Expanding the molecular grammar of polar residues and arginine in FUS prion-like domain phase separation and aggregation.

A molecular grammar governing low-complexity prion-like domains phase separation (PS) has been proposed based on mutagenesis experiments that identified tyrosine and arginine as primary drivers of phase separation via aromatic-aromatic and aromatic-arginine interactions. Here we show that additional residues make direct favorable contacts that contribute to phase separation, highlighting the need to account for these contributions in PS theories and models. We find that tyrosine and arginine make important contacts beyond only tyrosine-tyrosine and tyrosine-arginine, including arginine-arginine contacts. Among polar residues, glutamine in particular contributes to phase separation with sequence/position-specificity, making contacts with both tyrosine and arginine as well as other residues, both before phase separation and in condensed phases. For glycine, its flexibility, not its small solvation volume, favors phase separation by allowing favorable contacts between other residues and inhibits the liquid-to-solid (LST) transition. Polar residue types also make sequence-specific contributions to aggregation that go beyond simple rules, which for serine positions is linked to formation of an amyloid-core structure by the FUS low-complexity domain. Hence, here we propose a revised molecular grammar expanding the role of arginine and polar residues in prion-like domain protein phase separation and aggregation.

Neutrophil to high-density lipoprotein cholesterol ratio predicts adverse cardiovascular outcomes in subjects with pre-diabetes: a large cohort study from China.

BACKGROUND: This study aimed to examine whether the neutrophil to high-density lipoprotein cholesterol ratio (NHR) can predict cardiovascular outcomes in normoglycemic individuals with elevated fasting glucose levels. METHODS: A total of 130,801 participants with normal blood glucose levels were enrolled in the Kailuan study. Participants were categorized according to NHR quartiles and further divided into normal glucose regulation (NGR) and pre-diabetes (pre-DM) subgroups. The follow-up endpoint was major adverse cardiovascular events (CVE), including stroke and myocardial infarction. RESULTS: Over a median of 12.53 (8.95-13.08) years of follow-up, subjects with NHR levels in the highest quartile experienced more CVE than those with NHR levels in the lowest quartile. Multivariate Cox analyses showed that continuous changes in NHR (hazard ratio, 1.21; 95% confidence interval [CI], 1.15-1.28) and the highest quartile of NHR (hazard ratio, 1.30; 95% CI, 1.21-1.39) were independent predictors of CVE (all P < 0.001). Furthermore, when participants were categorized by both NHR quartile and glucose metabolism status, the NHR level in the highest quartile plus pre-DM group was associated with a 1.60-fold (95% CI, 1.38-1.86; P < 0.001] higher risk of CVE than that in the lowest quartile plus normoglycemic group. Significantly, the addition of NHR only, presence of pre-DM only, or combination of NHR and pre-DM to the prediction algorithm, including traditional risk factors, improved the C-statistic by 0.19, 0.05, and 0.23 (all P < 0.001). CONCLUSIONS: Elevated NHR or fasting blood glucose level were independently associated with a higher risk of CVE among normoglycemic individuals. Moreover, pre-DM participants with high NHR levels tended to have worse prognosis, suggesting that NHR could provide greater risk stratification value than traditional risk factors for subjects with pre-DM.

Severity of Nonalcoholic Fatty Liver Disease is Associated With Cardiovascular Outcomes in Patients With Prehypertension or Hypertension: A Community-Based Cohort Study.

