Single-dose methamphetamine administration impairs ORM retrieval in mice via excessive DA-mediated inhibition of PrLGlu activity.

Methamphetamine (METH), an abused psychostimulant, impairs cognition through prolonged or even single-dose exposure, but animal experiments have shown contradictory effects on memory deficits. In this study we investigated the effects and underlying mechanisms of single-dose METH administration on the retrieval of object recognition memory (ORM) in mice. We showed that single-dose METH administration (2 mg/kg, i.p.) significantly impaired ORM retrieval in mice. Fiber photometry recording in METH-treated mice revealed that the activity of prelimbic cortex glutamatergic neurons (PrLGlu) was significantly reduced during ORM retrieval. Chemogenetic activation of PrLGlu or glutamatergic projections from ventral CA1 to PrL (vCA1Glu-PrL) rescued ORM retrieval impairment. Fiber photometry recording revealed that dopamine (DA) levels in PrL of METH-treated mice were significantly increased, and micro-infusion of the D2 receptor (D2R) antagonist sulpiride (0.25 µg/side) into PrL rescued ORM retrieval impairment. Whole-cell recordings in brain slices containing the PrL revealed that PrLGlu intrinsic excitability and basal glutamatergic synaptic transmission were significantly reduced in METH-treated mice, and the decrease in intrinsic excitability was reversed by micro-infusion of Sulpiride into PrL in METH-treated mice. Thus, the impaired ORM retrieval caused by single-dose METH administration may be attributed to reduced PrLGlu activity, possibly due to excessive DA activity on D2R. Selective activation of PrLGlu or vCA1Glu-PrL may serve as a potential therapeutic strategy for METH-induced cognitive dysfunction.

Preoperative prediction of the lymphovascular tumor thrombus of colorectal cancer with the iodine concentrations from dual-energy spectral CT.

BACKGROUND: The aim of this study was to explore application value of iodine concentration from dual-energy spectral computed tomography (DESCT) in preoperative prediction of lymphovascular tumor thrombus in patients with colorectal cancer (CRC). METHODS: We finally retrospectively analyzed 50 patients with CRC who underwent abdominal DESCT before receiving any preoperative treatment and underwent surgery to obtain pathological specimens which were stained with hematoxylin-eosin (HE) staining. According to the presence of cancer cell nests in blood vessels and lymphatic vessels, the subjects were divided into the positive group and negative group of lymphovascular tumor thrombus. Two radiologists independently measured the normalized iodine concentration (NIC) values, effective atomic number (Zeff) and CT values of virtual monochromatic images (VMIs) at 40-90 keV of the primary tumors in the arterial phase (AP) and venous phase (VP). Used SPSS 17.0 to calculate the receiver operating characteristic (ROC) curve to evaluate diagnostic value. RESULTS: The patients were divided into lymphovascular tumor thrombus positive group(n = 16) and negative group(n = 34). The values of NIC-AP and NIC-VP in the positive group were 0.17 ± 0.09, 0.51 ± 0.13, respectively. And those in the negative group were 0.15 ± 0.06, 0.43 ± 0.12, respectively. There was significant difference in NIC-VP value between the two groups (p = 0.039), but there was no significant difference in NIC-AP value (p = 0.423). The optimal threshold value of NIC-VP value for diagnosis of lymphovascular tumor thrombus was 0.364. The sensitivity was 68.8% and the specificity was 67.6%. CONCLUSIONS: The NIC-VP value of DESCT can be used to predict the presence or absence of the lymphovascular tumor thrombus in CRC patients before operation, which is helpful to select the best treatment scheme and evaluate its prognosis.

Surgical outcomes of basilar invagination type B without atlantoaxial dislocation through simple posterior fossa decompression: a retrospective study of 18 cases.

