Tetramethylpyrazine and paeoniflorin combination(TMP-PF)alleviates atherosclerosis progress by reducing hyperlipemia and inhibiting plaque angiogenesis via the NR4A1/VEGFR2 pathway

Atherosclerosis remains a great threat to human health worldwide.Previous studies found that tetramethylpyrazine(TMP)and paeonifl orin(PF)combination(TMP-PF)exerts anti-atherosclerotic effects in vitro.However,whether TMP-PF improves atherosclerosis in vivo needs further exploration.The present study aims to assess the anti-atherosclerotic properties of TMP-PF in ApoE^(-/-)mice and explore the related molecule mechanisms.Results showed that TMP and high-dose TMP-PF decreased serum triglyceride and low-density lipoprotein cholesterol levels,suppressed vascular endothelial growth factor receptor 2(VEGFR2)and nuclear receptor subfamily 4 group A member 1(NR4A1)expression in aortic tissues,inhibited plaque angiogenesis,reduced plaque areas,and alleviated atherosclerosis in ApoE^(-/-)mice.Also,TMP-PF exhibited a better modulation effect than TMP or PF alone.However,NR4A1 agonist abolished the anti-atherosclerotic effects of TMP-PF.In conclusion,TMP-PF was first found to alleviate atherosclerosis progression by reducing hyperlipemia and inhibiting plaque angiogenesis via the NR4A1/VEGFR2 pathway,indicating that TMP-PF had a positive effect on reducing hyperlipemia and attenuating atherosclerosis development.

Treatment of type 2 diabetes mellitus in the elderly

The prevalence of type 2 diabetes is expected to increase gradually with the prolongation of population aging and life expectancy. In addition to macrovascular and microvascular complications of elderly patients of diabetes mellitus, geriatric syndromes such as cognitive impairment, depression, urinary incontinence,falling and polypharmacy are also accompanied by aging. Individual functional status in the elderly shows heterogeneity so that in these patients, there are many unanswered questions about the management of diabetes treatment. The goals of diabetes treatment in elderly patients include hyperglycemia and risk factors, as in younger patients. comorbid diseases and functional limitations of individuals should be taken into consideration when setting treatment targets. Thus, treatment should be individualized. In the treatment of diabetes in vulnerable elderly patients, hypoglycemia, hypotension, and drug interactions due to multiple drug use should be avoided. Since it also affects the ability to self-care in these patients, management of other concurrent medical conditions is also important.

Combination of allopurinol and hyperbaric oxygen therapy:A new treatment in experimental acute necrotizing pancreatitis?

AIM： To investigate the individual and combined effects of allopurinol and hyperbaric oxygen （HBO） therapy on biochemical and histopathological changes, oxidative stress, and bacterial translocation （BT） in the experimental rat acute pancreatitis （AP）. METHODS： Eighty-five Sprague-Dawley rats were included in the study. Fifteen of the eighty-five rats were used as controls （sham, Group I ）. AP was induced via intraductal taurocholate infusion in the remaining seventy rats. Rats that survived to induction of acute necrotizing pancreatitis were randomized into four groups. Group H received saline, Group m allopurinol, Group IV allopurinol plus HBO and Group v HBO alone. Serum amylase levels, oxidative stress parameters, BT and histopathologic scores were determined. RESULTS： Serum amylase levels were lower in Groups Ⅲ, Ⅳ and v compared to Group H （974 ± 110, 384 ± 40, 851 ＋ 56, and 1664 Ⅳ 234 U/L, respectively, P 〈 0.05, for all）. Combining the two treatment optionsrevealed significantly lower median [25-75 percentiles] histopathological scores when compared to individual administrations （13 [12.5-15] in allopurinol group, 9.5 [7-11.75] in HBO group, and 6 [4.5-7.5] in combined group, P 〈 0.01）. Oxidative stress markers were significantly better in all treatment groups compared to the controls. Bacterial translocation into the pancreas and mesenteric lymph nodes was lower in Groups m, iV and v compared to Group H （54%, 23%, 50% vs 100% for translocation to pancreas, and 62%, 46%, 58% vs 100% for translocation to mesenteric lymph nodes, respectively, P 〈 0.05 for all）. CONCLUSION： The present study confirms the benefit of HBO and allopurinol treatment when administered separately in experimental rat AP. Combination of these treatment options appears to prevent progression of pancreatic injury parameters more effectively.

