Improved outcome with standardized plan for clinical management of acute decompensated chronic heart failure

Background Our overall goal is to improve clinical care for inpatients with chronic heart failure(CHF).A retrospective assessment of CHF patients admitted to our hospital over the past decade(2005 vs.2014)indicated a need for better strategies to evaluate clinical treatment,implement best practices and achieve optimal patient outcome.To that purpose,we developed a standardized plan to improve in-hospital treatment of acute decompensated CHF patients.Methods&Results Retrospective chart reviews were conducted to compare three cohorts of CHF patients admitted to the University Hospital of Lund at different time points over a 12-year period:2005(365 patients),2014(172 patients)and 2017-2018(57 patients).Little improvement was seen between 2005 and 2014 with respect to one-year mortality(35%vs.34%)and adequate treatment with recommended medications,e.g.,use of renin-angiotensin system blockers(45%vs.51%).A standardized treatment plan was devised to improve outcomes.A third cohort,treated under the plan(2017-2018),was compared with the 2014 cohort.One-year mortality(18%vs.34%)and 30-day readmission(5%vs.30%)were dramatically decreased,and adherence to medication guidelines was achieved.Key elements of the plan included well-defined treatment procedures,enhanced communication and teamwork,education,adequate time for treatment(5 days)and post-discharge follow-up as necessary.Natriuretic peptide(NT-proBNP)levels were useful for assessing patient status,prognosis and response to treatment.Conclusion Developmeof a standard plan for clinical management of acute decompensated CHF patients resulted in significant improvements in patient outcome,as reflected in decreased rates of 30-day readmission and one-year mortality.

Role of Helicobacter pylori infection on nutrition and metabolism

Helicobacter pylori(H. pylori) is a gram-negative pathogen that is widespread all over the world, infecting more than 50% of the world's population. It is etiologically associated with non-atrophic and atrophic gastritis, peptic ulcer and shows a deep association with primary gastric B-cell lymphoma and gastric adenocarcinoma. Recently, the medical research focused on the modification of the gastric environment induced by H. pylori infection, possibly affecting the absorption of nutrients and drugs as well as the production of hormones strongly implicated in the regulation of appetite and growth. Interestingly, the absorption of iron and vitamin B12 is impaired by H. pylori infection, while infected subjects have lower basal and fasting serum levels of ghrelin and higher concentration of leptin compared to controls. Since leptin is an anorexigenic hormone, and ghrelin stimulates powerfully the release of growth hormone in humans, H. pylori infection may finally induce growth retardation if acquired very early in the childhood and in malnourished children. This review is focused on the nutritional effects of H. pylori infection, such as the reduced bioavailability or the malabsorbption of essential nutrients, and of gastrointestinal hormones, as well as on the relationship between H. pylori and the metabolic syndrome.

Increasing angiotensin-converting enzyme(ACE)2/ACE axes ratio alleviates early pulmonary vascular remodeling in a porcine model of acute pulmonary embolism with cardiac arrest

BACKGROUND:Acute pulmonary embolism(APE)with cardiac arrest(CA)is characterized by high mortality in emergency due to pulmonary arterial hypertension(PAH).This study aims to determine whether early pulmonary artery remodeling occurs in PAH caused by massive APE with CA and the protective effects of increasing angiotensin-converting enzyme(ACE)2-angiotensin(Ang)(1-7)-Mas receptor axis and ACE-Ang II-Ang II type 1 receptor(AT1)axis(ACE2/ACE axes)ratio on pulmonary artery lesion after return of spontaneous circulation(ROSC).METHODS:To establish a porcine massive APE with CA model,autologous thrombus was injected into the external jugular vein until mean arterial pressure dropped below 30 mmHg(1 mmHg=0.133 kPa).Cardiopulmonary resuscitation and thrombolysis were delivered to regain spontaneous circulation.Pigs were divided into four groups of five pigs each:control group,APE-CA group,ROSC-saline group,and ROSC-captopril group,to examine the endothelial pathological changes and expression of ACE2/ACE axes in pulmonary artery with or without captopril.RESULTS:Histological analysis of samples from the APE-CA and ROSC-saline groups showed that pulmonary arterioles were almost completely occluded by accumulated endothelial cells.Western blotting analysis revealed a decrease in the pulmonary arterial ACE2/ACE axes ratio and increases in angiopoietin-2/angiopoietin-1 ratio and expression of vascular endothelial growth factor(VEGF)in the APE-CA group compared with the control group.Captopril significantly suppressed the activation of angiopoietin-2/angiopoietin-1 and VEGF in plexiform lesions formed by proliferative endothelial cells after ROSC.Captopril also alleviated endothelial cell apoptosis by increasing the B-cell lymphoma-2(Bcl-2)/Bcl-2-associated X(Bax)ratio and decreasing cleaved caspase-3 expression.CONCLUSION:Increasing the ACE2/ACE axes ratio may ameliorate pulmonary arterial remodeling by inhibiting the apoptosis and proliferation of endothelial cells after ROSC induced by APE.

