Prevalence and clinical implications of polypharmacy and potentially inappropriate medication in elderly patients with heart failure: results of six months' follow-up / 老年心脏病学杂志（英文版）

OBJECTIVES@#To investigate the prevalence of polypharmacy and potentially inappropriate medication (PIM) in elderly patients with heart failure (HF) and their impact on readmission and mortality.@*METHODS@#We conducted a study of 274 participants aged 60 years or older with HF. The prevalence of polypharmacy (defined as the use of five or more medications) was calculated, and the 2019 American Geriatrics Society Beers criteria were applied to access PIMs. Medications and PIMs were characterized at admission and discharge, and changes in prescriptions during hospitalization were compared. The impact of polypharmacy and PIM on readmission and mortality were investigated.@*RESULTS@#The median age of this study population was 68 years old. The median number of prescribed drugs was 7 at admission and 10 at discharge. At discharge, 99.27% of all patients were taking five or more drugs. The incidence of composite endpoint and cardiovascular readmission increased with the number of polypharmacy within 6 months. The use of guideline-directed medical therapy reduced the incidence of composite endpoint events and cardiovascular readmission, while the use of non-cardiovascular medications increased the composite endpoint events. The frequency of PIMs was 93.79% at discharge. The incidence of composite endpoint events increased with the number of PIMs. "PIMs in older adults with caution" increased cardiovascular readmission and "PIMs based on kidney function" increased cardiovascular mortality. Several comorbidities were associated with cardiovascular mortality or non-cardiovascular readmission.@*CONCLUSIONS@#Polypharmacy and PIM were highly prevalent in elderly patients with HF, and their use was associated with an increased risk of composite endpoint events, readmission and mortality. Non-cardiovascular medications, "PIMs in older adults with caution", "PIMs based on kidney function" and several comorbidities were important factors associated with hospital readmission and mortality. Our findings highlight the importance of medication optimization in the management of HF in elderly patients.

Effects of phlorizin on vascular complications in diabetes db/db mice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Diabetic macrovascular complications are important causes of cardiovascular and cerebrovascular diseases and also one of the major causes of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Phlorizin has been reported to be effective in reducing the blood glucose level in diabetic mellitus, while little is known about its effects on vascular complications. This study aimed to observe the effects of phlorizin on the aorta of diabetes db/db mice and explore its mechanism.</p><p><b>METHODS</b>Diabetic db/db mice (n = 16) and age-matched db/m mice (n = 8) were divided into three groups: normal control group (CC group, db/m mice, n = 8), untreated diabetic group (DM group, db/db mice, n = 8) and diabetic group treated by phlorizin (DMT group, db/db mice, n = 8). Phlorizin (20 mg/kg body weight) was given in normal saline solution intragastrically for 10 weeks. Animals were weighed weekly. At the 10th weekend, all mice were fasted overnight and then sacrificed. Fasting blood was collected, and the aortas were dissected. The blood samples were analyzed for fasting blood glucose (FBG), serum advanced glycation end products (AGEs), malondialdehyde (MDA) and superoxide dismutase (SOD) activity, the aortic ultrastructure was studied.</p><p><b>RESULTS</b>The weight and serum concentration of FBG, AGEs, and MDA in the DM group were higher than that in the CC group (P < 0.01), and they were significantly lower in the DMT group (P < 0.05). Serum SOD activity was lower than that in the CC group (P < 0.01), and it is significantly higher in the DMT group (P < 0.05). The severity of aorta damage in the DMT group was less than that in the DM group.</p><p><b>CONCLUSIONS</b>Phlorizin protected the db/db mice from diabetic macrovascular complications, attributed to the decreasing of blood glucose and AGEs level, and its antioxidant potential. This study may provide a new natural medicine for treating diabetic macrovascular complications.</p>

Determination of L-tetrahydropalmatine in human plasma by HPLC and pharmacokinetics of its disintegrating tablets in healthy Chinese.