BACKGROUND: Basilar invagination (BI) is a common disease in the craniocervical junction (CVJ) area. Posterior fossa decompression with/without fixation is a controversial surgical strategy for BI type B. This study aimed to evaluate the efficacy of simple posterior fossa decompression in treating BI type B. METHODS: This study retrospectively enrolled BI type B patients who underwent simple posterior fossa decompression at Huashan Hospital, Fudan University between 2014.12 and 2021.12. Patient data and images were recorded pre- and postoperatively (at the last follow-up) to evaluate the surgical outcomes and craniocervical stability. RESULTS: A total of 18 BI type B patients (13 females), with a mean age of 44.2±7.9 years (range 37-62 years), were enrolled. The mean follow-up period was 47.7±20.6 months (range 10-81 months). All patients received simple posterior fossa decompression without any fixation. At the last follow-up, compared with preoperation, the JOA scores were significantly higher (14.2±1.5 vs. 9.9±2.0, p = 0.001); the CCA was improved (128.7±9.6° vs. 121.5±8.1° p = 0.001), and the DOCL was reduced (7.9±1.5 mm vs. 9.9±2.5 mm, p = 0.001). However, the follow-up and preoperative ADI, BAI, PR, and D/L ratio were similar. No patients had an unstable condition between the C1-2 facet joints that was observed in the follow-up CT and dynamic X-ray. CONCLUSIONS: In BI type B patients, simple posterior fossa decompression could improve neurological function and will not induce CVJ instability in BI type B patients. Simple posterior fossa decompression could be a satisfactory surgical strategy for BI type B patients, but preoperative CVJ stability assessment is crucial.

Pseudoginsenoside-F11 attenuates cognitive dysfunction and tau phosphorylation in sporadic Alzheimer's disease rat model.

We previously reported that pseudoginsenoside-F11 (PF11), an ocotillol-type saponin, significantly ameliorated Alzheimer's disease (AD)-associated cognitive defects in APP/PS1 and SAMP8 mice by inhibiting Aß aggregation and tau hyperphosphorylation, suggesting a potential therapeutic effect of PF11 in the treatment of AD. In the present study we further evaluated the therapeutic effects of PF11 on relieving cognitive impairment in a rat model of sporadic AD (SAD). SAD was induced in rats by bilateral icv infusion of streptozotocin (STZ, 3 mg/kg). The rats were treated with PF11 (2, 4, 8 mg·kg-1·d-1, ig) or a positive control drug donepezil (5 mg·kg-1·d-1, ig) for 4 weeks. Their cognitive function was assessed in the nest building, Y-maze, and Morris water maze tests. We showed that STZ icv infusion significantly affected the cognitive function, tau phosphorylation, and insulin signaling pathway in the hippocampus. Furthermore, STZ icv infusion resulted in significant upregulation of the calpain I/cyclin-dependent protein kinase 5 (CDK5) signaling pathway in the hippocampus. Oral administration of PF11 dose-dependently ameliorated STZ-induced learning and memory defects. In addition, PF11 treatment markedly reduced the neuronal loss, protected the synapse structure, and modulated STZ-induced expression of tau phosphorylation by regulating the insulin signaling pathway and calpain I/CDK5 signaling pathway in the hippocampus. Donepezil treatment exerted similar beneficial effects in STZ-infused rats as the high dose of PF11 did. This study highlights the excellent therapeutic potential of PF11 in managing AD.

Berberine improves intralipid-induced insulin resistance in murine.