Function of the CaMKII-ryanodine receptor signaling pathway in rabbits with left ventricular hypertrophy and triggered ventricular arrhythmia

BACKGROUND:Calcium calmodulin-dependent kinase II(CaMKII) can be more active in patients with left ventricular hypertrophy(LVH),which in turn causes phosphorylation of ryanodine receptors,resulting in inactivation and the instability of intracellular calcium homeostasis.The present study aimed to determine the effect of CaMKII-ryanodine receptor pathway signaling in rabbits with left ventricular hypertrophy and triggered ventricular arrhythmia.METHODS:Forty New Zealand rabbits were randomized into four groups(10 per group):sham group,LVH group,KN-93 group(LVH+KN-93),and ryanodine group(LVH+ryanodine).Rabbits in the LVH,KN-93,and ryanodine groups were used to establish a left ventricular hypertrophy model by the coarctation of the abdominal aorta,while those in the sham group did not undergo the coarctation.After eight weeks,action potentials(APs) were recorded simultaneously in the endocardium and epicardium,and a transmural electrocardiogram(ECG) was also recorded in the rabbit left ventricular wedge model.Drugs were administered to the animals in the KN-93 and ryanodine groups,and the frequency of triggered APs and ventricular tachycardia was recorded after the rabbits were given isoprenaline(1 μmol/L) and high-frequency stimulation.RESULTS:The frequency(animals/group) of triggered APs was 0/10 in the sham group,10/10 in the LVH group,4/10 in the KN-93 group,and 1/10 in the ryanodine group.The frequencies of ventricular tachycardia were 0/10,9/10,3/10,and 1/10,respectively.The frequencies of polymorphic ventricular tachycardia or ventricular fibrillation were 0/10,7/10,2/10,and 1/10,respectively.The frequencies of triggered ventricular arrhythmias in the KN-93 and ryanodine groups were much lower than those in the LVH group(P<0.05).CONCLUSIONS:KN-93 and ryanodine can effectively reduce the occurrence of triggered ventricular arrhythmia in rabbits with LVH.The CaMKII-ryanodine signaling pathway can be used as a new means of treating ventricular arrhythmia.

Increased mortality in elderly heart failure patients receiving infusion of furosemide compared to elderly heart failure patients receiving bolus injection

Heart failure(HF)is a condition of cardiac dysfunction and fluid overload.Neurohormonal activation via the reninangiotensin-aldosterone system and the sympathetic nervous system are the pathophysiological cornerstones.[1]Furthermore,HF is a disorder widely associated with grave adverse outcomes and poor prognosis.[2]A loop diuretic is the fundamental drug used to prevent multiorgan failure and improve symptoms in these patients.[3]

Bioreactance and Apelin in the Management of Severe Hyponatremia

Hyponatremia is a severe electrolyte disturbance associated with substantial morbidity and mortality. It often poses a diagnostic and therapeutic challenge. Accurate assessment of patient fluid-volume status is central to effective management. This pilot study aimed to evaluate the usefulness of the Cheetah NICOM bioreactance system and apelin in early differentiation between hypo- and euvolemia in patients with severe hyponatremia. Methods: Patients > 50 years of age with a serum sodium ≤ 125 mmol/L were eligible for inclusion after written informed consent. Blood- and urine analyses of cardiovascular load (NT-proBNP), osmotic stress (copeptin, apelin, osmolality, sodium), mineralocorticoid status (aldosterone, renin) and sympathetic activity (methoxycathecholamines) were analysed at baseline and after isotonic sodium chloride infusion. Bedside bioreactance examination was used to visualise parameters, including stroke volume before and after passive leg raise test. Classification of volume status was made retrospectively blinded for biomarker and bioreactance results. Results: 8 patients (4 hypovolemic and 4 euvolemic), 79 years old, median plasma sodium 120 mmol/L were included. At the Emergency Department volume status was misclassified in all hypo- and in 2 of 4 euvolemic patients. Apelin was significantly higher in hypovolemic patients ((299 vs. 175 ng/ml), p = 0.021). All hypovolemic, but none of the euvolemic, patients had a level above 250 ng/ml. Copeptin did not differ between groups. All patients in the hypovolemic group increased their stroke volume after passive leg raise. Conclusions: Apelin seems to be a promising future biomarker in the early management of severe hyponatremia. Bioreactance measurements may offer a supplement to bedside evaluation of volume status.

