uterine contraction for the treatment of late abortion and premature delivery. This retrospective case series study analysed the medical data of 58 patients who underwent cervical cerclage for cervical insufficiency and simultaneously received one or more uterine contraction inhibitors (indomethacin, ritodrine, and atosiban) and magnesium sulphate at the Zibo Maternal and Child Health Hospital between January 2019 and December 2020.Patients are normal pregnancy who received cervical cerclage without complications. The rate of successful treatment was 74.14% (43/58). The prolonged gestation duration was 16.42 ± 7.84 weeks, and the average delivery gestational age was 35.91 ± 5.16 weeks. The longest duration of treatment with a uterine contraction inhibitor or inhibitors in combination or with magnesium sulphate alone was 15.34 ± 13.16 days, and nine cases developed adverse reactions. Persistent uterine contraction inhibition after cervical cerclage could prolong pregnancy and improve pregnancy outcomes.Impact statementWhat is already known on this subject? A crucial reason for treatment failure of cervical cerclage is that uterine contraction was not effectively inhibited.What do the results of this study add? Persistent inhibition of uterine contraction after cervical cerclage prolonged pregnancy duration, increased gestational age at delivery, and improved pregnancy outcomes.What are the implications of these findings for clinical practice and/or further research? This study may provide a clinical basis for prolonging gestational age, preventing late abortion and premature delivery, and improving the survival rate and quality of life of premature infants.

Comparison of four screening methods for sarcopenia among community-dwelling older adults: A diagnostic accuracy study.

This study aimed to compare the diagnostic values of SARC-F (strength, assistance with walking, rising from a chair, climbing stairs, and falls), SARC-Calf (SARC-F combined with calf circumference), CC (calf circumference), and the Yubi-wakka (finger-ring) test for screening for sarcopenia in community-dwelling older adults. The Asian Working Group for Sarcopenia (AWGS) 2019 criteria were used as a standard reference. A total of 209 participants were enrolled, and 40.7% were identified as sarcopenia. The sensitivity, specificity, and AUC were respectively 54.1%, 70.2%, and 0.687 for SARC-F; 76.5%, 73.4% and 0.832 for SARC-calf, 86.7%, 82.4%, and 0.906 for CC in men, and 85.5%, 63.3%, and 0.877 for CC in women. Relative to the "bigger," a significant association between sarcopenia and the Yubi-wakka test ("just fits" OR: 4.1, 95% CI: 1.57-10.98; "small" OR: 27.5, 95% CI: 10.14-74.55) was observed. The overall accuracy of CC was better than SARC-Calf for sarcopenia screening.

[Distribution of memory B cell subsets in peripheral blood of children with frequently relapsing nephrotic syndrome]. / é¢‘å¤å‘è‚¾ç— ç»¼åˆå¾æ‚£å„¿å¤–å‘¨è¡€è®°å¿†B细胞亚群分布变化.

OBJECTIVES: To investigate the change in the distribution of memory B cell subsets in children with frequently relapsing nephrotic syndrome (FRNS) during the course of the disease. METHODS: A total of 35 children with primary nephrotic syndrome (PNS) who attended the Department of Pediatrics of the Affiliated Hospital of Xuzhou Medical University from October 2020 to October 2021 were enrolled as subjects in this prospective study. According to the response to glucocorticoid (GC) therapy and frequency of recurrence, the children were divided into two groups: FRNS (n=20) and non-FRNS (NFRNS; n=15). Fifteen children who underwent physical examination were enrolled as the control group. The change in memory B cells after GC therapy was compared between groups, and its correlation with clinical indicators was analyzed. RESULTS: Before treatment, the FRNS and NFRNS groups had significantly increased percentages of total B cells, total memory B cells, IgD+ memory B cells, and IgE+ memory B cells compared with the control group, and the FRNS group had significantly greater increases than the NFRNS group (P<0.05); the FRNS group had a significantly lower percentage of class-switched memory B cells than the NFRNS and control groups (P<0.05). After treatment, the FRNS and NFRNS groups had significant reductions in the percentages of total B cells, total memory B cells, IgM+IgD+ memory B cells, IgM+ memory B cells, IgE+ memory B cells, IgD+ memory B cells, and IgG+ memory B cells (P<0.05) and a significant increase in the percentage of class-switched memory B cells (P<0.05). The FRNS group had a significantly higher urinary protein quantification than the NFRNS and control groups (P<0.05) and a significantly lower level of albumin than the control group (P<0.05). In the FRNS group, urinary protein quantification was negatively correlated with the percentage of class-switched memory B cells and was positively correlated with the percentage of IgE+ memory B cells (P<0.05). CONCLUSIONS: Abnormal distribution of memory B cell subsets may be observed in children with FRNS, and the percentages of IgE+ memory B cells and class-switched memory B cells can be used as positive and negative correlation factors for predicting recurrence after GC therapy in these children.