Background: It is unclear whether more severe non-alcoholic fatty liver disease (NAFLD) combined with prehypertension or hypertension is associated with a higher risk of cardiovascular events (CVEs). To evaluate the relationship between the severity of NAFLD and CVEs among patients with prehypertension or hypertension. Methods: In this prospective community-based Kailuan cohort, participants without cardiovascular disease and alcohol abuse, or other liver diseases were enrolled. NAFLD was diagnosed by abdominal ultrasonography. Prehypertension was defined as systolic blood pressure (BP) of 120-139 mmHg or diastolic BP of 80-89 mmHg. Participants with NAFLD were divided into mild, moderate, and severe subgroups. Follow-up for CVEs including myocardial infarction, hemorrhagic stroke, and ischemic stroke. The Cox proportional hazards model was used to estimate hazard ratios and 95% CIs of CVEs according to the severity of NAFLD and hypertensive statutes. The C-statistic was used to evaluate the efficiency of models. Results: A total of 71926 participants (mean [SD] age, 51.83 [12.72] years, 53794 [74.79%] men, and 18132 [25.21%] women) were enrolled in this study, 6,045 CVEs occurred during a median of 13.02 (0.65) years of follow-up. Compared with participants without NAFLD, the hazard ratios of CVEs for patients with mild, moderate, and severe NAFLD were 1.143 (95% CI 1.071-1.221, P < 0.001), 1.218 (95% CI 1.071-1.221, P < 0.001), and 1.367 (95% CI 1.172-1.595, P < 0.001), respectively. Moreover, participants with prehypertension plus moderate/severe NAFLD and those with hypertension plus moderate/severe NAFLD had 1.558-fold (95% CI 1.293-1.877, P < 0.001) and 2.357-fold (95% CI 2.063-2.691, P < 0.001) higher risks of CVEs, respectively, compared with those with normal BP and no NAFLD. Adding a combination of NAFLD and BP status to the crude Cox model increased the C-statistic by 0.0130 (0.0115-0.0158, P < 0.001). Conclusions: Our findings indicated that the increased cardiovascular risk with elevated BP is largely driven by the coexistence of moderate/severe NAFLD, suggesting that the severity of NAFLD may help further stratify patients with prehypertension and hypertension.

QRISK3-based analysis of cardiovascular risk factors in patients with long-term but well-controlled systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a multisystem inflammatory disease of unknown etiology. Corticosteroids and immunosuppressive agents are the principal forms of treatment for this condition. While cardiovascular disease (CVD) is known to be a major cause of death in patients with SLE, there has been no improvement over the last few decades with regard to diagnosis, treatment, or prognosis. The QRISK3 algorithm is a new algorithm that includes SLE-related risk factors; this tool can predict the risk of CVD over a ten-year period. In this study, involving 180 patients, we compared the performance of the Framingham risk score, the recalibrated risk prediction SCORE, and QRISK3 for the assessment of CVD in patients with a long course of disease and low disease activity. Then, we used a more efficient algorithm, QRISK3 to identify the risk factors for CVD. This was a prospective and cross-sectional study involving 116 patients. All patients fulfilled the ACR criteria. The systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K) is widely used to assess disease activity in SLE patients; patients with a SLEDAI-2K less than or equal to 4 are considered to be stable. Thus, we defined well-controlled patients as those with a SLEDAI-2K score less than or equal to 4. The dose of glucocorticoid (GC) that patients received was less or equal to 10 mg per day. We recorded and assessed a range of traditional risk factors, current treatments, comorbidities, data at the time of onset, and SLE-related evaluations. The QRISK3 score, and the relative risk (RR) that this score defined, were used to estimate the risk of CVD in patients with SLE. According to these relative risks, the patients were divided into low- (n=28), intermediate- (n=46), and high-relative risk (n=31) groups for subgroup analysis. Of the 116 patients enrolled, 105 were eligible to be assessed for the risk of CVD. By univariate analyses, the RR was significantly related with age at the time of enrolment (p<0.001), age at onset (p<0.001), resting heart rate (RHR) (p<0.001), present dose of GCs (p<0.001), present SLEDAI-2K (p=0.015), aerobic exercise (p<0.001), initial SLEDAI-2K (p<0.001), and initial dose of GCs (p=0.048). In the multiple linear regression model, the RR of CVD was significantly correlated with the initial SLEDAI-2K score (ß=2.112, p<0.001), initial dose of GCs (ß=-0.009, p=0.041), resting heart rate (ß=0.241, p=0.003) and age at onset (ß=-0.208, p=0.004). Pearson's correlation showed that RHR was significantly associated with aerobic exercise (r=-0.322, p=0.001). Subgroup analysis further identified a positive correlation between the history of nephritis, metabolic syndrome (MetS), aerobic exercise, present dose of GCs, and the RR of CVD. Patients with long-term but well-controlled SLE had a high relative risk of CVD and that this was associated with resting heart rate (P=0.003), history of lupus nephritis (P<0.001), initial SLEDAI-2K score (P<0.001), and metabolic syndrome (P=0.017). However, age at onset (P<0.001), use of hydroxychloroquine (P=0.30) and Mycophenolate mofetil (P=0.01), and the initial dose of glucocorticoid (P=0.049), were protective factors. Younger SLE patients had a significantly higher relative risk of CVD than older patients (p<0.001). QRISK3 detected more SLE patients at high risk of CVD when compared to the Framingham and recalibrate SCORE. To reduce the risk of CVD in SLE patients, measures should be taken both during the initial stages of disease and for long-term management.