The objective of the study was to establish an HPLC method for the determination of L: -tetrahydropalmatine in human plasma, and to investigate the pharmacokinetics after oral administration of L: -tetrahydropalmatine disintegrating tablets in healthy Chinese. L: -tetrahydropalmatine in human plasma was separated on a Phenomenex luna C(18) column (250 mm × 4.6 mm, 5 µm), eluted using methanol-water (75:25, v/v) as mobile phase, and detected by photodiode array detector at a wavelength of 281 nm. A single 60 mg of L: -tetrahydropalmatine orally disintegrating tablets were orally given to 12 healthy male volunteers after fasting overnight. Before and after administration 4 mL of blood samples was collected at the scheduled time. The plasma concentration of L: -tetrahydropalmatine was determined by the established HPLC method after disposition and its pharmacokinetic parameters were analyzed and evaluated by both compartmental and noncompartmental models using Drug and Statistic (version 2.0). The disintegrating time and the sense of mouth were observed and recorded. The lowest limit of quantification (LLOQ) for L: -tetrahydropalmatine in plasma was 0.01 µg mL(-1), and a linearity was obtained in the range of 0.01-1 µg mL(-1) (r = 0.9998). The disposal procedure of L: -tetrahydropalmatine in human was fitted using the DAS program, following a double-compartment open model system (w = 1). L: -tetrahydropalmatine was absorbed quickly with t (1/2ka) of 0.5 ± 0.054 h, distributed fast with t (1/2α) of 0.74 ± 0.088 h, and eliminated slowly with t (1/2ß) of 11.42 ± 2.43 h. L: -tetrahydropalmatine was distributed mainly in the periphery compartment with the V(1)/F of 133.30 ± 30.78 L. L: -tetrahydropalmatine orally disintegrating tablets with good taste were disintegrated in the mouth within 16 s. The established HPLC method was sensitive, rapid, and suitable for both L: -tetrahydropalmatine pharmacokinetic studies and its content assay in traditional Chinese medicine (TCM). The procedure of L: -tetrahydropalmatine in human was fit to double-compartmental model (w = 1). L: -tetrahydropalmatine orally disintegrating tablets were palatable, well-tolerated, disintegrated and absorbed quickly.

Comparison of adenosine stress and dobutamine stress by real-time myocardial contrast echocardiography in detecting myocardium ischemia in dogs / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Real-time perfusion imaging (RTPI) using ultrasound contrast agents has shown good "accuracy" in detecting myocardial infarction, however its accuracy in the assessment of peri-infarct ischemia and stress echocardiography are not known. The aim of this study was to determine the accuracy of RTPI in assessment of peri-infarct ischemia during dobutamine and adenosine stress.</p><p><b>METHODS</b>We employed the RTPI modality (Agilent and ATL Philips) in a canine model (18 dogs) of distal coronary occlusion and proximal coronary stenosis. Using coronary flow probe recordings, the physiologic significance of proximal coronary stenosis was established by confirming abolition of the coronary reserve. The contrast agent Optison was given as a slow bolus injection at baseline, during prolonged distal coronary occlusion, during adenosine bolus stress and during dobutamine stress. Triphenyltetrazolium chloride (TTC) staining was used to verify a distal infarction. RTPI recordings at baseline, the distal coronary occlusion and stress protocols were randomly mixed and reviewed blindly.</p><p><b>RESULTS</b>In all but one dog, RTPI detected a distal infarct as small as 9% of the left ventricle. The sensitivity, specificity and overall diagnostic accuracy of RTPI in the detection of distal infarcts were: 94%, 89% and 92%, respectively. The sensitivity, specificity, and overall diagnostic accuracy of RTPI in the assessment of peri-infarction ischemia were 83%, 92% and 88% for adenosine stress and 95%, 86% and 91% for dobutamine stress, respectively.</p><p><b>CONCLUSIONS</b>Even small distal infarcts can be detected by RTPI; peri-infarct ischemia can be accurately recognized by RTPI during stress; adenosine and dobutamine stress appear equally reliable in the RTPI evaluation of peri-infarct ischemia.</p>

Activation of sterol regulatory element binding protein and its involvement in endothelial cell migration / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the activation of sterol regulatory element binding protein (SREBP) and its critical role in endothelial cell migration.</p><p><b>METHODS</b>Bovine aortic endothelial cells (ECs) were cultured. The expression of SREBP and Cdc42 were determined by Western blot and quantitative real-time PCR. Moreover, outward growth migration model and transwell chamber assay were used to detect ECs migration.</p><p><b>RESULTS</b>(1) SREBP was activated during ECs migration. Western blot analysis demonstrated increased active form SREBP in migrating as compared to non-migrating ECs population. SREBP activation decreased as ECs migration slowed;(2) Coincidental with SREBP activation, mRNA expression of its target genes such as low density lipoprotein receptor, HMG-CoA reductase, and fatty acid synthase also increased in migrating ECs population as detected by real-time PCR; (3) Migration induced SREBP activation in ECs was inhibited by SREBP-acting protein RNAi and pharmacologically by 25-hydroxycholesterol; (4) Inhibition of SREBP led to decreased ECs migration in various models; (5) Cells genetically deficient in SREBP-acting protein, S1P, or S2P, phenotypically exhibited impaired migration; (6) SREBP inhibition in ECs suppressed the activity of small GTPase Cdc42, a key molecule for ECs motility.</p><p><b>CONCLUSIONS</b>SREBP is activated during and plays a critical role in ECs migration. Targeting SREBP could become a novel approach in fighting diseases involving abnormal ECs migration.</p>

