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The development of new chemically recyclable polymers via monomer design would provide a transformative strategy to address the energy crisis and plastic pollution problem. Biaryl-fused cyclic esters were targeted to generate axially chiral polymers, which would impart new material performance. To overcome the non-polymerizability of the biaryl-fused monomer DBO, a cyclic ester Me-DBO installed with dimethyl substitution was prepared to enable its polymerizability via enhancing torsional strain. Impressively, Me-DBO readily went through well-controlled ring-opening polymerization, producing polymer P(Me-DBO) with high glass transition temperature (Tg >100 °C). Intriguingly, mixing these complementary enantiopure polymers containing axial chirality promoted a transformation from amorphous to crystalline material, affording a semicrystalline stereocomplex with a melting transition temperature more than 300 °C. P(Me-DBO) were capable of depolymerizing back to Me-DBO in high efficiency, highlighting an excellent recyclability.
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BACKGROUND: Ischemia preconditioning (IPC) ameliorates coronary no-reflow induced by ischemia/reperfusion (I/R) injury, and pericytes play an important role in microvascular function. However, it is unclear whether IPC exerts a protective effect on coronary microcirculation and regulates the pericytes. OBJECTIVE: The purpose of this study was to assess whether IPC improves coronary microvascular perfusion and reduces pericyte constriction after myocardial I/R injury. METHODS: Rats were randomly divided into three groups: the sham group, the I/R group, and the IPC + I/R group. The left anterior descending artery (LAD) of rats in the I/R group were ligated for 45 min, and the rats in the IPC + I/R group received 4 episodes of 6min occlusion followed by 6min reperfusion before the LAD was ligated. After 24 h of reperfusion, the area of no-reflow, and area at risk were evaluated with thioflavin-S and Evens blue staining, and infarct size with triphenyl tetrazolium chloride staining, respectively. Besides, fluorescent microspheres were perfused to enable visualization of the non-obstructed coronary vessels. Cardiac pericytes and microvascular were observed by immunofluorescence, and the diameter of microvascular at the site of the pericyte somata was analyzed. RESULTS: The infarct size, and area of no-reflow in the IPC + I/R group were significantly reduced compared with the I/R group (infarct size, 33.5% ± 11.9% vs. 49.2% ± 9.4%, p = 0.021ï¼no-reflow, 12.7% ± 5.2% vs. 26.6% ± 5.0%, p < 0.001). IPC improved microvascular perfusion and reduced the percentage of the blocked coronary capillary. Moreover, we found that cardiac pericytes were widely distributed around the microvascular in various regions of the heart, and expressed the contractile protein α-smooth muscle actin. The microvascular lumen diameter at pericyte somata was reduced after I/R (4.3 ± 1.0 µm vs. 6.5 ± 1.2 µm, p < 0.001), which was relieved in IPC + I/R group compared with the I/R group (5.2 ± 1.0 µm vs. 4.3 ± 1.0 µm, p < 0.001). Besides, IPC could reduce the proportion of apoptotic pericytes compared to the I/R group (22.1% ± 8.4% vs. 38.5% ± 7.5%, p < 0.001). CONCLUSION: IPC reduced no-reflow and inhibited the contraction of microvascular pericytes induced by cardiac I/R injury, suggesting that IPC might play a protective role by regulating the pericyte function.