Nuclear respiratory factor 1 promotes the growth of liver hepatocellular carcinoma cells via E2F1 transcriptional activation.

BACKGROUND: Recent studies have shown that functional mitochondria are essential for cancer cells. Nuclear respiratory factor 1 (NRF1) is a transcription factor that activates mitochondrial biogenesis and the expression of the respiratory chain, but little is known about its role and underlying mechanism in liver hepatocellular carcinoma (LIHC). METHODS: NRF1 expression was analyzed via public databases and 24 paired LIHC samples. Clinical-pathological information and follow-up data were collected from 165 patients with LIHC or online datasets. Furthermore, cellular proliferation and the cell cycle were analyzed by MTT, Clone-forming assay and flow cytometric analyses. NRF1 target genes were analyzed by Chromatin immunoprecipitation sequencing (ChIP-Seq). PCR and WB analysis was performed to detect the expression of related genes. ChIP and luciferase activity assays were used to identify NRF1 binding sites. RESULTS: Our results showed that NRF1 expression was upregulated in LIHC compared to normal tissues. NRF1 expression was associated with tumour size and poor prognosis in patients. Knockdown of NRF1 repressed cell proliferation and overexpression of NRF1 accelerated the G1/S phase transition. Additionally, data from ChIP-seq pointed out that some NRF1 target genes are involved in the cell cycle. Our findings indicated that NRF1 directly binds to the E2F1 promoter as a transcription factor and regulates its gene expression. CONCLUSION: Therefore, this study revealed that NRF1 promotes cancer cell growth via the indirect transcriptional activation of E2F1 and is a potential biomarker in LIHC.

Association Between Body Mass Index and Outcomes in Venoarterial Extracorporeal Membrane Oxygenation.

BACKGROUND: The association between obesity, or elevated body mass index (BMI), and outcomes in patients receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO) has not been well established. Recent studies in patients receiving venovenous ECMO did not detect an association between obesity and increased mortality. The purpose of this retrospective observational study is to evaluate the association between BMI and survival in patients receiving VA-ECMO for cardiogenic shock. METHODS: All patients >18 years of age supported on VA-ECMO for refractory cardiogenic shock in a single academic center between 2009 and 2019 were included. ECMO outcomes, including successful ECMO decannulation and 30-day survival, were analyzed after stratification according to BMI. Multivariable and univariate logistic regression were used to assess the association between BMI and VA-ECMO outcomes. RESULTS: Of the total patients (n = 355) cannulated for VA-ECMO, 61.7% of the patients survived to ECMO recovery/decannulation, 45.5% of the patients survived to 30 days after ECMO decannulation, and 38.9% of the patients survived to hospital discharge with no statistically significant differences among the BMI groups. Multivariable logistic regression did not reveal any associations between obesity as defined by BMI and survival to ECMO decannulation (odds ratio [OR] 1.07 per 5 unit increase in BMI, 95% confidence interval [CI], 0.86-1.33; P = .57), 30-day survival (OR = 0.91, 95% CI, 0.73-1.14; P = .41) or survival to hospital discharge (OR = 0.95, 95% CI, 0.75-1.20; P = .66). CONCLUSIONS: Despite potential challenges to cannulation and maintaining adequate flow during ECMO, this single centered, retrospective observational study did not detect association between BMI and survival to ECMO decannulation, 30-day survival, or survival to hospital discharge for patients requiring VA-ECMO for refractory cardiogenic shock. These data suggest that obesity alone should not exclude candidacy for VA-ECMO.The primary outcome in this retrospective study was survival of the ECMO therapy (survival to ECMO decannulation), defined as surviving >24 hours after decannulation without a withdrawal of care. Secondary outcomes included survival at 30 days and survival to hospital discharge.