Effects of retrospective quality control on pressure-flow data with computer-based urodynamic systems from men with benign prostatic hyperplasia

Aim： To evaluate the effects of retrospective quality control on pressure-flow data with computer-based urodynamic systems from men with benign prostatic hyperplasia （BPH）. Methods： A total of 582 traces of pressure-flow study from 181 men with BPH was included in the study. For each trace, maximum urinary flow rate （Qmax） and detrusor pressure at Qmax （pdet.Qmax） were, respectively, read from manually smoothed and corrected uroflow and detrusor pressure curves from the computer print-outs. Obstruction coefficient, International Continence Society （ICS） and Schaefer nomograms were used to detect urethral resistance and to diagnose obstruction. The results obtained by manual reading were compared with those from computer-based systems. Results： After manual correction, Qmax underwent a consistently significant decrease by 1.2 mL/s on average （P 〈 0.001）, and had a change range of 0.5-10.4 mL/s. However, pdet.Qmax underwent inconsistently intra-individual changes after correction. The obstruction coefficient increased significantly, by an average of 0.07 （P 〈 0.05）. Using the ICS nomogram, the percentage of obstruction increased from 69.8% to 73.9%, and of the non-obstruction decreased from 8.8% to 5.3% （P 〈 0.05）. There were 11% of traces that changed the classifications using the ICS nomogram, and 28.9% that changed the grades for the Schaefer nomogram. Conclusion： Systematically significant differences in parameters from pres- sure-flow study between manual readings and computer recordings were demonstrated. Manual correction resulted in a consistently lower Q a higher urethral resistance, and an aggravating obstruction. Manual readings can correct considerable false diagnoses for obstruction. Retrospective quality control of pressure-flow data with com- puter-based systems is necessary.

Self-reported risk of stroke and factors associated with underestimation of stroke risk among older adults with atrial fibrillation: the SAGE-AF study

Background Though engaging patients with atrial fibrillation(AF) in understanding their stroke risk is encouraged by guidelines, little is known regarding AF patients' perceived stroke risk or its relationship with oral anticoagulation(OAC) use. We aim to identify factors associated with underestimation of stroke risk among older patients with AF and relate this to OAC use. Methods Data are from the ongoing SAGE(Systematic Assessment of Geriatric Elements)-AF study, which included older patients(> 65 years) with non-valvular AF and a CHA2 DS2-VASc score of ≥ 2. Participants reported their perceived risk of having a stroke without OAC. We compared the perceived risk to CHA2 DS2-VASc predicted stroke risk and classified participants as "over" or "under" estimators, and identified factors associated with underestimation of risk using multiple logistic regression. Results The average CHA2 DS2-VASc score of 915 participants(average age: 75 years, 47% female, 86% white) was 4.3 ± 1.6, 43% of participants had discordant predicted and self-reported stroke risks. Among the 376 participants at highest risk(CHA2 DS2-VASc score ≥ 5), 46% of participants underestimated their risk. Older participants(≥ 85 years) were more likely and OAC treated patients less likely to underestimate their risk of developing a future stroke than respective comparison groups. Conclusions A significant proportion of study participants misperceived their stroke risk, mostly by overestimating. Almost half of participants at high risk of stroke underestimated their risk, with older patients more likely to do so. Patients on OAC were less likely to underestimate their risk, suggesting that successful efforts to educate patients about their stroke risk may influence treatment choices.

