胸部创伤合并心功能和心肌细胞损害的早期监测与临床观察

目的:探讨血清N末端B型钠尿肽原(NT-proBNP)和心脏型脂肪酸结合蛋白(h-FABP)在胸部创伤所致心肌挫伤的早期监测价值,并观察重组人生长激素(rhGH)的治疗效果。方法:选择82例胸部创伤合并心肌挫伤患者(挫伤组)和50例健康人(对照组)为研究对象,挫伤组采用rhGH治疗。血清NT-proBNP检测采用电化学发光免疫分析(ECLIA)法,血清h-FABP检测采用双抗体夹心酶联免疫(ELISA)一步法。结果:治疗前血清h-FABP阳性率(41.4%)显著高于NT-proBNP(29.8%)及心电图(ECG)(17.7%)(P<0.01)。治疗前,胸部创伤合并心肌挫伤患者血清NT-proBNP和h-FABP水平分别与对照组比较差异有统计学意义(P<0.01);治疗后,两者水平均显著低于治疗前(P<0.01),与对照组比较,差异无统计学意义(P>0.05)。胸部创伤合并心肌挫伤患者血清NT-proBNP与h-FABP呈显著正相关(r=0.719,P<0.01),相关性良好。胸部创伤合并心肌挫伤的82例患者经rhGH治疗后,血清NT-proBNP和h-FABP水平达正常,ECG也无异常表现,无一例死亡病例。结论:rhGH对胸部创伤合并心肌挫伤具有临床治疗作用,血清NT-proBNP和h-FABP的联合检测可早期诊断胸部创伤合并心功能及心肌细胞损害,也可观察临床疗效。     

N末端B型脑钠肽前体在不典型心力衰竭诊断中的应用价值

目的 探讨N末端B型脑钠肽前体（NT-proBNP）对不典型心力衰竭的诊断价值.方法 选择深圳市人民医院2010年5月至2012年5月病房住院患者疑诊为临床症状不典型心力衰竭264例,检测血清NT-proBNP水平,同时完善胸部X线片、超声心动图等心功能不全相关辅助检查,比较NT-proBNP界值法、超声心动图参数法及实用内科学标准法对心力衰竭的阳性检出率.结果 NT-proBNP界值法、超声心动图参数法及实用内科学标准法评判,检出阳性率分别为93.9％（248/264）、70.1％（185/264）、58.3％（154/264）.阳性率采用非参数独立样本秩和检验比较,各组之间差异有统计学意义（Z=90.488,P=0.000）;3种评判方法两两比较,采用矫正检验水准α=0.017,NT-proBNP界值法与超声心动图参数法及实用内科学标准法评判阳性率比较,差异均有统计学意义（Z =50.849,P=0.000;Z =91.933,P=0.000）;超声心动图参数法及实用内科学标准法评判阳性率比较,差异有统计学意义（Z =7.904,P=0.005）.结论 NT-proBNP界值法在不典型心力衰竭中的诊断价值优于超声心动图参数法及实用内科学标准法评判法.     

Withdrawal of Neurohumoral Blockade After Cardiac Resynchronization Therapy

BackgroundThe necessity of neurohumoral blockers in patients with heart failure who demonstrate normalized ejection fractions after cardiac resynchronization therapy remains unclear.ObjectiveSThe aim of this study was to investigate the feasibility and safety of neurohumoral blocker withdrawal in patients with normalized ejection fractions after cardiac resynchronization therapy.MethodsIn this prospective, open-label, randomized controlled pilot trial with a 2 × 2 factorial design, subjects were randomized to withdrawal of renin-angiotensin-aldosterone system inhibitors and/or beta-blockers versus continuation of treatment. The primary endpoint was a recurrence of negative remodeling, defined as an increase in left ventricular end-systolic volume index of >15% at 24 months. The secondary endpoint was a composite safety endpoint of all-cause mortality, heart failure–related hospitalizations, and incidence of sustained ventricular arrhythmias at 24 months.ResultsEighty subjects were consecutively enrolled and randomized among 4 groups (continuation of neurohumoral blocker therapy, n = 20; withdrawal of renin-angiotensin-aldosterone system inhibitors, n = 20; withdrawal of beta-blockers, n = 20; and withdrawal of renin-angiotensin-aldosterone system inhibitors and beta-blockers, n = 20). Of the 80 subjects, 6 (7.5%) met the primary and 4 (5%) the secondary endpoint. However, re-initiation of neurohumoral blockers occurred in 17 subjects because of hypertension or supraventricular arrhythmias.ConclusionsThe incidence of the primary and secondary endpoints over a follow-up period of 2 years was low in both the control group and in the groups in which neurohumoral blockers were discontinued. However, neurohumoral blocker withdrawal was hampered by cardiac comorbidities. (Systematic Withdrawal of Neurohumoral Blocker Therapy in Optimally Responding CRT Patients [STOP-CRT]; NCT02200822)     