Non-alcoholic Fatty Liver Disease Is Associated With Cardiovascular Outcomes in Subjects With Prediabetes and Diabetes: A Prospective Community-Based Cohort Study.

Background: There have been no studies of the effect of non-alcoholic fatty liver disease (NAFLD) on cardiovascular events (CVEs) in patients with pre-diabetes (pre-DM), and diabetes mellitus (DM). We performed a community-based cohort study to evaluate the relationship between NAFLD and CVEs in patients with glucose metabolism disorder. Methods: We enrolled 71,852 participants from the Kailuan study who had not experienced CVEs, after excluding alcohol abuse and other liver diseases. NAFLD was assessed using abdominal ultrasonography. Besides, participants were categorized by glucose metabolism status [normal glucose regulation (NGR), pre-DM, and DM]. All subjects were followed up for the occurrence of CVEs. Results: During a median of 13.01 (0.64) years of follow-up, 6,037 CVEs occurred. NAFLD was present in 22,525 (31.3%), and compared with participants without NAFLD, those with NAFLD had a 12.3% [95% confidence interval (CI) 1.059-1.191, P < 0.001] higher risk of CVEs, after adjustment for potential confounders. The hazard ratios for patients with mild, moderate, and severe NAFLD were 1.104 (95% CI 1.035-1.179, P < 0.001), 1.149 (95% CI 1.055-1.251, P < 0.001), and 1.235 (95% CI 1.059-1.441, P < 0.001), respectively. Moreover, participants with pre-DM plus NAFLD and participants with DM plus NAFLD had 1.267-fold (95% CI 1.151-1.395, P < 0.001) and 1.829-fold (95% CI 1.666-2.008, P < 0.001) higher risks of CVEs, respectively, compared with those with NGR and no NAFLD. The addition of the combination of NAFLD and glucose metabolism status to the crude Cox model increased the C-statistic by 0.0066 (0.0053-0.0080, P < 0.001). Conclusions: NAFLD is associated with higher risks of CVEs. Moreover, NAFLD is an independent predictor of CVEs in patients with pre-DM and DM, suggesting that NAFLD may provide greater risk predictive value for patients with glucose metabolism disorder.

Effects of Nanodroplet Sizes on Wettability, Electrowetting Transition, and Spontaneous Dewetting Transition on Nanopillar-Arrayed Surfaces.

In this study, the wetting and dewetting behaviors of water nanodroplets containing various molecule numbers on nanopillar-arrayed surfaces in the presence or absence of an external electric field are investigated via molecular dynamics (MD) simulations, aiming to examine whether there is a scale effect. The results show that, in the absence of an electric field, nanodroplets on coexisting Cassie/Wenzel surfaces may be in the Cassie or the Wenzel state depending on their initial states, and apparent contact angles of the Cassie or Wenzel nanodroplets increase monotonously with increasing the droplet size. Energy analysis shows that on the same coexisting Cassie/Wenzel surface, when an electric field is imposed, a small nanodroplet possesses a lower energy barrier separating the Cassie state from the Wenzel state. Therefore, the small nanodroplet is easier to collapse into the Wenzel state. Moreover, the spontaneous Wenzel-to-Cassie dewetting transition is not observed for the nanodroplets after the removal of the electric field because the Wenzel state is a globally stable energetic state. With the same pillar geometry, both the wetting transition and the dewetting transition are significantly modified for liquids with higher intrinsic contact angles. The energy barrier of the wetting transition increases for both the large and small nanodroplets, meaning that the Cassie state becomes more robust. The energy curve shows that the Wenzel state of the large nanodroplet has higher energy so that the droplet can return to the Cassie state when removing the electric field. Intriguingly, although the small Wenzel nanodroplet has lower energy in the presence of the electric field, the dewetting transition still occurs. The increased solid-liquid interfacial tension when removing the electric field is responsible for this abnormal result. The wetting and dewetting transitions follow different energy pathways, leading to a hysteresis energy loop. There exists a critical water molecule number separating the unstable/stable Wenzel configurations, above which the Cassie state is energetically favorable and the dewetting transition can occur spontaneously after removing the electric field.