Prevalences of diabetes mellitus and carotid atherosclerosis and their relationships in middle-aged adults and elders: a community-based study.

BACKGROUND/PURPOSE: Atherosclerosis and diabetes mellitus (DM) are both severe chronic diseases that cause huge burdens on patients' families and societies. Connections between the two diseases have brought high attention recently, however, population-based study with large sample size was few. The study aimed to explore the relationship between carotid atherosclerosis and DM. METHODS: We enrolled 3908 adults aged 40-74 years from communities and measured their cardio-metabolic profiles and scanned their carotid arteries bilaterally. RESULTS: The overall prevalence rates of carotid plaque and DM were 34.4 and 10.7%, respectively. The age-specific prevalence rates of DM and carotid plaque were nearly linearly correlated in both sexes (both Pearson's correlation coefficient r > 0.97). The prevalence rates of carotid plaque, total plaque number ≥3, maximum diameter stenosis ≥30%, and plaque score ≥3 were 53.6, 24.8, 19.1, and 28.6%, respectively, in DM patients and were 32.1, 9.4, 9.8, and 11.2%, respectively, in non-DM controls. After adjustment for other conventional risk factors, the multivariable-adjusted OR of having carotid plaque was 1.60 (95% CI 1.27-2.01) and were 2.06 (95% CI 1.55-2.75), 1.33 (95% CI 0.99-1.78), and 2.03 (95% CI 1.55-2.65) for total plaque number ≥3, maximum diameter stenosis ≥30%, and plaque score ≥3, respectively. CONCLUSION: We demonstrated that prevalences of DM were linearly correlated with prevalences of carotid plaque and DM patients had higher prevalence rates of carotid plaque and more advanced carotid atherosclerosis than non-DM controls. Our results indicated the need to address the role of DM in atherosclerosis development.

Prevalence and prognosis of hard-to-heal wounds with comorbidities in China.

OBJECTIVE: Regular retrospective analysis is necessary for potential improvement in clinical practice for the treatment of hard-to-heal wounds. Comorbidities and outcomes have demonstrated spatial and temporal diversity, emphasising the importance of updates in epidemiology. The complexity of healing hard-to-heal wounds has long been known, and so we sought evidence-based improvement on the current principles of treatment. METHOD: Demographic and clinical information of patients from the WoundCareLog database was collected. Patients who met the inclusion criteria and completed follow-up after treatment were included. Comorbidities were diagnosed and classified into eight categories based on ICD-10. We compared the demographic and aetiological characteristics between patients with and without comorbidities by t-test and Chi-squared test. The impact of comorbidities on wound healing were evaluated with a multivariate Cox model. RESULTS: A total of 2163 patients met the inclusion criteria and were enrolled, of whom 37.0% were aged 61-80 years, 36.0% were aged 41-60 years and 60.8% were male. The lower extremities and buttocks were the most commonly affected areas with hard-to-heal wounds. Non-traumatic wounds accounted for 66.6% of cases, and infection, pressure and diabetes were the most common causes. Paralysis and diabetes were the most important factors which led to a prolonged healing process and inferior clinical outcomes. CONCLUSION: Comorbidities of hard-to-heal wounds were treated as separate contributors and their weighted effect on outcome was calculated through correlation analysis. Paralysis and diabetes were the most unfavourable comorbidities affecting the treatment of non-traumatic hard-to-heal wounds. Our study highlighted the priority of comorbidity treatment through data-driven approaches. It provides potential value in developing better public health strategies and preventive medicine.

Association of Common Variants in OLA1 Gene with Preclinical Atherosclerosis.

