The development of the neurocritical care specialty in China based on the analysis of neurocritical care unit volume and quality.

PURPOSE: Through three neurocritical care unit (NCCU) surveys in China, we tried to understand the development status of neurocritical care and clarify its future development. METHODS: Using a cross-sectional survey method and self-report questionnaires, the number and quality of NCCUs were investigated through three steps: administering the questionnaire, sorting the survey data, and analyzing the survey data. RESULTS: At the second and third surveys, the number of NCCUs (76/112/206) increased by 47% and 84%, respectively. The NCCUs were located in tertiary grade A hospitals or teaching hospitals (65/100/181) in most provinces (24/28/29). The numbers of full-time doctors (359/668/1337) and full-time nurses (904/1623/207) in the NCCUs increased, but the doctor-bed ratio and nurse-bed ratio were still insufficient (0.4:1 and 1.3:1). CONCLUSION: In the past 20 years, the growth rate of NCCUs in China has accelerated, while the allocation of medical staff has been insufficient. Although most NCCU hospital bed facilities and instruments and equipment tend to be adequate, there are obvious defects in some aspects of NCCUs.

The initial treatment in convulsive status epilepticus in China: A multi-center observational study.

OBJECTIVE: To investigate the initial treatment of patients with convulsive status epilepticus (CSE) in a resource-limited region of China, and to discuss the difference of in-hospital outcomes and economic costs between those with guideline-recommended initial treatment and those without. METHODS: In this retrospective study, we screened adult patients discharged with the diagnosis of CSE in four centers in west China. Individuals with different exposure to the initial drug were divided into benzodiazepine (BDZ) and non-BDZ group for outcome comparison. The primary outcomes were seizure control, and the ratio of patients who developed refractory SE. The secondary outcomes included in-hospital mortality, the modified Rankin Scale (mRS) score at discharge, in-hospital respiratory support rate, length, and cost of the stay. RESULTS: Three-hundred and thirteen patients (127, 40.6% were women) with CSE were included. The median age was 43 (range 16-92). There were 152 (48.6%) patients initially treated with BDZ. Among the 36 who received midazolam as initial treatment, twenty-six received an insufficient dose. The other 116 (76.3%) patients in the BDZ group chose diazepam as initial treatment. Fifteen of them (12.9%) were treated underdose. In the non-BDZ group (161, 51.4%), antiseizure medications (ASMs) and/or coma-induced drugs were used as initial treatment. Among those initially administrated ASMs, intramuscular phenobarbital (38,37.6%) and valproate (46, 52.3%) were most frequently seen. There was a significant difference in the time latency to initial treatment and etiology between BDZ and non-BDZ group. The non-BDZ group reported a higher cessation rate after initial treatment compared to the BDZ group (P = 0.012). No significant difference in other primary and secondary outcomes. SIGNIFICANCE: Non-adherence and underdosing of the initial treatment of SE were common in China. However, the non-BDZ group showed a better seizure control rate. The effect came from early aggressive medication, that is, the combination of ASMs and anesthesia. Non-BDZ group was not inferior to BDZs in terms of seizure control, the occurrence of in-hospital death, and poor outcome at discharge. More robust evidence is needed in developing settings when choosing the initial treatment.

The development of neurocritical care in China from the perspective of evaluation and treatment of critical neurological diseases.