Glycan-masking spike antigen in NTD and RBD elicits broadly neutralizing antibodies against SARS-CoV-2 variants

Glycan-masking the vaccine antigen by mutating the undesired antigenic sites with an additional N-linked glycosylation motif can refocus B-cell responses to desired/undesired epitopes, without affecting the antigens overall-folded structure. This study examine the impact of glycan-masking mutants of the N-terminal domain (NTD) and receptor-binding domain (RBD) of SARS-CoV-2, and found that the antigenic design of the S protein increases the neutralizing antibody titers against the Wuhan-Hu-1 ancestral strain and the recently emerged SARS-CoV-2 variants Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2). Our results demonstrated that the use of glycan-masking Ad-S-R158N/Y160T in the NTD elicited a 2.8-fold, 6.5-fold, and 4.6-fold increase in the IC-50 NT titer against the Alpha (B.1.1.7), Beta (B.1.351) and Delta (B.1.617.2) variants, respectively. Glycan-masking of Ad-S-D428N in the RBD resulted in a 3.0-fold and 2.0-fold increase in the IC50 neutralization titer against the Alpha (B.1.1.7) and Beta (B.1.351) variants, respectively. The use of glycan-masking in Ad-S-R158N/Y160T and Ad-S-D428N antigen design may help develop universal COVID-19 vaccines against current and future emerging SARS-CoV-2 variants.

Harnessing Reversible Wetting Transition to Sweep Contaminated Superhydrophobic Surfaces.

Sweeping deposited particles is absolutely essential in order to maintain the excellent functionality of superhydrophobic surfaces. Many methods have been proposed to sweep microparticles deposited on tips of micro/nanostructures. However, how to sweep nanoparticles trapped in cavities of superhydrophobic surfaces has remained an outstanding issue. Here, we show that harnessing the reversible wetting transition provides a feasible way to sweep such nanoparticles. Using molecular dynamics simulations, we demonstrate that the electrically induced CB-W wetting transition makes liquid intrude into a groove and wet a trapped hydrophilic nanoparticle; however, once the electric field is removed, a spontaneous W-CB dewetting transition happens, and the extruded liquid transports the hydrophilic nanoparticle to the groove top, successfully picking up the trapped hydrophilic nanoparticle. We further find that the adhesion between the nanoparticle and groove bottom wall hinders the successful pickup, and picking up such a nanoparticle requires a stronger particle hydrophilicity. With the introduction of amphiphilic Janus particles into a liquid, we exhibit that the electrically induced reversible wetting transition can also successfully pick up a trapped hydrophobic nanoparticle. By means of calculations of the potential of mean force (PMF), we reveal pathways of both the CB-W wetting transition and the W-CB dewetting transition and hence answer why and how a hydrophilic or a hydrophobic nanoparticle is picked up successfully.

The pathogenesis and treatment in antineutrophil cytoplasmic antibody associated vasculitis.

Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) is a systemic autoimmune disease characterized by leukocytoclastic inflammation of small blood vessels. Commonly detected autoantibodies include anti-protease 3 (PR3) and anti-myeloperoxidase (MPO). Although cell necrosis plays an important role in the production of autoantibodies and the pathogenesis of AAV, the correlation between their titers and disease activity remains elusive. As improved detection techniques facilitate early diagnosis, a satisfactory efficacy can be achieved in patients with mild to medium severe AAV treated with glucocorticoids and immunosuppressants. However, resistant and relapsing AAV, sometimes life-threatening, do exist in clinical practice. In-depth understanding of pathogenesis of AAV may lend novel insight into the mechanism responsible for its formation and help find effective targeted therapies for refractory patients.

Association of serum lipoprotein(a) level with the severity and prognosis of calcific aortic valve stenosis: a Chinese cohort study.

BACKGROUND: There was a causal relationship between elevated lipoprotein(a) [Lp(a)] levels and increased risk of calcific aortic valve stenosis (CAVS) in whites and blacks. The present study aimed to investigate whether Lp(a) levels were associated with aortic stenosis (AS) severity and clinical events in Chinese patients. METHODS: Levels of serum Lp(a) were measured in 652 patients with CAVS, whom all underwent baseline echocardiographic examination. The clinical endpoint was defined as a composite of aortic valve replacement (AVR) and cardiac death. RESULTS: Patients in the tertile 3 of Lp(a) had a higher percentage of severe AS compared with those in the tertile 1 and 2 of Lp(a) (46.2% vs. 33.9%, P = 0.005). Moreover, the top tertile of Lp(a) was an independent predictor of severe AS (OR = 1.78, 95% CI: 1.18-2.66, P = 0.006). However, there was no significant association between tertile 3 of Lp(a) and clinical events (hazard ratio: 0.73; 95% CI: 0.43-1.24; P = 0.239) in the multivariate Cox regression analysis during a mean follow-up time of 3.16 ± 2.74 years. CONCLUSIONS: Elevated Lp(a) level was an independent predictor of severe AS by echocardiography in the Chinese population, but was not associated with the increased risk of AVR and cardiac death, suggesting that Lp(a) levels might be helpful in the risk stratification of patients with CAVS.

