Long-term outcomes and independent predictors of mortality in patients presenting to emergency departments with acute heart failure in Beijing: a multicenter cohort study with a 5-year follow-up.

BACKGROUND: Acute heart failure (AHF) is the most common disease in emergency departments (EDs). However, clinical data exploring the outcomes of patients presenting AHF in EDs are limited, especially the long-term outcomes. The purposes of this study were to describe the long-term outcomes of patients with AHF in the EDs and further analyze their prognostic factors. METHODS: This prospective, multicenter, cohort study consecutively enrolled 3335 patients with AHF who were admitted to EDs of 14 hospitals from Beijing between January 1, 2011 and September 23, 2012. Kaplan-Meier and Cox regression analysis were adopted to evaluate 5-year outcomes and associated predictors. RESULTS: The 5-year mortality and cardiovascular death rates were 55.4% and 49.6%, respectively. The median overall survival was 34 months. Independent predictors of 5-year mortality were patient age (hazard ratio [HR]: 1.027, 95 confidence interval [CI]: 1.023-1.030), body mass index (BMI) (HR: 0.971, 95% CI: 0.958-0.983), fatigue (HR: 1.127, 95% CI: 1.009-1.258), ascites (HR: 1.190, 95% CI: 1.057-1.340), hepatic jugular reflux (HR: 1.339, 95% CI: 1.140-1.572), New York Heart Association (NYHA) class III to IV (HR: 1.511, 95% CI: 1.291-1.769), heart rate (HR: 1.003, 95% CI: 1.001-1.005), diastolic blood pressure (DBP) (HR: 0.996, 95% CI: 0.993-0.999), blood urea nitrogen (BUN) (HR: 1.014, 95% CI: 1.008-1.020), B-type natriuretic peptide (BNP)/N-terminal pro-B-type natriuretic peptide (NT-proBNP) level in the third (HR: 1.426, 95% CI: 1.220-1.668) or fourth quartile (HR: 1.437, 95% CI: 1.223-1.690), serum sodium (HR: 0.980, 95% CI: 0.972-0.988), serum albumin (HR: 0.981, 95% CI: 0.971-0.992), ischemic heart diseases (HR: 1.195, 95% CI: 1.073-1.331), primary cardiomyopathy (HR: 1.382, 95% CI: 1.183-1.614), diabetes (HR: 1.118, 95% CI: 1.010-1.237), stroke (HR: 1.252, 95% CI: 1.121-1.397), and the use of diuretics (HR: 0.714, 95% CI: 0.626-0.814), ß-blockers (HR: 0.673, 95% CI: 0.588-0.769), angiotensin-converting enzyme inhibitors (ACEIs) (HR: 0.714, 95% CI: 0.604-0.845), angiotensin-II receptor blockers (ARBs) (HR: 0.790, 95% CI: 0.646-0.965), spironolactone (HR: 0.814, 95% CI: 0.663-0.999), calcium antagonists (HR: 0.624, 95% CI: 0.531-0.733), nitrates (HR: 0.715, 95% CI: 0.631-0.811), and digoxin (HR: 0.579, 95% CI: 0.465-0.721). CONCLUSIONS: The results of our study demonstrate poor 5-year outcomes of patients presenting to EDs with AHF. Age, BMI, fatigue, ascites, hepatic jugular reflux, NYHA class III to IV, heart rate, DBP, BUN, BNP/NT-proBNP level in the third or fourth quartile, serum sodium, serum albumin, ischemic heart diseases, primary cardiomyopathy, diabetes, stroke, and the use of diuretics, ß-blockers, ACEIs, ARBs, spironolactone, calcium antagonists, nitrates, and digoxin were independently associated with 5-year all-cause mortality.

Incidence and outcome of adult in-hospital cardiac arrest in Beijing, China.