Brain natriuretic peptide is a potent vasodilator in aged human microcircula- tion and shows a blunted response in heart failure patients

BackgroundBrain natriuretic 肽(BNP ) 在在发行量的底层是通常在场的，但是它在心失败题目(CHF ) 与拥挤的度同时被提高。BNP 有 natriuretic 效果并且是有势力血管扩张药。BNP 能是在 CHF 的一种治疗学的选择，这被建议。然而，我们要求了在 CHF 的传播 BNP 的高水平可以 downregulate microvascular natriuretic 受体的反应。这被比较 15 个 CHF 病人测试(BNP &#x0003e；3000 ng/L ) 与 10 匹配的、健康 controls.MethodsCutaneous microvascular 血，在前臂的流动被激光 Doppler Flowmetry 测量。本地加热(+44 &#x000b0； C， 10 min ) 被用来唤起一个最大的本地扩张器 BNP 或醋胆素(ACh ) 的 response.ResultsNon 侵略的 iontophoretic 管理，一个已知的内皮细胞层依赖者扩张器，在本地流动得到了增加。氮的氧化物 synthase 禁止者， l-N-Arginine- 甲基酉旨(L 名字) ，堵住了 BNP 反应(在控制) 。有趣地，对在 CHF 病人的 BNP 的回答被归结为在健康控制看见的大约三分之一那些(的增加流动：251% 在 CHF 对 908% 在控制；P &#x0003c；0.001 ) 。相反，对 ACh 并且到本地加热的血管扩张药回答仅仅有点在 CHF 病人被稀释。因此，发信号的扩张器能力和氮的氧化物没被影响到象调停 BNP 的膨胀的一样的程度，第一次显示后者 response.ConclusionsThe 调查结果表演的特定的 downregulation 对 BNP 的 microvascular 回答显著地在 CHF 病人被减少。这与 BNP 受体功能的假设一致是在 CHF 的 downregulated。

Protective Effect of Sodium Tanshinone ⅡA Sulfonate on Injury of Small Intestine in Rats with Sepsis and Its Mechanism

Objective:To explore the protective effect of sodium tanshinoneⅡA sulfonate(STS) on small intestine injury in rats with sepsis and its possible mechanism.Methods:According to a random number table, 24 Tats were randomly divided into 3 groups:sham operation group(sham group),sepsis model group(model group) and STS treatment group(STS group),with 8 Tats in each group.A rat model of sepsis was induced by cecal ligation and puncture(CLP) for 5 h.STS(1 mg/kg) was slowly injected through the right external jugular vein after CLP.The histopathologic changes in the intestine tissue were observed under a light microscope,and the intestinal epithelial cell apoptosis was evaluated by terminal deoxynucleoddyl transferase(TdT)-mediated dUTP nick-end labeling(TUNEL) method.The expressions of Bcl-2,Bax and nuclear factorκB(NF-κB) p65 in the intestinal tissue was determined by Western blot.The levels of tumor necrosis factorα(TNF-α) and interleukin 6(IL-6) in the intestinal tissue were determined using enzyme-linked immuno-sorbent assay(ELISA). Results:Obvious injuries were observed in the intestinal tissue in the CLP group compared with the sham group. The expression of NF-κB p65 and the levels of TNF-αand IL-6 were up-regulated after CLP,the apoptosis of intestinal epithelial cells was increased after CLP,and the ratio of Bcl-2 to Bax was decreased.STS posttreatment could attenuate the injury on the intestinal tissue induced by CLP,decrease the apoptosis of intestinal epithelial cells and the levels of NF-κB p65,TNF-αand IL-6,and increase the ratio of Bcl-2 to Bax.Conclusion: STS can protect the small intestine in rats with sepsis,and the mechanism may be associated with the inhibition of intestinal epithelial apoptosis and the reduction of activation of inflammatory cytokines.