Objective: To understand the varieties, evaluation, treatment, and prognosis of severe neurological diseases using the third NCU survey in China. Design: A cross-sectional questionnaire study. The study was completed in three main steps: filling in the questionnaire, sorting out the survey data, and analyzing the survey data. Results: Of 206 NCUs, 165 (80%) provided relatively complete information. It was estimated that 96,201 patients with severe neurological diseases were diagnosed and treated throughout the year, with an average fatality rate of 4.1%. The most prevalent severe neurological disease was cerebrovascular disease (55.2%). The most prevalent comorbidity was hypertension (56.7%). The most prevalent complication was hypoproteinemia (24.2%). The most common nosocomial infection was hospital-acquired pneumonia (10.6%). The GCS, APACHE II, EEG, and TCD were the most commonly used (62.4-95.2%). The implementation rate of the five nursing evaluation techniques reached 55.8-90.9%. Routinely raising the head of the bed by 30°, endotracheal intubation and central venous catheterization were the mostprevalent treatment strategies (97.6, 94.5, and 90.3%, respectively). Traditional tracheotomy, invasive mechanical ventilation and nasogastric tube feeding (75.8, 95.8, and 95.8%, respectively) were more common than percutaneous tracheotomy, non-invasive mechanical ventilation and nasogastric tube insertion (57.6, 57.6, and 66.7%, respectively). Body surface hypothermia brain protection technology was more commonly used than intravascular hypothermia technology (67.3 > 6.1%). The rates of minimally invasive hematoma removal and ventricular puncture were only 40.0 and 45.5%, respectively. Conclusion: In addition to traditional recognized basic life assessment and support technology, it is necessary to the use of promote specialized technology for neurological diseases, according to the characteristics of critical neurological diseases.

Complete genome analysis of PaGz-1 and PaZq-1, two novel phages belonging to the genus Pakpunavirus.

Pseudomonas phages PaGz-1 and PaZq-1, two new phages infecting Pseudomonas aeruginosa, were isolated from fresh water in Guangdong province, China. The genomes of these two phages consist of 93,975 bp and 94,315 bp and contain 175 and 172 open reading frames (ORFs), respectively. The genome sequences of PaGz-1 and PaZq-1 share 95.8% identity with a query coverage of 94%, suggesting that these two phages belong to two different species. Based on results of nucleotide sequence alignment, gene annotation, and phylogenetic analysis, we propose PaGz-1 and PaZq-1 as representative isolates of two species in the genus Pakpunavirus within the family Myoviridae.

Electrokinetic remediation of uranium(VI)-contaminated red soil using composite electrolyte of citric acid and ferric chloride.

In the process of electrokinetic (EK) remediation of uranium-contaminated soil, the existence form of uranium in soil pore fluid will affect on its migration behavior. In this paper, a novel type of electrolyte (citric acid + ferric chloride, CA+ FeCl3) has been investigated for the EK remediation of uranium-contaminated red soil. The effects of different electrolyte and the concentrations of FeCl3 on migration behavior of U(VI) and environmental risks were investigated after EK remediation. The result showed that the optimum concentration was 0.1 mol/L CA mixed with 0.03 mol/L FeCl3 in this study. At this time, the removal efficiency of uranium was about 61.55 ± 0.41%, and the cumulative energy consumption was 0.2559 kWh. Compared with deionized water and single CA, combined CA with FeCl3 has the advantages of high removal efficiency, low leaching toxicity, and less damage to the soil after the electrokinetic remediation treatment.

A Task Scheduling Algorithm for Phased-Array Radar Based on Dynamic Three-Way Decision.

The time resource management of phased-array radars is the key to fulfilling their performance, such as how phased-array radar can efficiently and reasonably schedule tasks under limited resources. Therefore, this paper proposes a task scheduling algorithm for phased-array radar based on dynamic three-way decision. The algorithm introduces three-way decision into the scheduling algorithm and divides the target into three threat areas according to the threat degree (i.e., threat area, nonthreat area, and potential threat area). Different threat domains are assigned different weights and combine the working mode and the task deadline to carry out comprehensive priority planning, so that the radar can reasonably allocate time according to the difference of the target threat level and the threat area in the tracking stage. In addition, an improved adaptive threshold algorithm is proposed to obtain a dynamic three-way decision to achieve the adaptation of the algorithm. A set of performance indicators have been defined to evaluate the algorithm. The relevant experiments have demonstrated that the proposed algorithm can effectively improve the processing capability of phased-array radars when dealing with high-threat targets.