A novel approach of proteomics to study the mechanism of action of grape seed proanthocyanidin extracts on diabetic retinopathy in rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Diabetic retinopathy (DR) is a leading cause of visual impairment and blindness among the people of occupational age. To prevent the progress of retina injury, effective therapies directed toward the key molecular target are required. Grape seed proanthocyanidin extracts (GSPE) have been reported to be effective in treating diabetic complications, while little is discussed about the functional protein changes.</p><p><b>METHODS</b>We used streptozotocin (STZ) to induce diabetes in rats. GSPE (250 mg/kg body weight per day) were administrated to diabetic rats for 24 weeks. Serum glucose, glycated hemoglobin and advanced glycation end products (AGEs) were determined. Consequently, 2-D difference gel electrophoresis and mass spectrometry were used to investigate retina protein profiles among control, STZ-induced diabetic rats, and GSPE treated diabetic rats.</p><p><b>RESULTS</b>GSPE significantly reduced the AGEs of diabetic rats (P < 0.05). Moreover, GSPE significantly suppressed the vascular lesions of central regions, decreased capillary enlargements and neovascularization, similar to those of the control rats under light microscope. Eighteen proteins were found either up-regulated or down-regulated in the retina of STZ-induced diabetic rats. And seven proteins in the retina of diabetic rats were found to be back-regulated to normal levels after GSPE therapy. These back-regulated proteins are involved in many important biological processes such as heat shock, ubiquitin-proteasome system, cell proliferation, cell growth and glucose metabolism.</p><p><b>CONCLUSIONS</b>These findings might promote a better understanding for the mechanism of DR, and provide novel targets for evaluating the effects of GSPE therapy.</p>

Anti-tumor effects of polybutylcyanoacrylate nanoparticles of diallyl trisulfide on orthotopic transplantation tumor model of hepatocellular carcinoma in BALB/c nude mice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Hepatocellular carcinoma (HCC) ranked the second among the causes of cancer mortality in China since the 1990s. Up to now, medication still plays an important role in the treatment of HCC. The therapies based on the allicin as a potential chemopreventive analog although is in its infancy at the present time, may have a significant role in the future management of HCC. Diallyl trisulfide (DATS) is a natural compound derived from garlic. In this study, we investigated the inhibitory effects of hepatic targeted polybutylcyanoacrylate nanoparticles of diallyl trisulfide (DATS-PBCA-NP) on orthotopic transplanted HepG2 hepatocellular carcinoma in nude mice.</p><p><b>METHODS</b>DATS-PBCA-NP were detected by transmission electron microscope (TEM) and high-performance liquid chromatography (HPLC). The orthotopic transplantation HCC models were established by implanting HCC HepG2 xenograft bits under the envelope of the mice liver. Successful models (n = 29) were divided into 4 groups: normal saline (NS), empty nanoparticles (EN), DATS and DATS-PBCA-NP were intravenously administered to the mice respectively for 2 weeks. In vivo antitumor efficacy was evaluated by the measurement of tumor volume. Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) assay and protein levels of apoptosis and cell proliferation proteins by immunoblotting in tumor tissues were performed to elucidate the possible mechanism.</p><p><b>RESULTS</b>DATS-PBCA-NP possessed smooth and round appearance, dispersed well, and released in vitro in accord with double phase kinetics model. DATS-PBCA-NP changed the tissue/organ distribution of DATS in vivo. The successful rate of tumor implantation was 100%. Intravenous administration of DATS-PBCA-NP significantly retarded the growth of orthotopically transplanted hepatoma in BALB/c nude mice (compared with the other three groups, all P < 0.05) without causing weight loss (P > 0.05). TUNEL staining showed that the tumors from DATS-PBCA-NP treated mice exhibited a markedly higher apoptotic index compared with control tumors. Western blot analysis of tumor tissue revealed that the down-regulated expression of proliferation cell nuclear antigen (PCNA) and Bcl-2 proteins in DATS-PBCA-NP group, and there were no significant differences in the expression of Fas, FasL and Bax proteins among the four groups (P > 0.05).</p><p><b>CONCLUSIONS</b>DATS-PBCA-NP has good prolonged release effect in vivo and hepatic-targeted activity, and significant anti-tumor effect on the orthotopic transplantation HCC model in mice in association with the suppression of proliferation and the induction of apoptosis of tumor cells. These advantages are probably due to their liver targeting characteristics and consequently bring a higher anti-tumor activity.</p>