OBJECTIVE: To assess the incidence and outcome of in-hospital cardiac arrests (IHCAs) in Beijing, China. METHODS: The incidence and outcome of IHCAs over a 12-month period were evaluated in this prospective study. Between January 1 and December 31, 2014, 12 Beijing hospitals prospectively participated in this study for calculation of the incidence of IHCA. Data were collected according to the Utstein style for all cases of attempted resuscitation for IHCA that occurred in the participating hospitals. Surviving patients were followed for 1 month. RESULTS: The total number of admissions across the 12 hospitals during this 1-year period was 582,242; the IHCA incidence was 17.5 per 1000 admissions. Of the 10,198 IHCAs recorded, cardiopulmonary resuscitation (CPR) was initiated in 26.6%. Among CPR recipients, 1292 (47.6%) had a presumed cardiac aetiology and 1255 occurred in the Emergency Department. With regards to initial rhythm, 1340 had asystole and 423 had shockable rhythms. Of those receiving CPR, 1451 (53.5%) patients received it in less than 1min. Restoration of spontaneous circulation was achieved in 962 (35.5%) patients; 247 (9.1%) patients were discharged alive and 174 (6.4%) patients had good neurological outcomes. At 1 month after discharge, 236 patients remained alive. On multivariate regression analysis, factors associated with survival included female sex, age <60 years, and ventricular fibrillation/ventricular tachycardia as the initial rhythm. CONCLUSION: The incidence of IHCA in Beijing hospitals is high and the survival is poor compared to other industrialized countries.

[Progress in the effects of injury and regeneration of gustatory nerves on the taste functions in animals].

The sensor of the taste is the taste bud. The signals originated from the taste buds are transmitted to the central nervous system through the gustatory taste nerves. The chorda tympani nerve (innervating the taste buds of the anterior tongue) and glossopharyngeal nerve (innervating the taste buds of the posterior tongue) are the two primary gustatory nerves. The injuries of gustatory nerves cause their innervating taste buds atrophy, degenerate and disappear. The related taste function is also impaired. The impaired taste function can be restored after the gustatory nerves regeneration. The rat model of cross-regeneration of gustatory nerves is an important platform for research in the plasticity of the central nervous system. The animal behavioral responses and the electrophysiological properties of the gustatory nerves have changed a lot after the cross-regeneration of the gustatory nerves. The effects of the injury, regeneration and cross-regeneration of the gustatory nerves on the taste function in the animals will be discussed in this review. The prospective studies on the animal model of cross-regeneration of gustatory nerves are also discussed in this review. The study on the injury, regeneration and cross-regeneration of the gustatory nerves not only benefits the understanding of mechanism for neural plasticity in gustatory nervous system, but also will provide theoretical basis and new ideas for seeking methods and techniques to cure dysgeusia.

Effect of siRNA­induced inhibition of IL­6 expression in rat cerebral gliocytes on cerebral edema following traumatic brain injury.

The present study aimed to investigate the effect of RNA interference (RNAi) on the inhibition of interleukin (IL)­6 expression in rat cerebral gliocytes in vitro and rat cerebral traumatic tissues in vivo, as well as the effect of RNAi on cerebral edema. pSUPER vectors containing IL­6 small hairpin RNA (pSUPER­IL­6 1­5) were designed, constructed and transfected into C6 rat glioma cells using cationic liposomes. ELISA was used to select the plasmid with the strongest interference effect. A freefall method was used to generate a rat brain injury model and rats were randomly divided into treatment, empty plasmid and control groups (n=14/group). IL­6 levels, water content and sodium content were determined in the brain tissues at 24 and 72 h post­injury. pSUPER­IL­6 was effectively transfected into C6 cells and was found to inhibit the expression of IL­6 rather than IL­8. The pSUPER­IL­6 1 vector was most effective in inducing RNAi. In vivo, IL­6 levels were observed to be lowest in the interference group and there were statistically significant differences in water and sodium content among the experimental groups (P<0.05). RNAi was found to inhibit IL­6 expression in vivo and in vitro in rat cerebral gliocytes, and the reduction of the IL­6 levels was found to reduce post­traumatic cerebral edema.