Mastoiditis caused by intracranial venous sinus stenting in an idiopathic intracranial hypertension patient.

The exact mechanism of idiopathic intracranial hypertension (IIH) is unknown. It needs to be treated because of severe headache and impaired vision. For medically refractory patients, cerebrospinal fluid diversion, optic nerve sheath fenestration and dural venous sinus stenting is applied to relieve the symptoms. As a new therapy, the complication of dural venous stenting was a focus for operators. Here, a woman is reported with IIH who suffered from mastoiditis after stenting in the sigmoid sinus for the first time. The special local anatomy of the sigmoid sinus adjacent to the inner structure made it a noteworthy complication.

Characterization and complete genomic analysis of two Salmonella phages, SenALZ1 and SenASZ3, new members of the genus Cba120virus.

Salmonella phages SenALZ1 and SenASZ3, two novel phages infecting Salmonella enterica, were isolated and analyzed. The genomes of these two phages consist of 154,811 and 157,630 base pairs (bp), with G+C contents of 44.56% and 44.74%, respectively. Fifty-nine of 199 open reading frames (ORFs) in the SenALZ1 genome, and 60 of the 204 in the SenASZ3 genome show similarity to reference sequences in the NCBI nr database that encode putative phage proteins with predicted functions. Based on the results of transmission electron microscopy (TEM) examination, complete genome sequence alignment, phylogenetic analysis, and gene annotation, we propose that these two phages are representative isolates of two new species of the genus Cba120virus, subfamily Cvivirinae, family Ackermannviridae.

Activation of the Akt/mTOR signaling pathway: A potential response to long-term neuronal loss in the hippocampus after sepsis.

Survivors of sepsis may suffer chronic cognitive impairment as a long-term sequela. However, the precise mechanisms of cognitive dysfunction after sepsis are not well understood. We employed the cecal ligation-and-puncture-induced septic mouse model. We observed elevated phosphorylation of Akt, mammalian target of rapamycin (mTOR) and p70S6K on days 14 and 60, progressive neuronal loss in the cornu ammonis 1 region, and abnormal neuronal morphology in the hippocampus in the sepsis mouse model. These findings indicate that changes in neuronal morphology and number in the hippocampus after sepsis were associated with strong activation of the Akt/mTOR signaling pathway, and may reflect a "self-rescuing" feedback response to neuronal loss after sepsis.

Rapamycin Protects Sepsis-Induced Cognitive Impairment in Mouse Hippocampus by Enhancing Autophagy.

The purpose of this study is to test the hypothesis that the mammalian target of rapamycin (mTOR) signaling pathway might mediate neuroprotection in a mouse model of septic encephalopathy and also to identify the role of autophagy. Mice were subjected to cecal ligation and puncture (CLP) or a sham operation, and all 50 mice were randomly assigned to five groups: sham, CLP+ saline, CLP+ rapamycin (1, 5, 10 mg/kg) groups. Two weeks after the operation, Morris water maze was conducted for behavioral test; Nissl staining was used for observing glia infiltration; immunohistochemical staining and biochemical measures in hippocampi were performed to detect mTOR targets and autophagy indicators. Immunochemistry revealed significant loss of neurons and increased glia infiltration in hippocampus after CLP operation. Inhibition of mTOR by rapamycin rescued cognitive deficits caused by sepsis (p < 0.05). Rapamycin did not affect total mTOR targets, while phosphorylated mTOR targets (p-mTOR-Ser2448, p-p70S6k-Thr389, p-AKT-S473) decreased (p < 0.05) and autophagy indicators (LC3-II, Atg5, Atg7) were increased, and P62 was decreased in rapamycin-treated CLP mice compared with the untreated (p < 0.05) in hippocampus. Rapamycin improves learning after sepsis through enhancing autophagy and may be a potentially effective therapeutic agent for the treatment of sepsis-induced cognitive impairment.