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Infarto do Miocárdio , Traumatismo por Reperfusão Miocárdica , Animais , Vasos Coronários , Isquemia , Traumatismo por Reperfusão Miocárdica/metabolismo , Pericitos/metabolismo , RatosRESUMO
OBJECTIVE: We aimed to investigate the association between triglyceride glucose index and cardiovascular disease (CVD) development in the Chinese middle-aged and elderly population using the China Health and Retirement Longitudinal Study dataset 2011-2018. METHODS: Basic characteristics of participants, including sociodemographic information, and health conditions, were acquired. Logistic regression analyses and restricted cubic spline regression analyses were conducted to investigate the association between the triglyceride glucose index and future CVD risks. Subgroup analyses were performed to evaluate potential interaction. RESULTS: Seven hundred fifty-three of 6114 (12.3%) participants have developed CVD in 2018 over an approximately 7-year follow-up. The logistic regression analysis exhibited that compared to the lowest triglyceride glucose index group, the multivariable OR for future CVD was 0.985 (95%CI 0.811-1.198) in the T2 triglyceride glucose index group and 1.288 (95%CI 1.068-1.555) in the T3 TyG index (P for trend 0.006). The restricted cubic spline regression analysis showed the nonlinear association between triglyceride glucose index and CVD incidence; the cut-off values were 8.07 and 8.57, respectively, after total adjustment. Gender, fast blood glucose, and triglycerides interacted with triglyceride glucose index and CVD except for BMI. CONCLUSION: The triglyceride glucose index was nonlinearly related to the risk of future cardiovascular disease in the middle-aged and elderly Chinese population.
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Doenças Cardiovasculares , Adulto , Idoso , Biomarcadores , Glicemia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , China/epidemiologia , Glucose , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , TriglicerídeosRESUMO
OBJECTIVE: We aimed to investigate the effect of the triglyceride glucose (TyG) index on the association between diabetes and cardiovascular disease (CVD). METHODS: Data from 6,114 individuals were extracted and analyzed from the China Health and Retirement Longitudinal Survey (CHARLS) from 2011 to 2018. Logistic regression analyses were conducted to assess the relationship between diabetes and CVD across the various TyG index groups. The statistical method of subgroup analysis was used to determine the correlation between diabetes and CVD for each TyG index group by sex, history of hypertension and dyslipidemia, smoking, and drinking. RESULTS: Diabetes was positively associated with CVD risk after adjustment in 2011(odds ratio (OR) 1.475, 95% CI 1.243-1.752, P < 0.001). There was a gradient increase in the OR for new-onset CVD in 2018 due to diabetes at baseline across the value of the TyG index based on a fully adjusted model (P for trend < 0.05). The ORs of diabetes at baseline for CVD in 2018 were 1.657 (95% CI 0.928-2.983, P = 0.098), 1.834(95% CI 1.064-3.188, P = 0.037) and 2.234(95% CI 1.349-3.673, P = 0.006) for T1, T2 and T3 of the TyG index respectively. The gradient of increasing risk of CVD still existed among those with hypertension and nondrinkers in the subgroup analysis. CONCLUSION: Elevated TyG index strengthens the correlation between diabetes mellitus and CVD in middle-aged and elderly Chinese adults.
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Doenças Cardiovasculares , Diabetes Mellitus , Hipertensão , Adulto , Idoso , Biomarcadores , Glicemia/análise , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , China/epidemiologia , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Glucose , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Estudos Longitudinais , Pessoa de Meia-Idade , Aposentadoria , Medição de Risco/métodos , Fatores de Risco , TriglicerídeosRESUMO
The development of innovative synthetic polymer systems to overcome the trade-offs between the polymer's depolymerizability and performance properties is in high demand for advanced material applications and sustainable development. In this contribution, we prepared a class of aromatic cyclic esters (M1-M5) from thiosalicylic acid and epoxides by facile one-pot synthesis. Ring-opening polymerization of Ms afforded aromatic polyesters P(M)s with high molecular weights and narrow dispersities. The physical and mechanical properties of P(M)s can be modulated by stereocomplexation and regulation of the side-chain flexibility of the polymers, ultimately achieving high-performance properties such as high thermal stability and crystallinity (Tm up to 209 °C), as well as polyolefin-like high mechanical strength, ductility, and toughness. Furthermore, the functionalizable moieties of P(M)s have driven a wide array of post-polymerization modifications toward access to value-added materials. More importantly, the P(M)s were able to selectively depolymerize into monomers in excellent yields, thus establishing its circular life cycle.
