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.

Vascular depression for radiology: A review of the construct,methodology,and diagnosis

Vascular depression(VD)as defined by magnetic resonance imaging(MRI)has been proposed as a unique subtype of late-life depression.The VD hypothesis posits that cerebrovascular disease,as characterized by the presence of MRIdefined white matter hyperintensities,contributes to and increases the risk for depression in older adults.VD is also accompanied by cognitive impairment and poor antidepressant treatment response.The VD diagnosis relies on MRI findings and yet this clinical entity is largely unfamiliar to neuroradiologists and is rarely,if ever,discussed in radiology journals.The primary purpose of this review is to introduce the MRI-defined VD construct to the neuroradiology community.Case reports are highlighted in order to illustrate the profile of VD in terms of radiological,clinical,and neuropsychological findings.A secondary purpose is to elucidate and elaborate on the measurement of cerebrovascular disease through visual rating scales and semi-and fully-automated volumetric methods.These methods are crucial for determining whether lesion burden or lesion severity is the dominant pathological contributor to VD.Additionally,these rating methods have implications for the growing field of computer assisted diagnosis.Since VD has been found to have a profile that is distinct from other types of late-life depression,neuroradiologists,in conjunction with psychiatrists and psychologists,should consider VD in diagnosis and treatment planning.

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.

Depression among caregivers of patients with dementia:Associative factors and management approaches

As elderly people increasingly come to represent a higher proportion of the world’s population,various forms of dementia are becoming a significant chronic disease burden.The World Health Organization emphasizes dementia care as a public health priority and calls for more support for family caregivers who commonly play a significant,central role in dementia care.Taking care of someone with dementia is a long-term responsibility that can be stressful and may lead to depression among family caregivers.Depression and related behavioral and cognitive changes among caregivers could in turn affect the status and prognosis of the dementia patient.This review article explores depression in dementia caregivers and summarizes proposed mechanisms,associated factors,management and research findings,and proposes future research directions.

Synchronous primary carcinomas of the bladder and prostate

Aim： To determine the incidence of adenocarcinoma of the prostate for patients undergoing radical cystoprostatectomy for bladder cancer in Taiwan. Methods： A total of 248 patients in Taiwan who were histologically confirmed for transitional cell carcinoma of the bladder underwent cystoprostatectomy. Histopathologic evaluation of the prostate specimens sectioned at 5 mm intervals was performed. Results： Of the 248 patients, 10 （4.03%） were found to have prostate cancer. Of the 10 cases of unsuspected prostate cancer, eight proved to be at stage T1 or T2, and two at T3 and T4, respectively. This rate of incidentally found prostate cancer amongst our bladder cancer patients appeared to be lower than that found in bladder cancer patients in similar studies in USA. Conclusion： Although the incidence of incidental prostate cancer in patients in Taiwan with bladder cancer is not high compared with that in Western countries, we suggest that digital rectal examination and prostate-specific antigen （PSA） are important screening tools for men with bladder cancer, especially for those aged 60 years and older in Taiwan.

Metabolic syndrome and its association with components of sarcopenia in older community-dwelling Chinese

Aging and obesity contribute to muscle dysfunction. This study aimed to determine the cross-sectional associations between components of metabolic syndrome (MetS) and sarcopenia in 251 older community- dwelling Chinese. The total fat-free mass was measured by dual-energy X-ray absorptiometry, muscle strength (handgrip strength) by a handheld dynamometer, physical performance by 4-meter walk, 5-time chair stand test, and the short physical performance battery (SPPB). MetS was defined using the International Diabetes Federation (IDF) criteria. The participants with MetS had a higher appendicular skeletal muscle mass (ASM) and relative ASM (RASM). The males with MetS had higher handgrip strength, and the females with MetS had higher SPPB scores. After adjusting for age and body mass index, the participants with an increased waist circumference had a higher ASM, and those with increased diastolic blood pressure (DBP) also had higher handgrip strength. The males with elevated fasting blood glucose (FBG) levels had a lower gait speed. Components of MetS, such as DPB and FBG, were associated with muscle strength and physical performance in older adults. These results suggest that muscle strength and function should be considered in treating older adults with MetS.

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.

Geriatric assessment for oncologists

The world is experiencing aging of its population. Age-specific incidence rates of cancer are higher and cancer is now recognized as a part of aging. Treating older patients can be challenging. The clinical behavior of some tumors changes with age and the aging process itself brings physiological changes leading to decline in the function of organs. It is essential to identify those patients with longer life expectancy, potentially more likely to benefit from aggressive treatment vs. those that are more vulnerable to adverse outcomes. A primary determination when considering therapy for an older cancer patient is a patient's physiologic, rather than chronologic age. In order to differentiate amongst patients of the same age, it is useful to determine if a patient is fit or frail. Frail older adults have multiple chronic conditions and difficulties maintaining independence. They may be more vulnerable to therapy toxicities, and may not have substantial lasting benefits from therapy. Geriatric assessment(GA) may be used as a tool to determine reversible deficits and devise treatment strategies to mitigate such deficits. GA is also used in treatment decision making by clinicians, helping to risk stratify patients prior to potentially high-risk therapy. An important practical aspect of GA is the feasibility of incorporating it into a busy oncology practice. Key considerations in performing the GA include: available resources, patient population, GA tools to use, and who will be responsible for using the GA results and develop care plans. Challenges in implementing GA in clinical practice will be discussed.

Relation of Indices of Lung Hyperinflation to Dyspnea in Patients with Chronic Obstructive Pulmonary Disease: A Physiologic Assessment and Discussion

Background: The severity of COPD is commonly assessed by the reduction in forced expiratory volume at one second (FEV1), although more recently prognostic factors influencing survival have also incorporated functional capacity, degree of breathlessness on exertion, and body mass index. Increasingly, the reliability of physiological parameters such as FEV1 to predict patient-centered outcomes has been brought into question. Objectives: To evaluate the relationship between dyspnea as assessed by the Modified Medical Council Dyspnea (MMRC) scale, the Global Initiative for Chronic Obstructive Lung Disease (GOLD 2014) staging and indices of lung hyperinflation and spirometry. Methods: Data were retrospectively analyzed at a 600-bed tertiary care center including spirometry, plethysmographic lung volumes, single breath carbon monoxide diffusion capacity and dyspnea graded according to MMRC, and GOLD staging. Results: Data for 331 patients were analyzed. Differences amongst FEV1, IC, IC/TLC, FRC and RV/TLC were significant between GOLD I/II and GOLD III/IV groups. The closest relationship to GOLD staging was seen with FEV1, FVC and slow vital capacity (SVC). FEV1/FVC, IC, and IC/TLC were inversely associated with MMRC score, while RV/TLC exhibited a positive relation with MMRC score. Conclusions: Indices of lung hyperinflation are closely associated, with dyspnea as assessed by MMRC grading with TLC, RV/TLC and IC exhibiting the closest relations, more so than FEV1. GOLD staging also shows strong correlations with lung volume subdivisions (weakly with TLC), more so than with FEV1. That TLC changed little between GOLD stages can be explained by the presence of collateral interalveolar channels and population characteristics different from those of other studies. These findings further support the concept that more than a reduction in FEV1, lung hyperinflation contributes to the sensation of dyspnea in airflow limitation.

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.

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).