Effects of chronic cold exposure on murine central nervous system.

Recently, cold-adaptation medicine has gotten more and more attention because of its specific significance to health care, military activities, sports performance, and so on. Although numerous studies have focused on respiratory, immune, and circulatory systems as well as skin damage upon cold exposure, the impacts on central nervous system are not well understood. This study explores the effects of chronic cold exposure on the murine central nervous system. To establish a chronic cold-exposure animal model, adult male mice from postnatal days 40-50 (P40-50) were housed at 0-4°C for 20 days. During the study period, estrogen receptors were labeled via immunohistochemistry, the dendritic spines of visual cortical pyramidal cells were labeled with DiI diolistic assay, and synaptic ultrastructure was observed by transmission electron microscopy. The results showed that cold exposure could inhibit neural proliferation significantly, with an increase of G-protein-coupled receptor 30 (GPR30) expression. Chronic cold exposure could also induce a decrease in the dendritic spines of pyramidal cells in visual cortex, along with a decrease in the number of synaptic formations. The ultrastructure of synapses after cold exposure was observed. It was found that pre- and postsynaptic membranes were fused, with a vague synaptic cleft. Furthermore, neuronal cytoplasmic and organelle swellings were also observed, along with microtubule disintegration. In conclusion, chronic cold exposure can cause structural and functional changes in the mouse central nervous system, possibly by direct participation of estrogen and its receptor, GPR30, in response to chronic cold exposure.

Gastrointestinal bleeding after intracerebral hemorrhage: a retrospective review of 808 cases.

BACKGROUND: This study examined the incidence and risk factors for gastrointestinal (GI) bleeding after spontaneous intracerebral hemorrhage (ICH). METHODS: The available medical records of patients with ICH admitted from June 2008 to December 2009 for any episode of GI bleeding, possible precipitating factors and administration of ulcer prophylaxis were reviewed. RESULTS: The prevalence of GI bleeding was 26.7%, including 3 cases of severe GI bleeding (0.35%). Patients with GI bleeding had significantly longer hospital stay and higher in-hospital mortality compared with patients without GI bleeding. Multivariate logistic regression analyses showed that age, Glasgow Coma Scale scores, sepsis and ICH volume were independent predictors of GI bleeding. About 63.4% of patients with ICH received stress ulcer prophylaxis. CONCLUSIONS: GI bleeding occurred frequently after ICH, but severe events were rare. Age, Glasgow Coma Scale score, sepsis and ICH volume were independent predictors of GI bleeding occurring after ICH.

[Sodium nitrite induces PC12 cell differentiation].

To investigate the potential ability of the nitrite to induce neuronal differentiation of PC12 cells, cultured PC12 cells planted on matrigel in the presence or absence of sodium nitrite were employed as model, nerve growth factor (NGF) served as a positive control. After 48 h, sodium nitrite enhanced cell viability and vascular endothelial growth factor (VEGF) secretion. Same as the effect of NGF, sodium nitrite (1.4 mmol x L(-1)) treated cultures contained a greater proportion of cells bearing neurites and neurites were much longer than those found in negative control cultures (P < 0.05). Compared with the negative control, sodium nitrite (1.4 mmol x L(-1)) also upregulated the expression of VEGF mRNA (P < 0.05) and hypoxia inducible factor 1 alpha (HIF-1 alpha) or VEGF protein expression (P < 0.05) in cultures of PC12 cells. On the other hand, these effects of the sodium nitrite were likely mediated by HIF-1alpha, since their effects were antagonized by addition of HIF-1alpha inhibitor YC-1. Taken together, these results suggest that low doses of sodium nitrite could induce neurite outgrowth in PC12 cells by activating the HIF-1alpha-VEGF pathway.

The effects of prenatal alcohol exposure on the developmental retina of mice.