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The development of high-performance recyclable polymers represents a circular plastics economy to address the urgent issues of plastic sustainability. Herein, we design a series of biobased seven-membered-ring esters containing aromatic and aliphatic moieties. Ring-opening polymerization studies showed that they readily polymerize with excellent activity (TOF up to 2.1 × 105 h-1) at room temperature and produce polymers with high molecular weight (Mn up to 438 kg/mol). The variety of functionalities allows us to investigate the substitution effect on polymerizability/recyclability of monomers and properties of polymers (such as Tgs from -1 to 79 °C). Remarkably, a stereocomplexed P(M2) exhibited significantly increased Tm and crystallization rate. More importantly, product P(M)s were capable of depolymerizing into their monomers in solution or bulk with high efficiency, thus establishing their circular life cycle.
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PURPOSE: Advancing age is the major risk factor for thoracic aortic aneurysm/dissection (TAAD). However, the causative link between age-related molecules and TAAD remains elusive. Here, we investigated the role of Sirtuin 1 (SIRT1, also known as class III histone deacetylase), the best studied member of the longevity-related Sirtuin family, in TAAD development in vivo. METHODS: We used male smooth muscle-specific SIRT1 transgenic (ST-Tg) mice, smooth muscle-specific SIRT1 knockout (ST-KO) mice, and their wild-type (WT) littermates on a C57BL/6J background to establish a TAAD model induced by oral administration of 3-aminopropionitrile fumarate (BAPN). We analyzed the incidence and fatality rates of TAAD in the groups. We examined matrix metallopeptidase 2 (MMP2) and MMP9 expression in aortas or cultured A7r5 cells via western blotting and real-time polymerase chain reaction (PCR). We performed chromatin immunoprecipitation (ChIP) to clarify the epigenetic mechanism of SIRT1-regulated MMP2 expression in vascular smooth muscle cells (VSMCs). RESULTS: BAPN treatment markedly increased the incidence of TAAD in WT mice but caused less disease in ST-Tg mice. Moreover, ST-KO mice had the highest BAPN-induced TAAD fatality rate of all the groups. Mechanistically, SIRT1 overexpression resulted in lower MMP2 and MMP9 expression after BAPN treatment in both mouse aortas and cultured A7r5 cells. The downregulation of BAPN-induced MMP2 expression by SIRT1 was mediated by deacetylation of histone H3 lysine 9 (H3K9) on the Mmp2 promoter in the A7r5 cells. CONCLUSION: Our findings suggest that SIRT1 expression in SMCs protects against TAAD and could be a novel therapeutic target for TAAD management.
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Aneurisma da Aorta Torácica/prevenção & controle , Dissecção Aórtica/prevenção & controle , Músculo Liso Vascular/enzimologia , Miócitos de Músculo Liso/enzimologia , Sirtuína 1/metabolismo , Acetilação , Dissecção Aórtica/enzimologia , Dissecção Aórtica/genética , Dissecção Aórtica/patologia , Animais , Aorta Torácica/enzimologia , Aorta Torácica/patologia , Aneurisma da Aorta Torácica/enzimologia , Aneurisma da Aorta Torácica/genética , Aneurisma da Aorta Torácica/patologia , Linhagem Celular , Modelos Animais de Doenças , Histonas/metabolismo , Masculino , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/patologia , Transdução de Sinais , Sirtuína 1/genéticaRESUMO
Background: Naringenin, a member of the dihydroflavone family, has been shown to have a protective function in multiple diseases. We previously demonstrated that naringenin played a protective role in hypertensive myocardial hypertrophy by decreasing angiotensin-converting enzyme (ACE) expression. The kidney is a primary target organ of hypertension. The present study tested the effect of naringenin on renovascular hypertensive kidney damage and explored the underlying mechanism. Methods and Results: An animal model of renovascular hypertension was established by performing 2-kidney, 1-clip (2K1C) surgery in Sprague Dawley rats. Naringenin (200 mg/kg/day) or vehicle was administered for 10 weeks. Blood pressure and urinary protein were continuously monitored. Plasma parameters, renal pathology and gene expression of nonclipped kidneys were evaluated by enzyme-linked immunosorbent assay, histology, immunohistochemistry, real-time polymerase chain reaction, and Western blot at the end of the study. Rats that underwent 2K1C surgery exhibited marked elevations of blood pressure and plasma Ang II levels and renal damage, including mesangial expansion, interstitial fibrosis, and arteriolar thickening in the nonclipped kidneys. Naringenin significantly ameliorated hypertensive nephropathy and retarded the rise of Ang II levels in peripheral blood but had no effect on blood pressure. 2K1C rats exhibited increases in the ACE/ACE2 protein ratio and AT1R/AT2R protein ratio in the nonclipped kidney compared with sham rats, and these increases were significantly suppressed by naringenin treatment. Conclusions: Naringenin attenuated renal damage in a rat model of renovascular hypertension by normalizing the imbalance of renin-angiotensin system activation. Our results suggest a potential treatment strategy for hypertensive nephropathy.