Insulin resistance (IR) is a major metabolic risk factor even before the onset of hyperglycemia. Recently, berberine (BBR) is found to improve hyperglycemia and IR. In this study, we investigated whether BBR could improve IR independent of hyperglycemia. Acute insulin-resistant state was induced in rats by systemic infusion of intralipid (6.6%). BBR was administered via different delivery routes before or after the beginning of a 2-h euglycemic-hyperinsulinemic clamp. At the end of experiment, rats were sacrificed, gastrocnemius muscle was collected for detecting mitochondrial swelling, phosphorylation of Akt and AMPK, as well as the mitochondrial permeability regulator cyclophilin D (CypD) protein expression. We showed that BBR administration markedly ameliorated intralipid-induced IR without affecting blood glucose, which was accompanied by alleviated mitochondrial swelling in skeletal muscle. We used human skeletal muscle cells (HSMCs), AML12 hepatocytes, human umbilical vein endothelial cells, and CypD knockout mice to investigate metabolic and molecular alternations. In either HSMCs or AML12 hepatocytes, BBR (5 µM) abolished palmitate acid (PA)-induced increase of CypD protein levels. In CypD-deficient mice, intralipid-induced IR was greatly attenuated and the beneficial effect of BBR was diminished. Furthermore, we demonstrated that the inhibitory effect of BBR on intralipid-induced IR was mainly mediated by skeletal muscle, but not by intestine, liver, or microvasculature; BBR administration suppressed intralipid-induced upregulation of CypD expression in skeletal muscle. These results suggest that BBR alleviates intralipid-induced IR, which is related to the inhibition of CypD protein expression in skeletal muscle.

Bufalin induces protective autophagy by Cbl-b regulating mTOR and ERK signaling pathways in gastric cancer cells.

Bufalin, a natural small-molecule compound derived from the traditional Chinese medicine Chan su, has shown promising anti-cancer effects against a broad variety of cancer cells through different mechanisms. It has been reported to induce autophagy in gastric cancer cells. However, the molecular mechanism involved is not fully elucidated. In the present study, we aimed to investigate the molecular mechanism by which bufalin induce autophagy in human gastric cancer cells. We found that bufalin induced apoptosis and autophagy in gastric cancer cells, and autophagy prevented human gastric cancer cells from undergoing apoptosis. Bufalin treatment changed the expression of autophagy-related proteins. Moreover, phosphorylated Akt, mTOR, and p70S6K were all significantly decreased, while phosphorylated ERK1/2 was increased by bufalin. Pretreatment of MGC803 cells with the ERK1/2-specific inhibitor PD98059 led to the down-regulation of LC3 II. Further study showed that Cbl-b positively regulated autophagy by suppressing mTOR and enhancing ERK1/2 activation. Therefore, our data provide evidence that bufalin induces autophagy in MGC803 cells via both Akt/mTOR/p70S6K and ERK signaling pathways, and Cbl-b-mediated suppression of mTOR and activation of ERK1/2 might play an important role.

[Personality and psychological characteristics of premature ejaculation patients].

OBJECTIVE: To investigate the personality and psychological characteristics of premature ejaculation (PE) patients and the correlation between them two. METHODS: Using Eysenck Personality Questionnaire (EPQ) and Symptom Checklist 90 (SCL-90), we conducted an investigation among 94 PE patients seeking medical advice in Drum Tower Hospital from October 2018 to February 2019. RESULTS: The neuroticism score of the PE patients on EPQ was significantly higher than the national norm of adult males (t = 12.010, P < 0.01), and so was their introversion-extroversion score (t = 2.557, P < 0.05), while their concealment score was markedly lower (t = －8.736, P < 0.01). The coercion score of the patients on SCL-90 was remarkably higher than the national norm of adult males (t = 2.787, P < 0.01), and so were their psychosis score (t = 3.944, P < 0.01) and anxiety score (t = 2.512, P < 0.05). There was a significant correlation between the EPQ and SCL-90 scores of the patients. Psychoticism was found highly positively correlated with terror (r = 0.455, P < 0.01), interpersonal relationship (r = 0.295, P < 0.01), hostility (r = 0.375, P < 0.01), psychosis (r = 0.363, P < 0.01), compulsion (r = 0.284, P < 0.01), depression (r = 0.294, P < 0.01), paranoia (r = 0.336, P < 0.01), somatization (r = 0.400, P < 0.01) and anxiety (r = 0.358, P < 0.01), and so was neuroticism with terror (r = 0.466, P < 0.01), interpersonal relationship (r = 0.611, P < 0.01), hostility (r = 0.509, P < 0.01), psychosis (r = 0.593, P < 0.01), compulsion (r = 0.573, P < 0.01), depression (r = 0.560, P < 0.01), paranoia (r = 0.550, P < 0.01), somatization (r = 0.465, P < 0.01) and anxiety (r = 0.572, P < 0.01). Introversion-extroversion, however, was highly negatively correlated with interpersonal relationship (r = －0.226, P < 0.05) and depression (r = －0.228, P < 0.05), and so was concealment with terror (r= － 0.351, P < 0.01), interpersonal relationship (r = －0.433, P < 0.01), hostility (r = －0.347, P < 0.01), psychosis (r = －0.427, P < 0.01), compulsion (r = －0.345, P < 0.01), depression (r = －0.379, P < 0.01) , paranoia (r = －0.393, P < 0.01), somatization (r = －0.204, P < 0.05) and anxiety (r =－0.237, P < 0.05). CONCLUSIONS: The personality and psychological status of PE patients are different from those of normal males, and some personality characteristics of the patients are correlated with their psychological status, especially with high neuroticism.