AIMS: Our aim is to investigate the effects of prenatal alcohol exposure (PAE) on the development of retinal bipolar and horizontal cells. METHODS: The alterations of the retinal bipolar and horizontal cells in P7, P14 and P30 mice were observed after PAE, with immunofluorescent labeling and DiI diolistic assay. RESULTS: The retinal development of filial pups was affected by PAE in a dose-dependent and long-term manner. The number of bipolar cells of alcohol groups was significantly lower than that of the control, and the dendritic receptive field of horizontal cells was also significantly smaller than those of the control groups (P < 0.01). CONCLUSION: PAE was able to cause retarded development of pup retinal neural cells.

Lower variability of tacrolimus trough concentration after conversion from prograf to advagraf in stable kidney transplant recipients.

BACKGROUNDS: Variability of blood trough concentration (C0) in immunosuppressant leads to rejection and graft loss after kidney transplantation. METHODS: The aim of this study is to prospectively investigate the change of within-patient variability among stable kidney transplant recipients with conversion from twice-daily Prograf to the same milligram-for-milligram daily dose of once-daily Advagraf. RESULTS: The mean age of 129 patients was 51.3±12.1 years. The conversion to Advagraf was administrated at 6.3±4.8 years after transplantation. The daily dose was changed from 4.7±2.0 mg to 4.9±2.1 mg after conversion. Only six patients increased daily dose by 16.7% to 25% to maintain target levels. The whole blood C0 of tacrolimus before conversion was 5.9±1.7 ng/mL. The mean C0 was significantly reduced after conversion to Advagraf; it was 4.9±1.5 ng/mL on the seventh day (P<0.001) and 5.4 to 5.5 ng/mL at 1 to 6 months (P<0.05). Forty-one (31.8%) patients have reduced C0 of more than 25% on the seventh day. The percent coefficient of variation of tacrolimus C0 more than 22.5% before conversion is associated with higher risk of reduced C0 after conversion (P<0.05). Compared with before conversion, less kidney transplant recipients have percent coefficient of variation more than 22.5% after conversion (3.1% vs. 17.4% with P<0.01). CONCLUSIONS: The results support that conversion from Prograf to Advagraf among kidney transplant recipient leads to a significantly lower C0 and within-patient variability of tacrolimus C0. The within-patient variability of C0 before conversion influences C0 on the sevent day after conversion to Advagraf.

High risk of renal failure in stage 3B chronic kidney disease is under-recognized in standard medical screening.

BACKGROUND: The objective of this study was to determine the risk of renal failure in patients with under-recognized chronic kidney disease (CKD) in the self-pay standard medical screening program of health management centers. METHODS: The abbreviated Modification of Diet in Renal Disease equation was used to calculate the estimated glomerular filtration rate (eGFR) of study subjects. Study subjects with eGFR less than 60 mL/min/1.73m(2) but with normal results of routine assessment, including serum creatinine, blood urea nitrogen, urinalysis and kidney ultrasound, were defined as having under-recognized CKD. Episodes of renal failure requiring dialysis within 2 years in subjects with stage 3 to stage 5 CKD were evaluated. RESULTS: A total of 15,817 subjects were recruited and 28.4% of subjects were identified by routine assessments as having a kidney problem. The prevalences of CKD 3A, 3B, 4 and 5 were 8.3%, 1.9%, 0.3% and 0.2%, respectively. All subjects with stages 4 and 5 CKD had abnormal serum creatinine levels, but 48.7% of 1,507 subjects with stage 3 CKD (stage 3A, n = 713; stage 3B, n = 21) had normal routine assessments. Subjects with under-recognized stage 3B CKD had the highest risk (20%) of developing renal failure compared to subjects with stages 3-5 CKD and abnormal results of routine assessments. CONCLUSION: Identifying subjects with CKD stage 3 by the eGFR equation, especially in stage 3B, is advantageous in detecting the risk of renal failure over the routine clinical assessment that is currently carried out by health management institutions in Taiwan.

[Effects of alcohol exposure during pregnancy on dendritic spine and synapse of visual cortex in filial mice].