Reactive oxygen species impair the blood vessels, leading to the initiation of atherosclerosis, and migration and proliferation of vascular smooth muscle cells and neovascularization by endothelial cells of vasa vasorum are essential for atherosclerosis development. Obg-like ATPase 1 (OLA1), a negative regulator in cellular responses to oxidative stress, binds to breast cancer susceptibility gene 1 (BRCA1), which protects vascular endothelial and smooth muscle cells against reactive oxygen species. However, it is not known whether OLA1 is genetically correlated with atherosclerosis. Here, we conducted two independent population-based case-control studies to explore the effects of variants in OLA1 genes on preclinical atherosclerosis. A total of 564 and 746 subjects who had thicker and normal carotid intima-media thickness (cIMT), respectively, were enrolled. Among 55 screened SNPs, rs35145102, rs201641962, rs12466587, rs4131583, and rs16862482 in OLA1 showed significant associations with cIMT. SNP rs35145102 is a 3'-utr variant and correlates with the differential expression of OLA1 in immune cells. These five genetic markers form a single closely linked block and H1-ATTGT and H2-GCCTC were the top two most prevalent 5-locus haplotypes. The H1 + H1 genotype negatively and H1 + H2 genotype positively correlated with thicker cIMT. The five identified SNPs in the OLA1 gene showed significant correlations with cIMT. Furthermore, we found that OLA1 was required for migration and proliferation of human aortic endothelial and smooth muscle cells and regulated vascular tube formation by human aortic endothelial cells. Therefore, these genetic variants in the OLA1 gene may serve as markers for risk prediction of atherosclerotic diseases.

[The Impact of Critical Care Transition Programs (CCTPs) on Relocation Stress in Patients and Patient Families in the Intensive Care Unit].

The intensive care unit (ICU) is designed to care for patients with high disease severity who require critical care and close monitoring. Patients in the ICU may be transferred to the general ward for further treatment following recovery from the acute phase. Transferring from the ICU to the general ward after acute phase recovery is a stressful event that may stress both the patient and their family, potentially resulting in relocation stress syndrome (RSS). RSS has been found to be closely related to unplanned ICU readmissions, prolonged hospitalization, and adverse events, affecting recovery to health and family peace of mind. Furthermore, RSS may result in ineffective disease coping, feelings of uncertainty, and poor treatment response, leading to prolonged hospitalization, reduced trust in medical staff, and decreased happiness and quality of life. In recent years, the nursing profession has attached increasing importance to holistic health care. This has encouraged critical care teams to map out customized relocation plans for patients who are about to be transferred from the ICU that use standardized evaluation tools for transfers and elicit the situation and needs from patients or their family. Through the setting of care goals, shared decision making, and cross-unit support, enhanced communications among the medical team facilitate transition preparation and improve the quality and effect of intensive care.

Singlet Biradical Versus Triplet Biradical/Zwitterion Characteristics in Isomers of C6 -C5 -C6 -C7 -C6 -Fused Pentacyclic Aromatic Hydrocarbons Revealed through Reactivity Patterns.

Among various polycyclic aromatic hydrocarbons, C6 -C5 -C6 -C7 -C6 fused pentacyclic aromatic hydrocarbons have the unique potential to adopt quinonoid, zwitterion, singlet, or triplet biradical electronic configurations. Two such hybrid structures between pentacene and azulene were synthesized and their ground state electronic configurations were deduced from the reactivity patterns they exhibit respectively. Compound 6, where the radicaloid carbons are linked through a para-phenylene, forms a head-to-head dimer like a singlet biradical. In contrast, isomer 7, where the para-linkage was switched to meta, reacts readily with oxygen which resembles the reactivity of a triplet state. The oxidized intermediate(s) then undergoes rearrangement to furnish the C6 -C5 -C6 -C6 -C6 ring contraction product 13. Cation 14, the protonated form of 7, was synthesized, which implies 7 also reacts like a zwitterion. It was revealed the oxidative rearrangement takes place even with mesityl dibenzotropylium cation despite its perceived aromaticity. DFT calculations confirm the most stable forms of 6 and 7 are singlet and triplet diradical, which is consistent with the observed reactivity of respective molecules.

Silver-Mediated [3 + 2] Cycloaddition of Azomethine Ylides with Trifluoroacetimidoyl Chlorides for the Synthesis of 5-(Trifluoromethyl)imidazoles.

A silver-mediated [3 + 2] cycloaddition of azomethine ylides with trifluoroacetimidoyl chlorides for the rapid assembly of 5-(trifluoromethyl)imidazoles has been developed. Notable features of the reaction include readily accessible reagents, a broad substrate scope, and high efficiency. The protocol can be successfully applied to construct the analogue of the specific allosteric modulator of GABAA receptors. The silver species could be recycled by a simple operation.