Interpreting the Chinese version of quality of life questionnaire for functional digestive disorders.

BACKGROUND AND AIM: The Chinese version quality of life questionnaire for functional digestive disorders (Chin-FDDQL) is a useful health assessment instrument for functional dyspepsia. This study aims to identify its score interpretation for clinical practice. METHODS: Data of Chin-FDDQL from the functional dyspepsia patients (≥ 18 years) between November 2009 and April 2013 were enrolled in the 1st and 14th day. After baseline and responsiveness analysis, the single score interpretation and percentile ranks were established. The statistically reliable change was defined with effect size, standardized response mean, minimal detectable change, and others. Then the receiver operating characteristic curve analysis for health improvement was performed to define the clinically important change. RESULTS: Two hundred two functional dyspepsia patients, 150 healthy participants, and 25 missing data were enrolled for analysis. Compared with the intake patients, the discharged and healthy persons have significant better health status in all domains (P < 0.001, expect discomfort in discharged people, P = 0.142), totally contrast to missing data. The reliability for single total intake and discharge were both ± 1. Based on score distribution, the 25th, 50th, and 75th percentile ranks were 49, 58, and 66 for intake scores and 59, 65, and 72 for discharge scores, respectively. The minimal detectable change and Reliable Change Index were 6 and 11 for total score. Receiver operating characteristic analyses supported that total score changes 4 or more represented minimal clinically important improvement. CONCLUSIONS: The score interpretation system of the Chin-FDDQL could assist clinician's decision making during the therapy practice.

The Influence of Cellulosic Polymer's Variables on Dissolution/Solubility of Amorphous Felodipine and Crystallization Inhibition from a Supersaturated State.

The collective impact of cellulosic polymers on the dissolution, solubility, and crystallization inhibition of amorphous active pharmaceutical ingredients (APIs) is still far from being adequately understood. The goal of this research was to explore the influence of cellulosic polymers and incubation conditions on enhancement of solubility and dissolution of amorphous felodipine, while inhibiting crystallization of the drug from a supersaturated state. Variables, including cellulosic polymer type, amount, ionic strength, and viscosity, were evaluated for effects on API dissolution/solubility and crystallization processes. Water-soluble cellulosic polymers, including HPMC E15, HPMC E5, HPMC K100-LV, L-HPC, and MC, were studied. All cellulosic polymers could extend API dissolution and solubility to various extents by delaying crystallization and prolonging supersaturation duration, with their effectiveness ranked from greatest to least as HPMC E15 > HPMC E5 > HPMC K100-LV > L-HPC > MC. Decreased polymer amount, lower ionic strength, or higher polymer viscosity tended to decrease dissolution/solubility and promote crystal growth to accelerate crystallization. HPMC E15 achieved greatest extended API dissolution and maintenance of supersaturation from a supersaturated state; this polymer thus had the greatest potential for maintaining sustainable API absorption within biologically relevant time frames.

[Research on whole blending end-point evaluation method of Angong Niuhuang Wan based on QbD concept].