Fibrinogen is associated with glucose metabolism and cardiovascular outcomes in patients with coronary artery disease.

BACKGROUND: The present cohort study aims to examine the relationship between fibrinogen (Fib) levels and glucose metabolism [fasting blood glucose (FBG) and hemoglobin A1c (HbA1c)] and investigate the impact of high Fib on cardiovascular outcomes in patients with stable CAD and pre-diabetes mellitus (pre-DM) or diabetes mellitus (DM). METHODS: This study included 5237 patients from March 2011 to December 2015. Patients were distributed into three groups according to Fib levels (low Fib, median Fib, high Fib) and further categorized by glucose metabolism status [normal glucose regulation (NGR), Pre-DM, DM]. All patients were followed up for the occurrences of major adverse cardiovascular events (MACEs), including cardiovascular mortality, nonfatal MI, stroke, and unplanned coronary revascularization. RESULTS: Linear regression analyses showed that FBG and HbA1c levels were positively associated with Fib in overall CAD participants, either with or without DM (all P < 0.001). During an average of 18,820 patient-years of follow-up, 476 MACEs occurred. High Fib was independently associated with MACEs after adjusting for confounding factors [Hazard Ratio (HR): 1.57, 95% confidence interval (CI) 1.26-1.97, P < 0.001]. Furthermore, DM but not pre-DM was a significant predictor of MACEs (P < 0.001 and P > 0.05, respectively). When patients were stratified by both glucose metabolism status and Fib levels, high Fib was associated with a higher risk of MACEs in pre-DM (HR 1.66, 95% CI 1.02-2.71, P < 0.05). Medium and high Fib levels were associated with an even higher risk of MACEs in DM (HR 1.86, 95% CI 1.14-3.05 and HR 2.28, 95% CI 1.42-3.66, all P < 0.05). After adding the combination of Fib and glucose status to the Cox model, the C-statistic was increased by 0.015 (0.001-0.026). CONCLUSIONS: The present study suggested that Fib levels were associated with FBG and HbA1c in stable CAD patients. Moreover, elevated Fib was independently associated with MACEs in CAD patients, especially among those with pre-DM and DM, suggesting that Fib may provide incremental value in the cardiovascular risk stratification of pre-DM and DM patients.

Experimental study of a modified extraction method of mouse islets / 器官移植

Objective To investigate the improvement and effect of the method of islet extraction in mice. Methods According to different islet extraction methods, all mice were randomly divided into the common bile duct puncture group (n=100) and common bile duct puncture combined with in situ pancreatic injection group (combined injection group, n=100). Common bile duct puncture combined with in situ pancreatic injection was utilized as the modified method. The islets were selected and purified under stereomicroscope. The morphology and purification of islets were identified. The islet yield and success rate of islet extraction were statistically compared between two groups. The survival of islets after 1 week culture in vitro was analyzed, and the insulin secretion function of islets after 24 h and 4 d culture in vitro was evaluated. Results Compared with the common bile duct puncture group, the islet yield in the combined injection group was significantly increased (P < 0.001). The success rate of islet extraction in both groups was 83% with no statistical significance (P > 0.05). The islets extracted by common bile duct puncture combined with in situ pancreatic injection had intact morphology, high purity and high activity. The survival rate of newly isolated islets was nearly 100% after 24 h culture in vitro. After 1~5 d culture in vitro, the islet cells survived well. After 6 d culture in vitro, the islets showed central death. After culture in vitro for 24 h and 4 d, the islet function of the mice was normal after high glucose stimulation. Conclusions Common bile duct puncture combined with in situ pancreatic injection can increase the islet yield, and the obtained islet cells have high activity and proper function.

Lipoprotein(a) and coronary artery disease in Chinese postmenopausal female patients: a large cross-sectional cohort study.