Cognitive and Functional Profiles in Mild-to-Moderate Alzheimer’s Disease and Mild Cognitive Impairment Compared to Healthy Elderly

Background: Amnestic mild cognitive impairment (aMCI) and mild-to-moderate Alzheimer’s disease (AD) are clinically distinct but impact cognitive and functional ability similarly. Comprehensive assessment of cognitive and functional deficits may prove useful in informing differential diagnosis in early stages of dementia and in informing endpoint selection in therapeutic AD trials. Objective: The objective of this study was to characterize patterns of cognitive and functional impairment in aMCI and mild-to-moderate AD subjects compared to cognitively intact healthy elderly (HE). Methods: Thirty-one healthy elderly, 20 aMCI and 19 AD participants were administered a cognitive test battery that included the ADAS-Cog and functional assessments. Z-scores were calculated for all endpoints based on the HE reference group. Results: Cognitive deficits were observed in AD and aMCI participants relative to the referent group. On average, aMCI participants performed 1 - 2 standard deviations below HE on cognitive tests, and AD participants performed 2 - 3 standard deviations below HE. Domain-specific functional deficits among AD participants (z- score -0.4 to -6.4) were consistently greater than those of aMCI participants (z-score 0 to -1.7). Conclusion: This study provides further support for comprehensive assessment and monitoring of cognitive and functional domain scores in the diagnosis and treatment of aMCI and mild AD. Domain-specific cognitive scores may be more useful than composite scores in characterizing impairment and decline. Measuring domains such as attention, processing speed and executive function may increase the sensitivity of detecting disease progression and therapeutic effects, particularly in mild-moderate AD where memory decline may be too slow to detect drug effects during a typical clinical trial.

α-突触核蛋白对小鼠星形胶质细胞的激活作用

目的研究外源性α-突触核蛋白(α-syn)及其A53T突变型对星形胶质细胞的激活作用。方法分离培养小鼠原代星形胶质细胞,经α-syn和A53T刺激后,用实时荧光定量聚合酶链反应和Western blot检测Toll样受体(TLRs)和核转录因子-κB(NF-κB)的表达变化。结果与对照组比较,2种α-syn提高TLRs1~4和NF-κB的表达水平(P<0.05),其中A53T作用更强;Western blot检测结果表明,A53T提高TLR2和NF-κB的蛋白水平。结论α-syn激活星形胶质细胞介导的固有免疫反应,为神经退行性疾病机制提供免疫学证据。

Cross-sectional and longitudinal studies on interaction between bladder compliance and outflow obstruction in men with benign prostatic hyperplasia

Aim： To explore the interaction between bladder compliance （BC） and bladder outflow obstruction （BOO） in men with benign prostatic hyperplasia （BPH） using cross-sectional and longitudinal studies. Methods： A total of 181 men with BPH were recruited, and 100 of them were followed for one year. Cystometry was performed in a standing or a sitting position with 30 mL/min infusion. BC was manually corrected and defined. Obstruction coefficient （OCO）, linear passive urethral resistance relation and international continence society （ICS） nomogram were used to diagnose BOO. The obstructed parameters were compared between the reduced BC group and the non-reduced group. BC was compared between the first investigation at the beginning of study and the second investigation at the end of study during the one-year follow-up period. Results： The group with reduced BC had increased OCO and linear passive urethral resistance relation. BC was significantly lower in the obstructed group （55.7 mL/cm water） than that in unobstructed and equivocal one （74.9 mL/cm water, P 〈 0.01）. BC gradually reduced with the increased obstructed grade. There was a significantly weak negative correlation between BC and OCO （r = - 0.132, P 〈 0.01）. Over the one-year follow-up period in the longitudinal study, BC for all men changed from 54.4 to 48.8 mL/cm water （P 〉 0.05）, and BC for the group with BOO fell from 58.4 ± 70.1 to 46.5 ± 38.7 mL/cm water （P 〉 0.05）. Conclusion： In men with BPH, a significant systematic decrease occurred in BC in the obstructed group and a significant systematic increase with urethral resistance occurred in the low BC group. A longitudinal study of the tendency of BC reduction in a group with BOO is necessary in the future.