The blending end-point determination of Angong Niuhuang Wan (AGNH) is a key technology problem. The control strategy based on quality by design (QbD) concept proposes a whole blending end-point determination method, and provides a methodology for blending the Chinese materia medica containing mineral substances. Based on QbD concept, the laser induced breakdown spectroscopy (LIBS) was used to assess the cinnabar, realgar and pearl powder blending of AGNH in a pilot-scale experiment, especially the whole blending end-point in this study. The blending variability of three mineral medicines including cinnabar, realgar and pearl powder, was measured by moving window relative standard deviation (MWRSD) based on LIBS. The time profiles of realgar and pearl powder did not produce consistent results completely, but all of them reached even blending at the last blending stage, so that the whole proposal blending end point was determined. LIBS is a promising Process Analytical Technology (PAT) for process control. Unlike other elemental determination technologies such ICP-OES, LIBS does not need an elaborate digestion procedure, which is a promising and rapid technique to understand the blending process of Chinese materia medica (CMM) containing cinnabar, realgar and other mineral traditional Chinese medicine. This study proposed a novel method for the research of large varieties of traditional Chinese medicines..

Infrared images of the transiting disk in the epsilon Aurigae system.

Epsilon Aurigae (epsilon Aur) is a visually bright, eclipsing binary star system with a period of 27.1 years. The cause of each 18-month-long eclipse has been a subject of controversy for nearly 190 years because the companion has hitherto been undetectable. The orbital elements imply that the opaque object has roughly the same mass as the visible component, which for much of the last century was thought to be an F-type supergiant star with a mass of approximately 15M[symbol:see text] (M[symbol:see text], mass of the Sun). The high mass-to-luminosity ratio of the hidden object was originally explained by supposing it to be a hyperextended infrared star or, later, a black hole with an accretion disk, although the preferred interpretation was as a disk of opaque material at a temperature of approximately 500 K, tilted to the line of sight and with a central opening. Recent work implies that the system consists of a low-mass (2.2M[symbol:see text]-3.3M[symbol:see text]) visible F-type star, with a disk at 550 K that enshrouds a single B5V-type star. Here we report interferometric images that show the eclipsing body moving in front of the F star. The body is an opaque disk and appears tilted as predicted. Adopting a mass of 5.9M[symbol:see text] for the B star, we derive a mass of approximately (3.6 +/- 0.7)M[symbol:see text] for the F star. The disk mass is dynamically negligible; we estimate it to contain approximately 0.07M[symbol:see text] (M[symbol:see text], mass of the Earth) if it consists purely of dust.

[Application of fast-track surgery concept in the perioperative nursing care of andrological patients: A randomized controlled study].

OBJECTIVE: To evaluate the application of the fast-track surgery (FTS) concept in the nursing care of andrological patients during the perioperative period. METHODS: A total of 200 males to be treated by andrological surgery were included in a control group and another 200 in an observation group, the former received conventional perioperative nursing care, while the latter underwent an FTS nursing care procedure including a variety of proven effective methods to reduce surgical stress and achieve a quick recovery during the perioperative period. Comparisons were made between the two groups of patients in the postoperative enterokinesia time, anal exhaust time, eating time, off-bed time, defecating time, bowel preparation complications, and degree of comfort and satisfaction. RESULTS: Compared with the controls, the patients in the observation group showed significantly earlier postoperative enterokinesia time (ï¼»5.8±0.9ï¼½ vs ï¼»4.4±1.4ï¼½ h, P<0.01), anal exhaust time (ï¼»10.8±1.8ï¼½ vs ï¼»7.7±2.0ï¼½ h, P<0.01), eating time (ï¼»12.9±0.7ï¼½ vs ï¼»6.3±0.7ï¼½ h, P<0.01), off-bed time ï¼»14.3±2.7ï¼½ vs ï¼»8.2±1.4ï¼½ h, P<0.01), and defecating time (ï¼»49.2±2.6ï¼½ vs ï¼»39.6±2.5ï¼½ h, P<0.01), a lower incidence of bowel preparation complications (P<0.01), and a higher degree of comfort (P<0.01) and satisfaction (ï¼»97.5±0.7ï¼½% vs ï¼»99.4±+0.3ï¼½ %, P<0.01). CONCLUSIONS: The FTS concept can be safely and effectively applied to the perioperative nursing care of andrological patients to achieve a faster recovery and higher degree of comfort and satisfaction postoperatively.