BACKGROUND: It has been reported that lipoprotein(a) (Lp(a)) is associated with the risk of cardiovascular disease. The present study aimed to examine the association of Lp(a) levels with the presence and severity of coronary artery disease (CAD) in female patients. METHODS: A total of 3712 female patients who received coronary angiography were consecutively enrolled. The levels of Lp(a) were measured and compared among patients with or without CAD, myocardial infarction and menopause. Spearman correlation analysis and logistic regression analysis were used to examine the association of Lp(a) with the presence of CAD and the severity of coronary atherosclerosis assessed by Gensini score (GS). RESULTS: The average of Lp(a) levels was elevated as age increased in female subjects. Notably, women after menopause had higher Lp(a) levels compared with that before menopause (16.8 mg/dL (IQR 7.54-41.12 mg/dL) vs 14.7 mg/dL (IQR 6.72-30.82 mg/dL), p=0.002). Furthermore, multiple logistic regression analysis identified that Lp(a)>30 mg/dL was an independent risk factor of CAD in the postmenopausal females (OR: 1.33, 95% CI: 1.08 to 1.63, p=0.007). Finally, Lp(a) had a positive correlation with GS (r=0.11, p<0.001), and Lp(a)>30 mg/dL was an independent risk factor for high GS (OR: 1.43, 95% CI: 1.14 to 1.79, p=0.02) in the postmenopausal females. CONCLUSION: Circulating Lp(a) levels were independently associated with the presence and severity of CAD in the postmenopausal females, suggesting that Lp(a) may be useful for prevention and risk-stratification of CAD in female individuals.

Wetting Transition from the Cassie-Baxter State to the Wenzel State on Regularly Nanostructured Surfaces Induced by an Electric Field.

When droplets are placed on hydrophobic textured surfaces, different wetting states Cassie-Baxter (CB) state or Wenzel (W) state may occur depending on materials and structures of surfaces, types and sizes of droplets, thermal fluctuations, and external stimuli. The wetting transition from the CB to the W state and the opposite process have attracted a great deal of attention because of their primary importance for designing and fabricating textured surfaces. In this work, molecular dynamics (MD) simulations are employed to understand the mechanism behind the CB-to-W transition for a nanoscale water film placed on a surface decorated with a single nanogroove when an external electric field is applied. The free energy variation during the transition process is computed on the basis of the restrained MD simulations. Water intrusion into the groove is observed by simulation snapshots, which provides direct evidence for the electric field-induced CB-to-W transition. In the previous experiments, however, only a sharp reduction in the apparent contact angle is employed to judge whether the transition takes place. The free energy curves reveal that there are two energy barriers separating the CB and W states (Δ E1) as well as separating the W and CB states (Δ E2). Owing to the presence of Δ E1, although the CB state has a higher free energy than the W state, it cannot spontaneously convert to the W state. When the external energy input exceeds Δ E1, the CB-to-W transition can be triggered, otherwise the transition will stop, and the water film will return to the CB state. Moreover, it is found that the maximum of free energy always occurs after the film touches the groove bottom. Thus, the requirement that the film should touch the groove bottom is responsible for the presence of the energy barrier Δ E1. Finally, the dependence of the two energy barriers on the electric field strength, groove aspect ratio, and intrinsic contact angle of the groove is also discussed.

Prognostic Value of Combined C-Reactive Protein, Body Mass Index, and Left Ventricular Ejection Fraction in Predicting Cardiovascular Events in Patients ≥80 Years of Age With Acute Myocardial Infarction.

Elevated high-sensitivity C-reactive protein (hsCRP) and low body mass index (BMI) are linked to increased mortality in the elderly population. However, the combined value for predicting adverse cardiovascular events in the oldest-old (≥80 years old) with acute myocardial infarction (AMI) remains undetermined. A total of 463 AMI patients, who were ≥80 years old, were enrolled in this study between January 2012 and June 2017. A nested case-control study was implemented in 106 deaths and 212 controls, who were matched for age, gender, time of inclusion, and myocardial infarction type. Furthermore, the individual and additive values of hsCRP, BMI, and left ventricular ejection fraction (LVEF) were assessed using adjusted hazard ratio, unadjusted Kaplan-Meier analysis, and receiver-operating characteristic curve models. The median follow-up time was 19.15 months, and there were 106 deaths (33.3%). Furthermore, HsCRP, BMI, and LVEF were significantly associated with all-cause mortality (p <0.05, respectively). In addition, a negative correlation between BMI and LVEF, and the positive association of hsCRP with all-cause mortality in the fully adjusted Cox proportional hazards model were detected. The combination of hsCRP, BMI, and LVEF was found to exhibit an enhanced predictive value for all-cause mortality (0.733 in jointly vs 0.623 in cardiovascular risk factors, p = 0.0007) in these oldest-old AMI patients. HsCRP, BMI, and LVEF are the independent risk factors for all-cause mortality for the oldest-old patients with AMI, and this combination offers more appreciable and reliable predictive value for all-cause mortality.