Effect of Sodium Tanshinone ⅡA Sulfonate on Cardiac Myocyte Hypertrophy and Its Underlying Mechanism

<正>Objective:To investigate the effects of sodium tanshinoneⅡA sulfonate(STS)on the hypertrophy induced by angiotensinⅡ(AngⅡ)in primary cultured neonatal rat cardiac myocytes. Methods:The effect of STS on cytotoxicity was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-3,5- phenytetrazoliumromide(MTT)assay.As indexes for cardiocyte hypertrophy,cell size was determined by phase contrast microscopy and protein synthesis rate was measured by ~3H-leucine incorporation. The proto-oncogene c-fos mRNA expression of cardiocytes was assessed using reverse transcription polymerase chain reaction(RT-PCR).Results:STS could inhibit cardiocyte hypertrophy,increase the protein synthesis rate,and enhance proto-oncogene c-fos mRNA expression in cardiocytes induced by AngⅡ(P<0.01),with an effect similar to that of Valsartan,the AngⅡreceptor antagonist.Conclusion:STS can prevent the hypertrophy of cardiac myocytes induced by AngⅡ,which may be related to its inhibition of the expression of proto-oncogene c-fos mRNA.

Effect of Sodium Tanshinone ⅡA Sulfonate on Phosphorylation of Extracellular Signal-regulated Kinasel/2 in Angiotensin Ⅱ-induced Hypertrophy of Myocardial Cells

Objective:To observe the effects of sodium tanshinoneⅡA sulfonate(STS) on angiotensinⅡ(AngⅡ)-induced hypertrophy of myocardial cells through the expression of phosphorylated extracellular signal-regulated kinase(p-ERK1/2).Methods:In the primary culture of neonatal rat myocardial cells,the total protein content in myocardial cells was determined by coomassie brilliant blue and the protein synthesis rate was measured by[3H]-Leucine incorporation as indexes for hypertrophy of myocardial cells.The expression of p-ERK1/2 was determined using Western blot and immunofluorescence labeling.Results:(1)The total protein and protein synthesis rate increased significantly in contrast to the control group after the myocardial cells were stimulated by AngⅡ(1μmol/L)for 24 h;STS markedly inhibited the increment of the total protein level induced by AngⅡand the syntheses of protein.(2)After pretreatment of myocardial cells with AngⅡ(1μmol/L)for 5 min,the p-ERK1/2 protein expression was increased,with the most obvious effect shown at about 10 min;pretreatment of myocardial cells with STS at different doses(2,10, 50μmol/L)for 30 min resulted in obvious inhibition of the expression of p-ERK1/2 stimulated by AngⅡin a dose-dependent manner.(3)After the myocardial cells were stimulated by AngⅡ(1μmol/L), the immunofluorescence of ERK1/2 rapidly appeared in the nucleus.The activation and translocation process of ERK1/2 induced by AngⅡwas blocked distinctly by STS.Conclusion:STS inhibited the myocardial cell hypertrophy induced by AngⅡ,and the mechanism may be associated with the inhibition of p-ERK1/2 expression.

Characteristics of convicted male-on-female rapists in the South of Sweden between 2013 and 2018:a pilot study

The objective of this study was to evaluate the main characteristics of adult male offenders convicted of rape or aggravated rape against adult females.We reviewed all convictions(n=21)based on court documents from the District Court,the Court of Appeal and information from the Swedish Tax Agency in Malmo,Sweden,between 2013 and 2018.The findings indicated that the most common offender characteristics were a single status,mean age of 33 years and foreign background.The rapes primarily occurred within a private setting while the victims(who were often younger and knew the offender)were unconscious.Although assumptions based on these results should be made with caution,our findings provide a clear image of the typical circumstances under which these rapes occurred.This study should be viewed as a first attempt to create a database of characteristics of convicted rapists.As more data are added,more sophisticated analyses can be performed and stronger generalizations may be made.Information of this kind may also be important for further research,classification of rapists in offender profiling,and case linking.