[Aging-related change of erectile function and the expression of SIRT1].

OBJECTIVE: To explore aging-related changes in erectile function and the expressions of SIRT1 and other relevant factors in rats. METHODS: We divided 40 male SD rats into four age groups of equal number: 2-month-old (2 mo), 8-month-old (8 mo), 14-month-old (14 mo), and 20-month-old (20 mo), measured the intracavernous pressure (ICP), mean arterial pressure (MAP), and ICP/MAP ratio by electrostimulation of the cavernous nerve, evaluated fibrosis in the corpus cavernosum by Masson's trichrome staining, detected the expressions of SIRT1, P53, and FOXO3a by Western blot, and determined the levels of NO and cGMP using the NO/cGMP kit. RESULTS: Both the ICP/MAP ratio and the cGMP level were elevated with aging, reaching the peak at 8 months and then gradually decreased. Masson staining showed an aging-related increase of collagen fibers in the corpus cavernosum.The expression of SIRT1 was reduced while those of P53 and FOXO3a increased with aging. CONCLUSIONS: Aging-related erectile dysfunction may be attributed to the reduced activity of the NO/cGMP pathway, apoptosis and oxidative stress, and SIRT1 may play a role in aging-related erectile dysfunction.

EGFR-independent autophagy induction with gefitinib and enhancement of its cytotoxic effect by targeting autophagy with clarithromycin in non-small cell lung cancer cells.

Gefitinib (GEF), an inhibitor for EGFR tyrosine kinase, potently induces autophagy in non-small cell lung cancer (NSCLC) cell lines such as PC-9 cells expressing constitutively activated EGFR kinase by EGFR gene mutation as well as A549 and H226 cells with wild-type EGFR. Unexpectedly, GEF-induced autophagy was also observed in non-NSCLC cells such as murine embryonic fibroblasts (MEF) and leukemia cell lines K562 and HL-60 without EGFR expression. Knockout of EGFR gene in A549 cells by CRISPR/Cas9 system still exhibited autophagy induction after treatment with GEF, indicating that the autophagy induction by GEF is not mediated through inhibiting EGFR kinase activity. Combined treatment with GEF and clarithromycin (CAM), a macrolide antibiotic having the effect of inhibiting autophagy flux, enhances the cytotoxic effect in NSCLC cell lines, although treatment with CAM alone exhibits no cytotoxicity. GEF treatment induced up-regulation of endoplasmic reticulum (ER)-stress related genes such as CHOP/GADD153 and GRP78. Knockdown of CHOP in PC-9 cells and Chop-knockout MEF both exhibited less sensitivity to GEF than controls. Addition of CAM in culture medium resulted in further pronounced GEF-induced ER stress loading, while CAM alone exhibited no effect. These data suggest that GEF-induced autophagy functions as cytoprotective and indicates the potential therapeutic possibility of using CAM for GEF therapy. Furthermore, it is suggested that the intracellular signaling for autophagy initiation in response to GEF can be completely dissociated from EGFR, but unknown target molecule(s) of GEF for autophagy induction might exist.

Non-hormonal targets underlying endometriosis: A focus on molecular mechanisms.

Endometriosis is regarded as a hormone-dependent disease. Current therapeutic approaches to treating this common gynecological disorder mainly depend on surgical and hormonal interventions, but the high rate of disease recurrence as well as the side effects related to such therapies make it difficult for patients to recover completely. Molecular evidence has recently suggested that the source of endometriosis can be both hormone-dependent and influenced by the dysregulation of some signaling cascades. In this review, we focus on the non-hormonal triggers of endometriosis and the pre-clinical compounds designed to correct these signaling defects in order to achieve a better understanding of the disease as well as novel approaches to treating it.