The prenatal ethanol exposure induced the alterations of dendritic spine and synapse in visual cortex and their long-term effect would be investigated in mice from P0 to P30. Pregnant mice were intubated ethanol daily from E5 through the pup's birth to establish mode of prenatal alcohol abuse. The dendritic spines of pyramidal cells in visual cortex of pups were labeled with DiI diolistic assay, and the synaptic ultrastructure was observed under transmission electron microscope. Prenatal alcohol exposure was associated with a significant decrease in the number of dendritic spines of pyramidal neurons in the visual cortex and an increase in their mean length; ultrastructural changes were also observed, with decreased numbers of synaptic vesicles, narrowing of the synaptic cleft and thickening of the postsynaptic density compared to controls. Prenatal alcohol exposure is associated with long-term changes in dendritic spines and synaptic ultrastructure. The changes were dose-dependent with long term effect even at postnatal 30.

Prenatal alcohol exposure induces long-term changes in dendritic spines and synapses in the mouse visual cortex.

AIMS: To study the long-term changes of dendritic spine and synapse taking place in a mouse model of fetal alcohol spectrum disorders (FASDs). METHODS: Pregnant mice were intubated daily with ethanol (EtOH) from E5 to parturition. A DiI diolistic method was used to label dendritic spines of pyramidal cells in the visual cortex of EtOH-exposed and control pups over the period from postnatal (P) day P0 to P30; synaptic ultrastructure was also analyzed using transmission electron microscopy. RESULTS: Prenatal alcohol exposure was associated with a significant decrease in the number of dendritic spines of pyramidal neurons in the visual cortex and an increase in their mean length. The changes were dose dependent and persisted to P30. Ultrastructural changes were also observed, with decreased numbers of synaptic vesicles, narrowing of the synaptic cleft and thickening of the postsynaptic density compared to controls; ultrastructural changes also persisted to P30. CONCLUSIONS: Prenatal alcohol exposure is associated with long-term changes in dendritic spines and synaptic ultrastructure; these alterations probably reflect the developmental retardation of dendritic spines and synapses in visual cortex. These long-term changes are likely to contribute to lifelong mental retardation associated with childhood FASDs.

Expression of the apoptosis-related proteins caspase-3 and NF-kappaB in the hippocampus of Tg2576 mice.

OBJECTIVE: To investigate the relations between neuroapoptosis and the onset and development of Alzheimer's disease (AD), especially the role of NF-kappaB in the regulation of neuroapoptosis. METHODS: Caspase-3 and NF-kappaB (p50) expressions in the CA3 region of the hippocampus in APPswe Tg2576 transgenic mice were studied from postnatal day 0-180, using Nissl staining, immunohistochemistry and RT-PCR methods. RESULTS: Both neuronal apoptosis and NF-kappaB activity decreased gradually with the increase of age in wild type and Tg2576 mice. However, the number of caspase-3-positive or NF-kappaB-positive pyramidal cells in Tg2576 mice was greater than that in age-matched wild type mice, with significant differences after postnatal day 14 (P < 0.01 or P < 0.05). Linear regression analyses of caspase-3 and NF-kappaB expression demonstrated a correlation between neuroapoptosis and activity of NF-kappaB. CONCLUSION: The process of neuroapoptosis is consistent with the onset and development of AD. Furthermore, the observed correlation between neuroapoptosis and NF-kappaB activity suggests a role of NF-kappaB in hippocampal neuroapoptosis.

The synaptic remodeling between regenerated perforant pathway and granule cells in slice culture.

In order to understand the synaptic remodeling in the course of axonal regeneration, the synaptic remodeling of the perforant path in hippocampus was investigated in the present study with entorhino-hippocampal coculture, DiI DiOlistic assay and transmission electron microscopy. The results showed that the regeneration of the perforant pathway occurred in entorhino-hippocampal slice coculture, and putative synaptic contacts formed between the regenerated fibers and dendritic spines of granule cells. Ultrastructural analysis confirmed the formation of new synaptic contacts. In conclusion, the synaptic formation implicated in the neuroregeneration could integrate into the network in CNS.