Investigating the impact of air pollution on AMI and COPD hospital admissions in the coastal city of Qingdao,China

Air pollution has been widely associated with adverse effects on the respiratory and cardiovascular systems.We investigated the relationship between acute myocardial infarction(AMI),chronic obstructive pulmonary disease(COPD)and air pollution exposure in the coastal city of Qingdao,China.Air pollution in this region is characterized by inland and oceanic transportation sources in addition to local emission.We examined the influence of PM_(2.5),PM_(10),NO_(2),SO_(2),CO and O_(3) concentrations on hospital admissions for AMI and COPD from October 1,2014,to September 30,2018,in Qingdao using a Poisson generalized additive model(GAM).We found that PM_(2.5),PM_(10),NO_(2),SO_(2) and CO exhibited a significant short-term(lag 1 day)association with AMI in the singlepollutant model among older adults(>65 years old)and females,especially during the cold season(October to March).In contrast,only NO2 and SO2 had clear cumulative lag associations with COPD admission for females and those over 65 years old at lag 01 and lag 03,respectively.In the twopollutant model,the exposure-response relationship fitted by the two-pollutant model did not change significantly.Our findings indicated that there is an inflection point between the concentration of certain air pollutants and the hospital admissions of AMI and COPD even under the linear assumption,indicative of the benefits of reducing air pollution vary with pollution levels.This study has important implications for the development of policy for air pollution control in Qingdao and the public health benefits of reducing air pollution levels.

Echinacoside Protects Against MPP+-Induced Neuronal Apoptosis via ROS/ATF3/CHOP Pathway Regulation

Echinacoside(ECH) is protective in a mouse model of Parkinson's disease(PD) induced by 1-methyl-4-phenylpyridinium ion(MPP^+). To investigate the mechanisms involved, SH-SY5Y neuroblastoma cells were treated with MPP^+or a combination of MPP^+and ECH,and the expression of ATF3(activating transcription factor3), CHOP(C/EBP-homologous protein), SCNA(synuclein alpha), and GDNF(glial cell line-derived neurotrophic factor) was assessed. The results showed that ECH significantly improved cell survival by inhibiting the generation of MPP^+-induced reactive oxygen species(ROS). In addition, ECH suppressed the ROS and MPP^+-induced expression of apoptotic genes(ATF3, CHOP, and SCNA). ECH markedly decreased the MPP^+-induced caspase-3 activity in a dose-dependent manner. ATF3-knockdown also decreased the CHOP and cleaved caspase-3 levels and inhibited the apoptosis induced by MPP^+.Interestingly, ECH partially restored the GDNF expression that was down-regulated by MPP^+. ECH also improved dopaminergic neuron survival during MPP^+treatment and protected these neurons against the apoptosis induced by MPTP. Taken together, these data suggest that the ROS/ATF3/CHOP pathway plays a critical role in mechanisms by which ECH protects against MPP^+-induced apoptosis in PD.

非编码RNA的选择性作用：编码与非编码特性研究进展（英文）

非编码RNA在细胞生物学功能中发挥着重要作用。近年来,研究人员在生物发育和多种疾病中发现了一些由非编码RNA(ncRNA)编码产生的多肽或蛋白质。在本文中,我们简要总结了几种由ncRNA翻译的微肽分子及其功能。此外,我们还总结了调控ncRNA的可能机制,并且提出了一个生物“开关”,即细胞在一定的刺激或应激状态下,能够触发ncRNA分子由非编码状态到编码状态的转换。ncRNA的潜在编码特性及其微肽产物为蛋白质组学研究提供了一个新的视角,有希望为多种疾病提供新的治疗靶点。

Holding Sweden hostage:firearm-related violence

Swedish as well as foreign publications have reported a sharp increase in firearm-related violence in Sweden. None of these publications, however, combined official statistics from the Swedish police, the National Council for Crime Prevention (NCCP), and the National Board of Health and Welfare (NBHW), to study firearm-related violence in the last 2 years:2016–2017. The results of this study show that firearm-related violence in Sweden has greatly increased compared to other Scandinavian countries, especially in recent years. This is probably the reason for the increase in the rate of deadly violence. Further, the increasing number of gangs and criminal networks, as well as the high inflow of illegal firearms to Sweden, is believed to have contributed to the disturbing increase of firearm-related vio-lence in the country. Although Sweden is one of the most democratic and freest countries in the world, and has some of the world's strictest gun laws, the country still faces signifi-cant firearm-related violence. This study not only reveals the increasing rate of firearm-related violence in Sweden, but also shows that Sweden is in dire need of additional policies to combat the illegal flow of firearms and to curb gang criminality.