An N-heterocyclic carbene-catalyzed switchable reaction of 9-(trimethylsilyl)fluorene and aldehydes: chemoselective synthesis of dibenzofulvenes and fluorenyl alcohols.

An N-heterocyclic carbene-catalyzed synthesis of dibenzofulvenes and fluorenyl alcohols was developed. In the presence of 10 mol% NHC (1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) and 4 Å molecular sieves, 9-(trimethylsilyl)fluorene undergoes an olefination reaction with aldehydes to produce dibenzofulvenes in 43-99% yields. However, on reducing the NHC loading to 1 mol% and with the addition of water, 9-(trimethylsilyl)fluorene selectively undergoes nucleophilic addition with aldehydes to afford fluorenyl alcohols in 40-95% yields.

Overlapping Drug-Eluting Stent Is Associated with Increased Definite Stent Thrombosis and Revascularization: Results from 15,561 Patients in the AUTHENTIC Study.

PURPOSE: This study was to analyze the incidence of definite stent thrombosis (ST) after the implantation of drug-eluting stents (DESs) and cutoff value of overlapping length for predicting definite ST. An overlapping stent is associated with a high rate of clinical events after DES implantation compared with a non-overlapping stent. However, the rates of definite ST and clinical outcomes from a large patient population remain underreported. METHODS: A total of 15,561 patients with 24,183 lesions who underwent DES implantation from January 2005 to February 2017 were retrospectively included in 5 tertiary hospitals in China. The main endpoint was the incidence of definite ST after procedures. RESULTS: With a median of 1932 (IQR = 1194-2929) days, clinical follow-up was available in 7484 patients in the overlap group and in 8077 patients in the non-overlap group. The rates of definite ST were 3.1% in the overlap group and 1.2% in the non-overlap group (HR: 2.67 (95% CI: 2.11-3.38), p < 0.001). Of the 24,183 treated lesions, the incidences of definite ST were 2.4% in the overlap group and 0.9% in the non-overlap group (HR: 2.96 (95% CI: 2.38-3.69), p < 0.001). Stent overlap was associated with a higher rate of target lesion revascularization (TLR) (9.4%) compared with stent non-overlap (6.4%, p < 0.001). The length of overlapping stent ≥ 2.93 mm strongly correlated with definite ST. CONCLUSION: The present study shows that overlapping DES increases definite ST and revascularization in patients during long-term follow-up. In addition, the longer overlapping zone was associated with worse clinical outcomes.

Curcumin Affects Leptin-Induced Expression of Methionine Adenosyltransferase 2A in Hepatic Stellate Cells by Inhibition of JNK Signaling.

INTRODUCTION: Obese patients are often accompanied by hyperleptinemia and prone to develop liver fibrosis. Accumulating data including those obtained from human studies suggested the promotion role of leptin in liver fibrosis. The remodeling of the DNA methylation is an epigenetic mechanism for regulating gene expression and is essential for hepatic stellate cell (HSC) activation, a key step in liver fibrogenesis. Leptin increases the expression of methionine adenosyltransferase 2A (MAT2A) which is associated with DNA methylation and HSC activation. Curcumin, an active polyphenol of the golden spice turmeric, inhibits leptin-induced HSC activation and liver fibrogenesis. Thus, the present research aimed to investigate the influence of curcumin on the roles of leptin in MAT2A expression in HSCs. METHODS: The in vivo experiments were conducted by using leptin-deficient obese mice. The gene expressions were examined by Western blot, real-time PCR, promoter activity assay, and immunostaining analysis. RESULTS: Curcumin reduced leptin-induced MAT2A expression. JNK signaling contributed to leptin-induced increase in MAT2A level, which could be interrupted by curcumin treatment. Curcumin inhibited leptin-induced MAT2A promoter activity by influencing MAT2A promoter fragments between -2,847 bp and - 2,752 bp and between -2,752 bp and +49 bp. The effect of curcumin on leptin-induced MAT2A expression paralleled the reductions in leptin-induced activated HSCs and liver fibrosis. CONCLUSION: These results might have implications for curcumin inhibition of the liver fibrogenesis in obese patients with hyperleptinemia.