Reelin, a guidance signal for the regeneration of the entorhino-hippocampal path.

The importance of reelin for cortical lamination in the developing CNS is well established, but its role in nerve fiber growth is not well understood. In this study, hippocampal slices were co-cultured with entorhinal slices of GFP mice, in order to compare the growth of the entorhino-hippocampal path in wild type and reeler mice. On day 6, regenerated fibers were seen to navigate from the entorhinal cortex into the hippocampus. The results showed that in wild type mice, regenerated fibers grew along the molecular layer of the dentate gyrus, and only a few fibers were found to penetrate through the granular layer into the hilus. This specific orientation was similar to the perforant path in vivo. Compared with perforant path regeneration in wild type mice, reeler mice seemed to have lost their specific orientation and proper termination in the hippocampus. Without the guidance signal from reelin, the regenerated fibers left the molecular layers and continued to grow aberrantly, i.e., in the granular layer, hilus, pyramidal layer and even stratum oriens. Particularly in the dentate gyrus, the fibers meandered around the cells in the hilus and resembled a network. The study concludes that reelin also serves as an important guidance signal for neuroregeneration of the perforant path.

The tracing study of developing entorhino-hippocampal pathway.

The entorhino-hippocampal pathway is the major excitatory input from neurons of the entorhinal cortex on both ipsilateral and contralateral hippocampus/dentate gyrus. This fiber tract consists of the alvear path, the perforant path and a crossed commissural projection. In this study, the histogenesis and development of the various subsets of the entorhino-hippocampal projection have been investigated. DiI, DiO, Fast Blue tracing and calretinin immunocytochemistry as well as were carried out with pre and postnatal rats at different developmental stages. The alvear path and the commissural pathway start to develop as early as embryonic day E16, while the first perforant afferents reach the stratum lacunosum-moleculare of the hippocampus at E17 and at outer molecular layer of the denate gyrus at postnatal day 2. Retrograde tracing with DiI identifies entorhinal neurons in layer II-IV as the developmental origin of the entorhino-hippocampal pathway. Furthermore, calretinin immunocytochemistry revealed transitory Cajal-Retzius cells in the stratum lacunosum-moleculare of the hippocampus from E16. DiI labeling of entorhinal cortex fibers and combined calretinin-immunocytochemistry reveal a close relationship between Cajal-Retzius cells and entorhinal afferents. This temporal and spatial relationship suggests that Cajal-Retzius cell serves as a guiding cue for entorhinal afferents at early cortical development.

Formation of the entorhino-hippocampal pathway: a tracing study in vitro and in vivo.

Objective The entorhino-hippocampal pathway is the major excitatory input from neurons of the entorhinal cortex on both ipsilateral and contralateral hippocampus/dentate gyrus. This fiber tract consists of the alvear path, the perforant path and a crossed commissural projection. In this study, the histogenesis and development of the various subsets of the entorhino-hippocampal projection have been investigated. Methods DiI, DiO and fast blue tracing as well as anti-calretinin immunocytochemistry were carried out with prenatal and postnatal rats at different ages. Results The alvear path and the commissural pathway started to develop as early as embryonic day (E) 16, while the first perforant afferents reached the stratum lacunosum-moleculare of the hippocampus at E17 and the outer molecular layer of dentate gyrus at postnatal day (P) 2, respectively. Retrograde tracing with DiI identified entorhinal neurons in layer II to IV as the origin of entorhino-hippocampal pathway. Furthermore, anti-calretinin immunocytochemistry revealed transitory Cajal-Retzius (CR) cells in the stratum lacunosum-moleculare of the hippocampus from as early as E16. DiI labeling of entorhinal cortex fibers and combined calretinin-immunocytochemistry showed a close association between CR cells and entorhinal afferents. Conclusion The subsets of entorhino-hippocampal pathway appear in the developmental hippocampus during E16-P2. The temporal and spatial relationship between CR cell and perforant afferent suggests the role of this cell type as a guiding cue for entorhinal afferents at early cortical development.