Reproductive actions of prolactin mediated through short and long receptor isoforms

Prolactin (PRL) is a polypeptide hormone with a wide range of physiological functions, and is critical for female reproduction. PRL exerts its action by binding to membrane bound receptor isoforms broadly classified as the long form and the short form receptors. Both receptor isoforms are highly expressed in the ovary as well as in the uterus. Although signaling through the long form is believed to be more predominant, it remains unclear whether activation of this isoform alone is sufficient to support reproductive functions or whether both types of receptor are required. The generation of transgenic mice selectively expressing either the short or the long form of PRL receptor has provided insight into the differential signaling mechanisms and physiological functions of these receptors. This review describes the essential finding that both long and short receptor isoforms are crucial for ovarian functions and female fertility, and highlights novel mechanisms of action for these receptors.     

Increased soluble (pro)renin receptor protein by autophagy inhibition in cultured cancer cells

(Pro)renin receptor ((P)RR) regulates the renin–angiotensin system and functions as an essential accessory subunit of vacuolar H⁺‐ATPase. There is accumulating evidence that shows close relationship between (P)RR and autophagy. Soluble (P)RR consisting of the extracellular domain of (P)RR is generated from (P)RR by proteolytic enzymes. The aim of the present study was to clarify the influence of autophagy inhibition on soluble (P)RR expression in cancer cells. Autophagy was inhibited by treatment of bafilomycin A1 or chloroquine in MCF‐7 and A549 cells for 72 hr. Western blot analysis showed that protein levels of soluble (P)RR were markedly elevated by autophagy inhibition, whereas no noticeable increases were observed in full‐length (P)RR. Secretion of soluble (P)RR into the medium was increased dose‐dependently by bafilomycin A1 or chloroquine. Autophagy inhibition was confirmed by enhanced accumulation of autophagy‐related proteins, LC3, p62 and LAMP1 in intracellular vesicles. Increased amount of soluble (P)RR by autophagy inhibition was decreased by site‐1 protease inhibitor, whereas no noticeable increase in site‐1 protease immunoreactivity was observed in cells with autophagy inhibition by immunocytochemistry. These findings suggest that soluble (P)RR protein accumulates by autophagy inhibition, possibly because of the reduced degradation of soluble (P)RR in the intracellular vesicles during autophagy inhibition.     

Leptin induces secretion of pro‐inflammatory cytokines by human keratinocytes in vitro – a possible reason for increased severity of psoriasis in patients with a high body mass index

Investigations about prevalence of obesity in psoriasis patients are increased nowadays. Higher serum levels of leptin in patients with psoriasis who are overweight or obese suggest that leptin may serve as a molecular link between psoriasis and metabolic comorbidities. However, the pathological functions of leptin in psoriasis are not clearly understood. We investigated the influence of being overweight or obese on the risk of psoriasis, and the relationship between serum leptin levels and the severity of psoriasis in Chinese Han patients. We also investigated biological effects of leptin on the proliferation and secretion of pro‐inflammatory cytokines by human keratinocytes in vitro. Obesity was a significant risk factor for psoriasis in the Chinese Han population; however, we did not observe a significant correlation between Psoriasis Area and Severity Index (PASI) and body mass index (BMI). We observed a positive correlation between the serum leptin level and PASI in overweight and obese male patients with psoriasis. Strong leptin immunoreactivity was detected in the epidermis of psoriatic lesions, particularly in keratinocytes. Leptin significantly increased the proliferation and secretion of pro‐inflammatory cytokines by keratinocytes in vitro. In conclusion, this study suggests leptin as a novel molecular link between psoriasis and obesity, which may help to explain the more server conditions of psoriasis in patients with obesity.