Comparison of the veracity of real-time perfusion, harmonic angio, and ultraharmonic mocardial contrast imaging modes in evaluation of acute myocardial infarction area / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Innovative advancements in ultrasound instrumentation present a number of imaging modalities for myocardial contrast echocardiography (MCE) in ischemic syndromes. How well they compare to each other in diagnostic accuracy in the detection of acute myocardial infarction is unclear. The purpose of this study was to assess the relative accuracy of 3 different imaging modes of MCE, low mechanical index (MI) real-time perfusion imaging (RTPI), triggered harmonic angio mode (HA), and ultraharmonic imaging mode (UH) in the detection of acute experimental myocardial infarction within the time frame suitable for potential reperfusion.</p><p><b>METHODS</b>MCE was performed in 10 open-chest dogs using RTPI, triggered HA and triggered UH modes at baseline and one hour after occlusion of left anterior descending coronary artery. Presence or absence of perfusion defects, and the perfusion defect size when present, were analyzed and compared with the infarct size delineated by triphenyltetrazolium chloride (TTC) staining.</p><p><b>RESULTS</b>The infarct area was (15.8 +/- 2.4)% by TTC staining; Perfusion defect area by MCE was similar to anatomic infarct area in all the three MCE approaches: (16.1 +/- 2.7)% by RTPI mode, (15.5 +/- 2.9)% by HA mode, and (15.5 +/- 3.0)% by UH mode. The sensitivity, specificity and overall diagnostic accuracy in the detection of myocardial infarction were 100%, 88%, and 94% for RTPI mode, 88%, 100%, and 94% for HA mode, and 100%, 75%, and 88% for UH mode.</p><p><b>CONCLUSION</b>All modes of MCE, RTPI, triggered HA mode and triggered UH mode have excellent diagnostic accuracy in the immediate hour of acute coronary occlusion within the optimal time frame suitable for reperfusion therapy.</p>

Determination of the aortic pulse wave velocity in 545 healthy subjects / 中华流行病学杂志

<p><b>OBJECTIVE</b>To understand the aortic pulse wave velocity (PWV) in mid-aged and elderly populations and to study the correlation between gender and PWV and the tendency of PWV on different age groups.</p><p><b>METHODS</b>According to the clinical trial guideline, we selected 545 healthy subjects (age, 31-85 years, 395 men and 150 women), and measured carotid-femoral PWV, using Complior.</p><p><b>RESULTS</b>The average value of PWV in Chinese healthy subjects was 11.62 +/- 2.97 m/s. There was no significant difference in the PWV values between males and females who were older than 40 years, but the values of PWV were lower in females than in males in the 30-39 year-old group. PWV was positively correlated with age. In the present study, the reference values of PWV were established in the different age groups, based on the regression equations between PWV and age.</p><p><b>CONCLUSION</b>Aortic pulse wave velocity seemed to be influenced by age but hardly influenced by gender in healthy subjects, so that the reference value of PWV should be established according to the different age groups. When aorta got stiffer, the value PWV got larger accordingly when age was increasing.</p>

Clinical study of the distensibility of large arteries in elderly patients with essential hypertension / 中华流行病学杂志

<p><b>OBJECTIVE</b>To explore the change in the distensibility of large arteries and its influencing factors in elderly patients with essential hypertension.</p><p><b>METHODS</b>Automatic measuring system for pulse wave velocity (PWV) was applied to examine carotid-femoral PWV as an index reflecting distensibility of large arteries. 118 hypertensive patients aged 64 - 83 (mean age 67.12 +/- 10.26) years were included in the study. Of them, 87 were males and 31 were females.</p><p><b>RESULTS</b>PWV of 118 hypertensive patients increased with increasing age (P < 0.001). Multivariate regressive analysis demonstrated that age and systolic blood pressure had the close relationship with PWV (P < 0.001).</p><p><b>CONCLUSION</b>Hypertension of the elderly could cause reduction of distensibility of large arteries. Age and systolic blood pressure had the close relationship with distensibility of large arteries in elderly patients with essential hypertension.</p>