Update on causes of premature death in people with convulsive epilepsy in rural West China.

This longitudinal prospective study updated a previous report on premature mortality and focused on the risk factors among patients with convulsive epilepsy in resource-poor settings. The present cohort size (7,231) and follow-up (mean 33.4 months) were expanded. The basic epidemiologic aspects of this cohort were similar to the original report (case fatality: 3.26% vs. 2.97%, respectively; injury contributed more than half of the deaths). Cox regression analysis suggested that male patients, late ages of onset (>45 years old), short duration of epilepsy (<10 years), and high convulsive seizure frequency (>2 per month) were independent risk factors for overall premature death. Male patients with late ages of onset and high seizure frequency had a higher risk of injury-specific death. This study emphasizes the preventable nature of injuries that are leading putative causes of death among people with convulsive epilepsy in rural West China. Education on specific populations and efficient seizure control are of paramount importance in reducing the risk of premature mortality.

A preliminary observation of the adverse effects of phenobarbital among patients with convulsive epilepsy in rural West China.

BACKGROUND: This study explored the adverse effect (AE) profile of phenobarbital (PB) among patients with active convulsive epilepsy (ACE) from resource-poor areas. METHODS: Patients with ACE were enrolled into an epilepsy management project in rural West China. Information was obtained from monthly follow-up questionnaires. The demographic and clinical features of the patients with AE were firstly described. After that, the occurrence rate was estimated for each subtype of AE at three different severity levels (mild, moderate, and serious). Survival analysis was used to determine the potential risk factors of AEs. RESULTS: A total of 7231 patients (3780 men) were included in the present cohort. During the follow-up time period (average 33.4months), the most common AEs were drowsiness (moderate: 4.4%, serious: 0.68%), dizziness (moderate: 3.7%, serious: 0.5%), and headache (moderate: 2.9%, serious: 0.41%). In the confirmed AE groups (moderate and serious severity levels), the symptoms tended to be transient, with durations of less than 3months. Polytherapy was an independent risk factor for AEs and had an increasing risk when the severity of the AE increased (Hazard Ratio 1.12, 1.55, and 2.52 for mild AE, moderate AE, and serious AE, respectively). Receiving a high dosage of PB (>180mg/day) indicated a slightly elevated risk (Hazard Ratio 1.22 and 1.27 for mild AE and moderate AE, respectively). CONCLUSION: Phenobarbital demonstrates overall tolerability, and serious AEs were not common. Patients receiving a high dose of PB or polytherapy are at increased risk of developing AEs.

Clinical features and outcome of super-refractory status epilepticus: a retrospective analysis in West China.

PURPOSE: Data about super-refractory status epilepticus (SRSE) are scarce. This study aimed to assess the clinical features and outcome of patients with SRSE. METHOD: Clinical features of all SRSE patients admitted to the Neurologic Intensive Care Unit (NICU)/Neurology Department of West China Hospital, Sichuan University, between January 2010 and August 2013, were retrospectively analyzed. Outcome at discharge, at the three-month and long-term follow-ups were evaluated using the Glasgow Outcome Scale (GOS). Possible predictors of mortality and outcome were also evaluated. RESULTS: Thirteen patients with SRSE were included. Young patients with encephalitis accounted for the majority of the series (61.5%). In-hospital mortality was 15.4% (2/13), and the three-month mortality was 36.4% (4/11; two patients ceasing therapy were excluded). At the long-term follow-up, 18.2% of patients improved and 45.5% of patients recovered. Patients of older age and those with multiple complications had higher mortality compared with those of younger age and those with fewer complications. For survivors, functional outcome had significantly improved at three-month follow-up (GOS score=4.1 ± 1.2) compared to that at discharge (GOS score=3.1 ± 1.2, P<0.05). Long duration of anesthesia, etiology of encephalitis and positive neuroimaging findings tended to be associated with poor functional outcome. CONCLUSION: We conclude that the typical patient susceptible to development of SRSE in West China is a young patient with encephalitis. Older age and multiple complications increase the risk of death. Most patients can survive with aggressive therapy, and their functional outcome improves over time.