Association of invasive treatment and lower mortality of patients ≥ 80 years with acute myocardial infarction: a propensity-matched analysis.

OBJECTIVE: To investigate whether invasive strategy was associated with lower mortality in Chinese patients ≥ 80 years with acute myocardial infarction (AMI). METHODS: We used retrospective data from our center between 2013 and 2017. During a median of 17.4 (interquartile range: 7.3-32.3) months follow-up, 120 deaths were recorded among 514 consecutive patients ≥ 80 years with AMI. The patients were divided into two groups: invasive treatment group (IT group, n = 269) and conservative treatment group (CT group, n = 245), which were also then compared with propensity score matching. RESULTS: High mortality was found in CT group compared with that in the IT one. Cox proportional hazard regression analysis showed that invasive treatment was associated with lower mortality of patients ≥ 80 years. Moreover, the results revealed that the patients in IT group had lower in-hospital mortality (3.35% vs. 9.39%, P = 0.005). Besides, the Kaplan-Meier analysis revealed that the mortality was significantly lower in IT group compared with that in CT group using entire and propensity-matched cohort analysis (P < 0.001, respectively). CONCLUSIONS: Our data suggested that IT appeared to be associated with lower mortality in Chinese patients ≥ 80 years with AMI, which consists with previous studies in spite of either ST elevated myocardial infarction (STEMI) or non-STEMI (NSTEMI) patients.

Effect of Resveratrol on Blood Rheological Properties in LPS-Challenged Rats.

Objectives: Abnormal rheological properties induce adverse effects during sepsis. This study sought to investigate the hypothesis that resveratrol (Res) improves blood rheological properties in rats following a lipopolysaccharide (LPS) challenge, and provide a novel approach for treatment of sepsis. Methods: The rats were intraperitoneally or intramuscularly injected with vehicle, LPS (8 mg/kg), Res (30 mg/kg), or both to yield four groups: control, Res, LPS, and LPS + Res. After 6 h of LPS and/or Res injection, the mean arterial pressure (MAP), regional blood flow, erythrocyte and leukocyte parameters, and blood viscosity were observed. Results: LPS administration had no significant effects on the erythrocyte parameters and plasma viscosity. LPS administration reduced the MAP, whole blood viscosity at low and medium shear rates, the blood flow in the spleen and kidney, and the leukocyte content in whole blood when compared to control group, and increased the myeloperoxidase (MPO) activity in lung. Treatment with Res alone had no effects on most of parameters observed except increasing the whole blood relative viscosity. However, Res treatment after LPS resulted in further decrease in whole blood viscosity at high and medium shear rates. Furthermore, Res treatment conversely decreased the red blood cell distribution width-CV, blood flow of stomach, whole blood relative viscosity and MPO activity in lung, and increased the leukocyte content, but did not restore LPS-induced decrease in MAP and the blood flow in the spleen and kidney. Conclusion: The Res treatment partly reduce the whole blood viscosity and regional blood flow, and increase WBC content in peripheral blood following the LPS challenge, suggesting a favorable role in expanding the quasi-sympathetic effects of LPS in blood viscosity at early stages.

Cognitive behavioral therapy for post-stroke depression: A meta-analysis.

BACKGROUND: Cognitive behavioral therapy (CBT) has been widely used for post-stroke depression (PSD), but the findings have been inconsistent. This is a meta-analysis of randomized controlled trials (RCTs) of CBT for PSD. METHODS: Both English (PubMed, PsycINFO, Embase) and Chinese (WanFang Database, Chinese National Knowledge Infrastructure and SinoMed) databases were systematically searched. Weighted and standardized mean differences (WMDs/SMDs), and the risk ratio (RR) with their 95% confidence intervals (CIs) were calculated using the random effects model. RESULTS: Altogether 23 studies with 1,972 participants with PSD were included and analyzed. Of the 23 RCTs, 39.1% (9/23) were rated as high quality studies, while 60.9% (14/23) were rated as low quality. CBT showed positive effects on PSD compared to control groups (23 arms, SMD = -0.83, 95% CI: -1.05 to -0.60, P < 0.001). Both CBT alone (7 arms, SMD = -0.76, 95% CI: -1.22 to -0.29, P = 0.001) and CBT with antidepressants (14 arms, SMD = -0.95, 95% CI: -1.20 to -0.71, P < 0.00001) significantly improved depressive symptoms in PSD. CBT had significantly higher remission (6 arms, RR = 1.76, 95% CI: 1.37-2.25, P < 0.00001) and response rates (6 arms, RR = 1.41, 95% CI: 1.22-1.63, P < 0.00001), with improvement in anxiety, neurological functional deficits and activities of daily living. CBT effects were associated with sample size, mean age, proportion of male subjects, baseline depression score, mean CBT duration, mean number of CBT sessions, treatment duration in each session and study quality. CONCLUSION: Although this meta-analysis found positive effects of CBT on depressive symptoms in PSD, the evidence for CBT is still inconclusive due to the limitations of the included studies. Future high-quality RCTs are needed to confirm the benefits of CBT in PSD.