年龄对心血管系统的影响(英文)

高龄是发生心血管疾病的一个重要危险因素。很显然,随着老年人吸烟,以及患高血压、糖尿病、血脂异常等儿率的增加,更容易发生心血管疾病。另外有证据显示,即使无其他危险因素,衰老也会引起心血管结构和功能的变化。研究表明,随着时间的推移,衰老的心脏和血管出现了细胞和亚细胞缺陷,更重要的是,即使无明显心血管疾病的人也存在与年龄相关的这些变化,使老年人易患心血管疾病,引起舒张功能障碍和单纯收缩性高血压等常见问题。

Acute coronary syndrome in the older adults

Coronary heart disease remains the leading cause of death in the developed world. Advanced age is the single strongest risk factor for coronary artery disease （CAD） and independent predictor for poor outcomes following an acute coronary syndrome （ACS）. ACS refers to a spectrum of conditions compatible with acute myocardial ischemia and/or infarction due to various degrees of reduction in co- ronary blood flow as a result of plaque rupture/erosion and thrombosis formation or supply and demand mismatch.

Physical activity after total knee arthroplasty: A critical review

Total knee arthroplasty(TKA) is the most commonly performed elective surgery in the United States. TKA typically improves functional performance and reduces pain associated with knee osteoarthritis. Little is known about the influence of TKA on overall physical activity levels. Physical activity, defined as "any bodily movement produced by skeletal muscles that results in energy expenditure", confers many health benefits but typically decreases with endstage osteoarthritis. The purpose of this review is to describe the potential benefits(metabolic, functional, and orthopedic) of physical activity to patients undergoing TKA, present results from recent studies aimed to determine the effect of TKA on physical activity, and discuss potential sources of variability and conflicting results for physical activity outcomes. Several studies utilizing self-reported outcomes indicate that patients perceive themselves to be more physically active after TKA than they were before surgery. Accelerometry-based outcomes indicate that physical activity for patients after TKA remains at or below pre-surgical levels. Several different factors likely contributed to these variable results, including the use of different instruments, duration of follow-up, and characteristics of the subjects studied. Comparison to norms, however, suggests that daily physical activity for patients following TKA may fall short of healthy agematched controls. We propose that further study of the relationship between TKA and physical activity needs to be performed using accelerometry-based outcome measures at multiple post-surgical time points.

Stable ischemic heart disease in the older adults

1 Introduction Ischemic heart disease is caused by atherosclerotic and/or thrombotic obstruction of coronary arteries. Clinical spec- trum of ischemic heart disease expands from asymptomatic atherosclerosis of coronary arteries to acute coronary syn- dromes （ACS） including unstable angina, acute myocardial infarction （non-ST elevation myocardial infarction and ST elevation myocardial infarction）. Stable ischemic heart dis- ease （SIHD） refers to patients with known or suspected SIHD who have no recent or acute changes in their symp- tomatic status, suggesting no active thrombotic process is underway.

Knowledge, Attitudes and Beliefs about Dementia in an Urban Xhosa-Speaking Community in South Africa

Background: Dementia, a debilitating condition, requires particular attention in Southern Africa where there is a dearth of prevalence data. Population ageing and other risk factors are driving an increasing incidence of dementia. However, limited knowledge and understanding may impact the attitudes and practices towards persons with dementia. Aim: To investigate the relationship between the knowledge of dementia, its effect on the attitudes and practices toward people with dementia in an urban community setting. To determine the perceived availability of services for those with dementia, the awareness of elder abuse and care-giver burden. Methods: A descriptive, cross-sectional study was performed in Khayelitsha. An interviewer administered questionnaire was used with assistance from isiXhosa speaking translators. A sample of 100 individuals was surveyed door-to-door from both the informal and formal housing settlements, using cluster random sampling methods. Results: There was deficient knowledge about dementia, with an average accuracy of 53.44% on the knowledge test. Only 10% reported knowing what dementia was. Participants had generally tolerant views about people with dementia. No significant relationship was found between knowledge and attitudes about dementia. There was a significant difference between people who would share their house with a family member with dementia or send them to nursing homes (p = 0.03). 64% of participants knew what elder abuse was. 19% knew of an elder who had been abused;amongst the most common forms reported were being locked alone in their house and being deprived of food. Conclusions: This study showed that knowledge about dementia was limited with no relationship to attitudes of high tolerance towards people with dementia. Elder abuse was well recognized, but poorly reported. Appropriate health promotion strategies and education should be conducted and further research should be done into dementia in South Africa.