Etiologic features of newly diagnosed epilepsy: hospital-based study of 892 consecutive patients in West China.

PURPOSE: We evaluated data from a large cohort of newly diagnosed epilepsy patients from the biggest epilepsy center in West China. The aim was to determine the most prevalent etiologic factors in this region. METHODS: From May 2008 to May 2010, the clinical data of patients with newly diagnosed epilepsy were consecutively, systematically and prospectively recorded in a database. The data were analyzed according to sex, age, seizure type, etiology, and other factors. RESULTS: The present study examined 892 patients with newly diagnosed epilepsy. Among these patients, 346 (38.8%) were confirmed as symptomatic, with the largest constituent ratio among the elderly (63.2%). In this symptomatic group, central nervous system (CNS) infections and traumatic brain injuries (TBI) were the two most common etiologies. When analyzed according to age bracket, cortical dysplasia, mesial temporal sclerosis, and CNS infection were the most frequent causes among young patients (<18 years). On the other hand, CNS infection and TBI were the two most common causes in patients between 18 and 60 years. Stroke was the most common cause of newly diagnosed symptomatic epilepsy in the elderly (>60 years). CONCLUSIONS: More than 30% of newly diagnosed epilepsy cases were shown to be symptomatic by medical history as well as careful clinical and laboratory examination. Detailed epilepsy assessments are essential to formulate a therapeutic plan and to improve prognosis. The etiology spectrum found in this large cohort forms a comparative baseline for future studies.

Evaluation of the efficiency of inpatient 24-hour VEEG combined with MRI in consecutive patients with newly diagnosed epilepsies.

A total of 128 patients were recruited into this study to evaluate the cost efficiency of 24-hour video electroencephalography (VEEG) combined with magnetic resonance imaging (MRI) in people with newly diagnosed epilepsies. The rate of neuroimaging abnormalities detected was 14.8% higher with MRI than with computed tomography (CT), whereas 25.7% more EEG abnormalities were detected with inpatient 24-hour VEEG than with outpatient EEG. In the partial seizure (PS) group, MRI combined with 24-hour VEEG revealed that 20 of 73 (27.4%) patients had local epileptogenic lesions, whereas CT with outpatient EEG revealed a rate of 10 in 73 (13.7%). With respect to the economic impact, 27.3% of the patients spent more than 17.8% of their annual household income for 24-hour VEEG and MRI. However, 82.7% of the patients spent less than that, and among these patients, only 16.4% spent less than 5.9% of their annual household income. Hence, we conclude that the combination of MRI and 24-hour VEEG as a compulsory tool should be popularized in less developed countries.

Features of the K-complex waves in refractory nocturnal frontal lobe epilepsy.

PURPOSE: To investigate the features of the K-complex (Kc) in refractory nocturnal frontal lobe epilepsy (NFLE) and its relationship with spike discharges (Sds) and clinical seizures. METHODS: Long-term video-electroencephalographic (VEEG) monitoring was used to collect Kc data from NFLE patients and age- and sex-matched controls. We compared the morphological and frequency changes in Kcs between the intractable NFLE group and the control group. Also, the morphological changes in Kcs with Sds and seizures were compared with the other Kcs in NFLE patients. RESULTS: In the NFLE group, frequency, amplitude, and rising slope (except duration) were higher than in the control group. Out of the 30 seizures recorded, nine (30%) commenced after a Kc. These Kcs had higher amplitudes than the other Kcs in the NFLE group; there was no difference in duration or rising slope. Additionally, 28 (13.86%) of 202 Kcs of the NFLE group occurred in conjunction with Sds; there were no obvious morphological differences compared with other Kcs. CONCLUSION: Kc activity increases in NFLE, especially prior to a clinical seizure. This reflects an unstable sleep condition, which suggests a correlation between Kc and epileptic activities including seizures and Sds.