Association of Polymorphisms in CAV1/CAV2 Locus with Type 2 Diabetes in Chinese Han Population / 中山大学学报(医学科学版)

[Objective]To study the association of CAV1/CAV2 gene polymorphisms with type 2 diabetes in Chinese Han population.[Methods]14 single nucleotide polymorphisms(SNPs)of CAV1/CAV2 gene were genotyped in 272 pa-tients with type 2 diabetes mellitus(T2DM group)and 287 subjects with normal glucose tolerance(control group)by ma-trix-assisted laser desorption ionization-time of flight-mass spectrometry(MALDI-TOF-MS).Waist circumference,body mass index,plasma glucose,serum insulin and lipid profiles were measured.Homeostatic model assessment of insulin resis-tance(HOMA-IR)and β-cell function(HOMA-β)were calculated.[Results]The minor allele frequency(MAF)distri-butions of CAV1 rs926198,CAV2 rs2270188,and rs1052990 were significantly different between T2DM group and con-trol group(P=0.008,0.021,and 0.045,respectively). After adjusting for age,gender,and BMI,logistic regression analysis showed that minor allele carriers(CC/CT genotype)of CAV1 rs926198 displayed a particularly increased risk of developing T2DM compared to major allele homozygotes(TT genotype)(OR=2.240,95% CI=1.415-3.544,P=0.001). GG/GA genotype carriers of CAV1 rs3807986 had lower odds for T2DM than that of AA genotype(OR=0.640,95% CI=0.449-0.913,P=0.014). Compared with TT genotype,GG/GT genotype of CAV2 rs2270188 was a protective factor for T2DM(OR=0.616,95% CI=0.432-0.878,P=0.007). Significant genotype association with T2DM was also identified in CAV2 rs1052990(GG/GT versus TT genotype:OR=0.658,95% CI=0.453-0.956,P=0.028). Multiple linear regression showed that minor allele C of SNP rs926198 was associated with an increased level of HOMA-IR(beta=1.010,P<0.001) and minor allele G of SNP rs2270188 was associated with a decreased level of HOMA-IR(beta=-0.379,P=0.023). No significant association was identified between any SNP and HOMA-β.Allele G of CAV1 rs3807986 and CAV2 rs2270188 were also associated with a decreased level of LDL-C(P=0.033 and 0.030,respectively).[Conclusion]CAV1/CAV2 locus might be the candidate genes for conferring susceptibility to T2DM in the Chinese Han population.SNP rs926198, rs3807986,rs2270188,and rs1052990 in CAV1/CAV2 locus were associated with T2DM risk perhaps through insulin resistance pathway.

Fabrication of Stable and Regenerable Amine Functionalized Magnetic Nanoparticles as a Potential Material for Pt(IV) Recovery from Acidic Solutions.

MnFe2O4@SiO2-NH2 magnetic nanocomposite (AFMNC) adsorbent with a particle size of ∼50 nm was successfully synthesized using a facile approach. The as-prepared composite particles showed a fast binding of Pt(IV) with easy magnetic solid-liquid separation. The kinetic data were fitted to both pseudo-first and second-order rate models, indicating that AFMNC exhibited a much higher rate of Pt(IV) binding (0.125 g mg-1 min-1) compared to that of commercial ion-exchange resin Amberjet 4200 (0.0002 g mg-1 min-1). The equilibrium adsorption data were fitted to the Langmuir isotherm model with a relatively high sorption capacity of 380 mg/g. Scanning transmission electron microscopy analysis demonstrated the presence of platinum chloride after sorption on AFMNC, suggesting an adsorbate-adsorbent anion-exchange interaction. In addition, due to its magnetic characteristics, AFMNC can be easily separated from the aqueous medium after the sorption process. The novel nanocomposite may facilitate recovery of Pt(IV) from waste solutions.