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Flavanonas/farmacologia , Hipertensão Renovascular/tratamento farmacológico , Rim/patologia , Sistema Renina-Angiotensina/efeitos dos fármacos , Administração Oral , Animais , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Flavanonas/uso terapêutico , Humanos , Hipertensão Renovascular/etiologia , Hipertensão Renovascular/patologia , Rim/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-Dawley , Resultado do TratamentoRESUMO
The development of chemically recyclable polymers serves as an attractive approach to address the global plastic pollution crisis. Monomer design principle is the key to achieving chemical recycling to monomer. Herein, we provide a systematic investigation to evaluate a range of substitution effects and structure-property relationships in the É-caprolactone (CL) system. Thermodynamic and recyclability studies reveal that the substituent size and position could regulate their ceiling temperatures (Tc). Impressively, M4 equipped with a tert-butyl group displays a Tc of 241 °C. A series of spirocyclic acetal-functionalized CLs prepared by a facile two-step reaction undergo efficient ring-opening polymerization and subsequent depolymerization. The resulting polymers demonstrate various thermal properties and a transformation of the mechanical performance from brittleness to ductility. Notably, the toughness and ductility of P(M13) is comparable to the commodity plastic isotactic polypropylene. This comprehensive study is aimed to provide a guideline to the future monomer design towards chemically recyclable polymers.
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Background: Chronic kidney disease (CKD) patients have a high prevalence of coronary artery disease and a high risk of cardiovascular events. The present study assessed the value of the CHA2DS2-VASc score for predicting mortality among hospitalized acute coronary syndrome (ACS) patients with CKD. Methods: This was a retrospective cohort study that included CKD patients who were hospitalized for ACS from January 2015 to May 2020. The CHA2DS2-VASc score for each eligible patient was determined. Patients were stratified into two groups according to CHA2DS2-VASc score: <6 (low) and ≥6 (high). The primary endpoint was all-cause mortality. Results: A total of 313 eligible patients were included in the study, with a mean CHA2DS2-VASC score of 4.55 ± 1.68. A total of 220 and 93 patients were assigned to the low and high CHA2DS2-VASc score groups, respectively. The most common reason for hospitalization was unstable angina (39.3%), followed by non-ST-elevation myocardial infarction (35.8%) and ST-elevation myocardial infarction (24.9%). A total of 67.7% of the patients (212/313) received coronary reperfusion therapy during hospitalization. The median follow-up time was 23.0 months (interquartile range: 12-38 months). A total of 94 patients (30.0%) died during follow-up. The high score group had a higher mortality rate than the low score group (46.2 vs. 23.2%, respectively; p < 0.001). The cumulative incidence of all-cause death was higher in the high score group than in the low score group (Log-rank test, p < 0.001). Multivariate Cox regression analysis indicated that CHA2DS2-VASc scores were positively associated with all-cause mortality (hazard ratio: 2.02, 95% confidence interval: 1.26-3.27, p < 0.001). Conclusion: The CHA2DS2-VASc score is an independent predictive factor for all-cause mortality in CKD patients who are hospitalized with ACS. This simple and practical scoring system may be useful for the early identification of patients with a high risk of death.