ARNI and SGLT2i: a promising association to be used with caution

During the last years, several pharmacological treatments have significantly improved outcome of patients with heart failure with reduced ejection fraction(HFr EF) particularly by inhibiting the renin–angiotensin–aldosterone system(RAAS) and by blocking the sympathetic system.[1,2] More recently, it was demonstrated that a further positive neurohormonal modulation of RAAS and of the natriuretic peptides pathway with Sacubitril/Valsartan(Sa/Va).

Clinical decision support for drug related events: Moving towards better prevention

Clinical decision support(CDS) systems with automated alerts integrated into electronic medical records demonstrate efficacy for detecting medication errors(ME) and adverse drug events(ADEs). Critically ill patients are at increased risk for ME, ADEs and serious negative outcomes related to these events. Capitalizing on CDS to detect ME and prevent adverse drug related events has the potential to improve patient outcomes. The key to an effective medication safety surveillance system incorporating CDS is advancing the signals for alerts by using trajectory analyses to predict clinical events, instead of waiting for these events to occur. Additionally, incorporating cutting-edge biomarkers into alert knowledge in an effort to identify the need to adjust medication therapy portending harm will advance the current state of CDS. CDS can be taken a step further to identify drug related physiological events, which are less commonly included in surveillance systems. Predictive models for adverse events that combine patient factors with laboratory values and biomarkers are being established and these models can be the foundation for individualized CDS alerts to prevent impending ADEs.

Clinical pharmacology relevant to older adults with cardiovascular disease

1 Introduction Although older adults are generally among the highest users of cardiovascular medications, they are typically underrepresented or excluded from most efficacy and safety trials. Drug developers are usually reluctant to include many senior adults in randomized controlled clinical trials in part due to their high prevalence of multiple comorbidities, frailty, and polypharmacy; and to age-related pharmacokinetic and pharmacodynamic complexities. Consequently, there is often insufficient high quality evidence-based data to inform pharmacologic management of common cardiovascular conditions on older adults. In the absence of data, clinicians often rely on conceptual principles regarding metabolism and drug-drug interactions to minimize adverse drug events, but this is often not well-substantiated or standardized. A related challenge is poor cardiovascular medication adherence among older adults, and its detrimental impact on their health outcomes. In this brief review we highlight some aspects of these topics.

Acute heart failure in the elderly:setting related differences in clinical features and management

BACKGROUND Administrative data show that acute heart failure(HF)patients are older than those enrolled in clinical registries and frequently admitted to non-cardiological settings of care.The purpose of this study was to describe clinical characteristics of old patients hospitalised for acute HF in Cardiology,Internal Medicine or Geriatrics wards.METHODS Data came from ATHENA(AcuTe Heart failurE in advaNced Age)registry which included elderly patients(≥65 years)admitted to the above mentioned settings of care from December 1,2014 to December 1,2015.RESULTS We enrolled 396 patients,15.4%assigned to Cardiology,69.7%to Internal Medicine,and 14.9%to a Geriatrics ward.Mean age was 83.5±7.6 years(51.8%of patients≥85 years)and was higher in patients admitted to Geriatrics(P<0.001);more than half were females.Medical treatments did not differ significantly among settings of care(in a context of a low prescription rate of renin-angiotensin-aldosterone system inhibitors)whereas significant differences were observed in comorbidity patterns and management guidelines recommendation adherence for decongestion evaluation with comparison of weight and N-terminal pro-B-type natriuretic peptide levels on admission and at discharge(both P=0.035 and P<0.001),echocardiographic evaluation(P<0.001)and follow-up visits planning(P<0.001),all higher in Cardiology.Mean in-hospital length of stay was 9±5.9 days,significantly higher in Geriatrics(13.7±6.5 days)and Cardiology(9.9±6.7 days)compared to Internal Medicine(8±5.2 days),P<0.001.In-hospital mortality was 9.3%,resulting higher in Geriatrics(18.6%)and Cardiology(16.4%)than Internal Medicine(5.8%),P=0.001.CONCLUSIONS In elderly patients hospitalised for acute HF,clinical characteristics and management differ significantly according to the setting of admission.