[Separation, culture and purification of rat brain microendothelial cell].

OBJECTIVE: To develop a separation method for brain microendothelial cells with the comparison of other ones. METHODS: Twice enzymatic digestion and twice gradient centrifugation were applied to separate rat brain microendothelial cells. Then, immunomagnetic beads and Thy1.1 antibody were used respectively to purify the cultured cells. RESULTS: Twice enzymatic digestion and twice gradient centrifugation could separate the cell successfully. High purification but low cell yield was obtained with immunomagnetic beads. The cells handled with Thy1.1 antibody had both higher purify coefficient and higher yield. CONCLUSION: The developed method could separate the brain microendothelial cells successfully.

Suppression of the multidrug transporter P-glycoprotein using RNA interference in cultured rat astrocytes induced by coriaria lactone.

The overexpression of the multidrug resistance gene (MDR-1) and its translational product p-glycoprotein (P-gp) may play an important role in pharmacoresistant epilepsy. We established the rat astrocyte model overexpressing P-gp induced by coriaria lactone and successfully nucleofected it with the siRNA-hairpin expression vector pSIREN-shuttle designed to target MDR-1B mRNA. The mRNA expression of MDR-1B gene was mostly knock down by 67.70% (p<0.01). The expression of P-gp in experimental group was significantly lower than that in negative control (p<0.05), and the rhodamine efflux ratio of experimental group (23.08%) was remarkably lower than that of negative control (78.35%, p<0.01). We first employed RNA interfering to the drug resistance reversal of refractory epilepsy and this may provide a new way for refractory epilepsy remedy.

RNAi inhibits Coriaria lactone-induced MDR1b overexpression in rat brain microvascular endothelial cells.

P-glyprotein (multidrug resistance gene 1, MDR1) was the first isolated and most extensively investigated refractory epilepsy-related drug-resistant protein. Coriaria lactone (CL) can induce P-glyprotein expression of brain capillary and astrocytes in vivo. We established the primary rat brain microvascular endothelial cell (BMECs) models overexpressing P-glycoprotein induced by CL successfully and infected them with adenovirus vector, which carry small interfering RNA (siRNA) designed to target MDR1b. MDR1b mRNA levels and P-glyprotein expression in experimental group decreased significantly 72 h after infection, and the fluorescence intensity of rhodamine within the cells of experimental group increased significantly. So, CL can induce P-glyprotein overexpression in BMECs in vitro, and siRNA can effectively inhibit expression of P-glyprotein and decrease its "pumping out" function. This may offer a new method and rationale for studying the mechanism of refractory epilepsy and relevant gene therapy.

Inhibition of P-glycoprotein over-expression by shRNA-mdr1b in rat astrocytes.

The development of multiple drug resistance (MDR) is a significant problem in epilepsy therapy. The primary factor responsible for antiepileptic drug (AEDs) resistance is the over-expression of the MDR gene product, P-glycoprotein (Pgp). To model a therapeutic approach for decreasing drug resistance in patients with intractable epilepsy, we established a model of coriaria lactone (CL) induced Pgp overexpression in rat astrocytes and administered a recombinant adenovirus Ad5-EGFP-shRNA1-U6 to deliver an anti-mdr1b short hairpin RNA (shRNA) for 5 days. We then investigated the gene-silencing effects of shRNA by quantitative real-time RT-PCR, Western-blot, and Rho123 accumulation assay. The results showed that over-expression of mdr1b and Pgp was successfully suppressed, the ability of intracellular Rho123 retention was increased, and drug efflux was decreased in the adenovirus treated astrocytes. In conclusion, MDR was reversed in rat astrocyte model. These findings may be favorable for developing new therapeutic strategies for treating intractable epilepsy.