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BACKGROUND AND AIMS: Patients with chronic kidney disease (CKD) have high residual risk of cardiovascular events, whether the residual risk is associated with elevated level of lipoprotein(a) [Lp(a)] is unascertained. We aimed to explore the impact of Lp(a) levels on the risk of major adverse clinical events (MACEs) in CKD patients hospitalized for acute coronary syndrome (ACS) compared to those without CKD. METHODS: The data of patients hospitalized for ACS were collected at the China-Japan Friendship Hospital from January 2015 to December 2019. Patients were divided into 2 groups according to renal function: non-CKD group (eGFR≥60 ml/min/1.73 m2) and CKD group (eGFR <60 ml/min/1.73 m2). Multivariate Cox regression analysis and restricted cubic splines were performed to explore the relationship between Lp(a) levels and MACEs. RESULTS: A total of 1306 patients were enrolled. Patients with CKD had higher Lp(a) concentrations compared with those without CKD. During a median follow-up of 3.9 years, an elevated Lp(a) value was an independent predictor for MACEs in the overall population. Patients with a high Lp(a) level had higher risk of MACEs than those with a low Lp(a) level, regardless of renal function. The association between higher Lp(a) levels and MACEs remained consistent using the cut-off value of median (11.57 mg/dL), 30 mg/dL and 50 mg/dL in patients with CKD. On the contrary, Lp(a) higher than 50 mg/dL was associated with significantly higher risk of MACEs in patients without CKD. CONCLUSIONS: We confirmed that a high Lp(a) level was associated with long term adverse outcomes in ASC patients, especially in those with CKD.
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Síndrome Coronariana Aguda , Insuficiência Renal Crônica , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/diagnóstico , Progressão da Doença , Humanos , Lipoproteína(a) , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Fatores de RiscoRESUMO
Background: Coronary microvascular dysfunction (CMD) is a pathophysiological feature of diabetic heart disease. However, whether sodium-glucose cotransporter 2 (SGLT2) inhibitors protect the cardiovascular system by alleviating CMD is not known. Objective: We observed the protective effects of empagliflozin (EMPA) on diabetic CMD. Materials and methods: The mice were randomly divided into a db/db group and a db/db + EMPA group, and db/m mice served as controls. At 8 weeks of age, the db/db + EMPA group was given empagliflozin 10 mg/(kgâ d) by gavage for 8 weeks. Body weight, fasting blood glucose and blood pressure were dynamically observed. Cardiac systolic and diastolic function and coronary flow reserve (CFR) were detected using echocardiography. The coronary microvascular structure and distribution of cardiac pericytes were observed using immunofluorescence staining. Picrosirius red staining was performed to evaluate cardiac fibrosis. Results: Empagliflozin lowered the increased fasting blood glucose levels of the db/db group. The left ventricular ejection fraction, left ventricular fractional shortening, E/A ratio and E/e' ratio were not significantly different between the three groups. CFR was decreased in the db/db group, but EMPA significantly improved CFR. In contrast to the sparse and abnormal expansion of coronary microvessels observed in the db/db group, the number of coronary microvessels was increased, and the capillary diameter was decreased in the db/db + EMPA group. The number and microvascular coverage of cardiac pericytes were reduced in the db/db mice but were improved by EMPA. The cardiac fibrosis was increased in db/db group and may alleviate by EMPA. Conclusion: Empagliflozin inhibited CMD and reduced cardiac pericyte loss in diabetic mice.