Characterization of the antigenicity of Cpl1, a surface protein of Cryptococcus neoformans var. neoformans.

Cryptococcus neoformans var. neoformans is an important fungal pathogen. The capsule is a well established virulence factor and a target site for diagnostic tests. The CPL1 gene is required for capsular formation and virulence. The protein product Cpl1 has been proposed to be a secreted protein, but the characteristics of this protein have not been reported. Here we sought to characterize Cpl1. Phylogenetic analysis showed that the Cpl1 of C. neoformans var. neoformans and the Cpl1 orthologs identified in C. neoformans var. grubii and C. gattii formed a distinct cluster among related fungi; while the putative ortholog found in Trichosporon asahii was distantly related to the Cryptococcus cluster. We expressed Cpl1 abundantly as a secreted His-tagged protein in Pichia pastoris. The protein was used to immunize guinea pigs and rabbits for high titer mono-specific polyclonal antibody that was shown to be highly specific against the cell wall of C. neoformans var. neoformans and did not cross react with C. gattii, T. asahii, Aspergillus spp., Candida spp. and Penicillium spp. Using the anti-Cpl1 antibody, we detected Cpl1 protein in the fresh culture supernatant of C. neoformans var. neoformans and we showed by immunostaining that the Cpl1 protein was located on the surface. The Cpl1 protein is a specific surface protein of C. neoformans var. neoformans.

Establishment and maintenance of a standardized glioma tissue bank: Huashan experience.

Cerebral glioma is the most common brain tumor as well as one of the top ten malignant tumors in human beings. In spite of the great progress on chemotherapy and radiotherapy as well as the surgery strategies during the past decades, the mortality and morbidity are still high. One of the major challenges is to explore the pathogenesis and invasion of glioma at various "omics" levels (such as proteomics or genomics) and the clinical implications of biomarkers for diagnosis, prognosis or treatment of glioma patients. Establishment of a standardized tissue bank with high quality biospecimens annotated with clinical information is pivotal to the solution of these questions as well as the drug development process and translational research on glioma. Therefore, based on previous experience of tissue banks, standardized protocols for sample collection and storage were developed. We also developed two systems for glioma patient and sample management, a local database for medical records and a local image database for medical images. For future set-up of a regional biobank network in Shanghai, we also founded a centralized database for medical records. Hence we established a standardized glioma tissue bank with sufficient clinical data and medical images in Huashan Hospital. By September, 2013, tissues samples from 1,326 cases were collected. Histological diagnosis revealed that 73 % were astrocytic tumors, 17 % were oligodendroglial tumors, 2 % were oligoastrocytic tumors, 4 % were ependymal tumors and 4 % were other central nervous system neoplasms.

[Development and Evaluation of GS-SF for Gastric Stuffiness (Wei PI) Patients Based on Item Response Theory, Computerized Adaptive Testing, and Data Simiuation].

OBJECTIVE: To develop and evaluate the short version of patient reported outcomes (PROs) questionnaire for gastric stuffiness (Wei Pi) patients with modern test theory and technologies, hoping to provide testing tools for related clinical practice and scientific researches with higher quality and less administrative and response burdens. METHODS: Using descriptive study design, clinical data were collected with sociological questionnaire and previous developed full items version of PROs instrument for gastric stuffiness (Wei Pi) patients via field and online surveys between Sep 2011 and Mar 2012. The statistical analysis group identified the termination parameters firstly, and then selected items with discrimination, fitting residual, item information curve (IIC) , item characteristic curve (ICC), and the rank of computerized adaptive testing (CAT) select proportion, etc. After assumption evaluation of item response theory (IRT), IIC, ICC, difficulty coefficient distribution, items-response relation and thresholds, etc. were used for psychometric evaluation of instrument. RESULTS: A total of 331 patients [Ages: 31.99 +/- 10.29 yrs; Male: 186 (56.3%)] were enrolled in statistical analysis. The test termination criterion was Max SE = 0.2 or Max items number =16. After items selection, a 15-item short version of instrument, which contains symptoms facet (8 items) and impact facet (7 items) was generated. With good unidimensionality, local independence, and monotonicity, the IC and ICC in IRT analysis showed good working capability of the questionnaire. The difficulty coefficient distribution and items-response relation were also rational, as well as response thresholds. CONCLUSIONS: The short version of PROs instrument for adult gastric stuffiness (Wei Pi) patients was successfully developed and assessed. The instrument with good methodological and reporting quality could be used in clinical and scientific evaluating their symptoms and impact.