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BACKGROUND: ST-segment elevation myocardial infarction (STEMI) patients with a high thrombus burden have a relatively high slow-flow/no-reflow risk. However, the association between kaolin-induced maximum amplitude (MAthrombin) and slow-flow/no-reflow has been scarcely explored. METHODS: STEMI patients treated with primary percutaneous coronary intervention (PCI) were retrospectively enrolled from January 2015 to December 2019 at China-Japan Friendship Hospital. MAthrombin levels were measured using thromboelastography before the PCI procedure. The patients were divided into two groups according to thrombolysis in myocardial infarction (TIMI) flow grade after primary PCI: the normal flow group (TIMI flow grade = 3) and slow-flow/no-reflow (TIMI flow grade ≤ 2). The logistic regression model and restricted cubic spline regression (RCS) were used to analyze the predictive value of MAthrombin for slow-flow/no-reflow. All patients were followed up after discharge and observed the adverse cardiovascular events between the two groups. RESULTS: A total of 690 patients were enrolled, with 108(15.7%) having slow-flow/no-reflow. The multivariate logistic regression model analysis showed that MAthrombin level was an independent risk factor for slow-flow/no-reflow. The RCS analysis showed a nonlinear relationship between MAthrombin levels and slow-flow/no-reflow. The cut-off value of MAthrombin levels for predicting slow-flow/no-reflow was 68 mm. During a median follow-up time of 4.4 years, slow-flow/no-reflow (hazard ratio 1.93, 95% confidence interval 1.27-2.93, P = 0.002) and MAthrombin levels (hazard ratio 1.06, 95% confidence interval 1.03-1.08, P < 0.001) were independent risk factors for predicting the long-term of adverse clinical cardiovascular events. CONCLUSION: MAthrombin was an independent risk factor for predicting slow-flow/ no-reflow in STEMI patients who underwent primary PCI.
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Fenômeno de não Refluxo , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Angiografia Coronária/efeitos adversos , Humanos , Caulim , Fenômeno de não Refluxo/diagnóstico , Fenômeno de não Refluxo/epidemiologia , Fenômeno de não Refluxo/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Estudos Retrospectivos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , TrombinaRESUMO
Developing a three-dimensional (3D) visualization of the kidney at the whole-mount scale is challenging. In the present study, we optimized mouse whole-mount kidney clearing, which improved the transparency ratio to over 90% based on organ-specific perfusion (OSP)-clear, unobstructed brain imaging cocktails and computational analysis (CUBIC). The optimized OSP-CUBIC-compatible 3D immunostaining and imaging simultaneously visualized the high-resolution 3D structure of the whole-mount renal microvascular, glomerulus, and accompanying wrapped traveling sympathetic nerves in mice. A mouse model of pressure overload-induced heart failure (HF) was then established by minimally invasive transverse aortic constriction (MTAC). Further 3D quantification revealed renal sympathetic hyperinnervation (6.80 ± 1.04% vs. 3.73 ± 0.60%, P < 0.05) in mice with HF. In conclusion, this newly developed whole-organ tissue clearing and imaging system provides comprehensive information at the whole-mount scale and has great potential for kidney research. Our data suggest that renal sympathetic hyperinnervation is involved in HF associated with renal dysfunction.
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OBJECTIVE: Our study aims to investigate the role of the ABO blood group in the development and severity of coronary artery disease (CAD) in end-stage renal disease (ESRD) patients with dialysis. METHODS: A total of 408 ESRD patients with dialysis between January 2010 and December 2020 were enrolled including 204 patients diagnosed with CAD undergoing coronary angiography for the first time, and baseline characteristics as well as Gensini score (GS) were collected. Logistic regression analysis and linear regression analysis were performed to evaluate the relation of ABO blood types to the risk and severity of CAD, respectively. RESULTS: Blood group O frequency was significantly low in dialysis ESRD patients with CAD (25 vs. 38.24%) compared with the non-CAD patients and multivariable logistic regression showed blood group O was negatively associated with the risk of CAD [adjusted odds ratio (OR) = 0.33, 95% CI = 0.19-0.60, p < 0.001] as well as the GS tertiles (adjusted OR = 0.23, 95% CI = 0.11-0.49, p < 0.001) compared with A blood group. Blood group A, B, and AB were positively associated with the high Gensini tertile compared with O blood group (adjusted OR = 4.26, 95% CI = 2.03-8.93, p < 0.001; adjusted OR = 2.39, 95% CI = 1.11-5.13, p < 0.05; adjusted OR = 4.33, 95% CI = 1.40-13.35, P < 0.05). Similarly, multivariable linear regression results revealed O blood type was negatively associated with the GS (ß = -26.129, 95% CI = -40.094 to -12.164, p < 0.001). CONCLUSION: This case-control study demonstrated that blood group O was a potential independent protective factor for the risk and severity of CAD in ESRD patients with dialysis.