A unique and conserved neutralization epitope in H5N1 influenza viruses identified by an antibody against the A/Goose/Guangdong/1/96 hemagglutinin.

Despite substantial efforts to control and contain H5N1 influenza viruses, bird flu viruses continue to spread and evolve. Neutralizing antibodies against conserved epitopes on the viral hemagglutinin (HA) could confer immunity to the diverse H5N1 virus strains and provide information for effective vaccine design. Here, we report the characterization of a broadly neutralizing murine monoclonal antibody, H5M9, to most H5N1 clades and subclades that was elicited by immunization with viral HA of A/Goose/Guangdong/1/96 (H5N1), the immediate precursor of the current dominant strains of H5N1 viruses. The crystal structures of the Fab' fragment of H5M9 in complexes with H5 HAs of A/Vietnam/1203/2004 and A/Goose/Guangdong/1/96 reveal a conserved epitope in the HA1 vestigial esterase subdomain that is some distance from the receptor binding site and partially overlaps antigenic site C of H3 HA. Further epitope characterization by selection of escape mutants and epitope mapping by flow cytometry analysis of site-directed mutagenesis of HA with a yeast cell surface display identified four residues that are critical for H5M9 binding. D53, Y274, E83a, and N276 are all conserved in H5N1 HAs and are not in H5 epitopes identified by other mouse or human antibodies. Antibody H5M9 is effective in protection of H5N1 virus both prophylactically and therapeutically and appears to neutralize by blocking both virus receptor binding and postattachment steps. Thus, the H5M9 epitope identified here should provide valuable insights into H5N1 vaccine design and improvement, as well as antibody-based therapies for treatment of H5N1 infection.

Diffusion tensor magnetic resonance imaging for predicting the consistency of intracranial meningiomas.

BACKGROUND: The ability of preoperative MRI-sequences to predict the consistency of intracranial meningiomas has not yet been clearly defined. We aim to demonstrate that diffusion tensor imaging (DTI) improves the prediction of intracranial meningiomas consistency. METHODS: We prospectively studied 110 meningioma patients operated on in a single center from March 1st to the 25th of May 2012. Demographic data, location and size of the tumor, peritumoral edema, T1WI, T2WI, proton density weighted (PDWI), fluid-attenuated inversion recover (FLAIR) sequences, and arterial spin labeling (ASL) perfusion were studied and compared with the gray matter signal to predict meningioma consistency. Diffusion tensor imaging (DTI) with fractional anisotropy (FA) and mean diffusivity (MD) maps were included in the preoperative MRI. Meningioma consistency was evaluated by the operating surgeon who was unaware of the neuroradiological findings. RESULTS: In univariate analysis, meningioma size (diameter > 2 cm) and supratentorial or sphenoidal wing location were more frequently associated with hard-consistency meningiomas (p < 0.05). In addition, isointense signal on MD maps (p = 0.009), hyperintense signal on FA maps, and FA value > 0.3 (p = 0.00001) were associated with hard-consistency tumors. Age and sex, T1WI, T2WI, PDWI, FLAIR, or ASL perfusion sequences and peritumoral edema were not significantly associated with meningioma consistency. In logistic regression analysis, the most accurate model (AUC: 0.9459) for predicting a hard-consistency meningioma shows that an isointense signal in MD-maps, a hyperintense signal in FA-maps, and an FA value of more than 0.3 have a significant predictive value. CONCLUSIONS: FA value and MD and FA maps are useful for prediction of meningioma consistency and, therefore, may be considered in the preoperative routine MRI examination of all patients with intracranial meningiomas.