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Thoracic aortic dissection (TAD) is a life-threatening disease that is characterized by an inflammatory response. Innate and cellular immunity has long been known to be involved in TAD, but the role of humoral immunity in the pathophysiology of TAD remains unknown. We administered the lysyl oxidase inhibitor ß-aminopropionitrile (BAPN; 1 g/kg/day) in 3-week-old male C57BL/6J mice for 4 weeks to establish an animal model of TAD. Animals that died were immediately dissected. Animals that survived were sacrificed on days 7, 14, and 28 after BAPN challenge. The incidence and rupture rates of BAPN-induced TAD were 90% (9/10) and 70% (7/10), respectively, at 28 days. Victoria blue-nuclear fast red staining of aortic tissue revealed elastic lamellae destruction and the formation of a false lumen in the BAPN group. Hematoxylin-eosin staining revealed the infiltration of both plasmacytoid mononuclear cells and polymorphonuclear inflammatory cells in TAD tissues. Enzyme-linked immunosorbent assay and immunohistochemistry indicated that plasma immunoglobin M (IgM) and IgG were elevated at 7, 14, and 28 days, and CD19-positive B cells infiltrated into the adventitia of aortic tissue in BAPN-treated mice. The transcriptional analysis showed an increase in the expression of B cell receptor signaling-associated genes. These results indicate that B cells and immunoglobulins might participate in the pathogenesis of TAD, suggesting that humoral immunity may be a possible therapeutic target for TAD.
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Aminopropionitrilo/toxicidade , Aorta Torácica/fisiopatologia , Dissecção Aórtica/fisiopatologia , Linfócitos B/fisiologia , Proteína-Lisina 6-Oxidase/antagonistas & inibidores , Dissecção Aórtica/induzido quimicamente , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND: Lifestyle behaviors significantly impact health, yet remain poorly defined in Chinese rural-to-urban migrants. METHODS: In a cross-sectional study of health-related behaviors of 5484 rural-to-urban migrants who had worked in Shanghai for at least six months, we assessed the contribution of demographics and physical and mental health to lifestyle behaviors in male and female participants by multiple stepwise cumulative odds logistic regression. RESULTS: Respondents were 51.3% male. 9.9% exhibited abnormal blood pressure; 27.0% were overweight or obese; 11.2% reported abnormal mental health; 36.9% reported healthy lifestyle. Multiple stepwise cumulative odds logistic regression indicated that men working in manufacturing reported less unhealthy lifestyle than those in hospitality (cumulative odds ratio (COR) = 1.806, 95%CI 1.275-2.559) or recreation/leisure (COR = 3.248, 95%CI 2.379-4.435); and women working in manufacturing and construction reported less unhealthy lifestyle than those in all other sectors. Unhealthy lifestyle was associated with small workplaces for men (COR = 1.422, 95%CI 1.154-1.752), working more than 8 or 11 hours per day for women and men, respectively, and earning over 3500 RMB in women (COR = 1.618, 95%CI 1.137-2.303). Single women and women who had previously resided in three or more cities were more likely to report unhealthy lifestyle (COR = 2.023, 95%CI 1.664-2.461, and COR = 1.311, 95%CI 1.072-1.602, respectively). Abnormal mental status was also correlated with unhealthy lifestyle in men (COR = 3.105, 95%CI 2.454-3.930) and women (COR = 2.566, 95%CI 2.024-3.252). CONCLUSIONS: There were different risk factors of unhealthy lifestyle score in male and female rural-to-urban migrants, especially in number of cities experienced, salary, marital status, work place scale. Several demographic groups: employment sectors (e.g. hospitality and recreation/leisure), working conditions (e.g. long hours) and abnormal mental status were associated with unhealthy lifestyle behaviors in Chinese rural-to-urban migrants, and health interventions should be targeted to these groups.