Depth-Guided Bilateral Grid Feature Fusion Network for Dehazing.

In adverse foggy weather conditions, images captured are adversely affected by natural environmental factors, resulting in reduced image contrast and diminished visibility. Traditional image dehazing methods typically rely on prior knowledge, but their efficacy diminishes in practical, complex environments. Deep learning methods have shown promise in single-image dehazing tasks, but often struggle to fully leverage depth and edge information, leading to blurred edges and incomplete dehazing effects. To address these challenges, this paper proposes a deep-guided bilateral grid feature fusion dehazing network. This network extracts depth information through a dedicated module, derives bilateral grid features via Unet, employs depth information to guide the sampling of bilateral grid features, reconstructs features using a dedicated module, and finally estimates dehazed images through two layers of convolutional layers and residual connections with the original images. The experimental results demonstrate the effectiveness of the proposed method on public datasets, successfully removing fog while preserving image details.

Both HuR and miR-29s regulate expression of CB1 involved in infiltration of bone marrow monocyte/macrophage in chronic liver injury.

Bone marrow-derived monocytes/macrophages (BMMs) play a vital role in liver inflammation and fibrogenesis. Cannabinoid receptor 1 (CB1) mediates the recruitment of BMMs into the injured liver. In this study, we revealed the molecular mechanisms under CB1-mediated BMM infiltration. Carbon tetrachloride (CCl4 ) was employed to induce mouse liver injury. In vivo, human antigen R (HuR) was upregulated in macrophages of injured liver. HuR messenger RNA (mRNA) expression was positively correlated with CB1 and F4/80 mRNA expression. Furthermore, we detected the binding between HuR and CB1 mRNA in CCl4 -treated livers. In vitro, HuR modulated arachidonyl-2'-chloroethylamide (ACEA, CB1 agonist)-induced BMM migration by regulating CB1 expression. HuR promoted CB1 expression via binding to CB1 mRNA. ACEA promoted the association between HuR and CB1 mRNA via inducing HuR nucleoplasmic transport. In the cytoplasm, HuR competed with the miR-29 family to improve CB1 expression and BMM migration. In conclusion, our results prove that HuR regulates CB1 expression and influences ACEA-induced BMM migration by competing with miR-29 family.

Assembly of pigeon circovirus-like particles using baculovirus expression system.

Pigeon circovirus (PiCV) is able to infect racing and meat pigeons of all ages and is a key factor that triggers young pigeon disease syndrome (YPDS). PiCV vaccine research has been impeded because PiCV cannot be grown or propagated in cell cultures. Virus-like particles (VLPs), which can be generated by a wide range of expression systems, have been shown to have outstanding immunogenicity and constitute promising vaccines against a wide range of pathogens. Cap protein, which contains neutralizing antibody epitopes, is the only capsid protein of PiCV. In this study, the baculovirus expression system was utilized to express the PiCV Cap protein, which was self-assembled into VLPs with a spherical morphology and diameters of 15-18 nm. Specific antibodies against the Cap protein were induced after BALB/c mice immunized intramuscularly (i.m.) with VLPs combined with adjuvant. Based on these findings, PiCV VLPs may be a promising candidate vaccine against PiCV.

Fusion and hemagglutinin proteins of canine distemper virus promote osteoclast formation through NF-κB dependent and independent mechanisms.

Paget's disease (PD) features abnormal osteoclasts (OC) which sharply increase in number and size and then intensely induce bone resorption. The purpose of this study was to determine the direct effects of canine distemper virus (CDV) and its fusion protein and hemagglutinin protein (F + H) on receptor activator of nuclear factor kappa-B ligand (RANKL) induced OC formation in vitro. Immunofluorescence assay, OC morphological and functional detection, intracellular signaling pathway detection, Real-time PCR analysis and ELISA were applied in this study. Immunofluorescence assay provided the conclusive proof that CDV can infect and replicate in RAW264.7 mouse monocyte cell line, primary human peripheral blood mononuclear cells (PBMC) and their further fused OC. Both CDV and F + H significantly promoted OC formation and bone resorption ability induced by RANKL. Meanwhile, intracellular signaling transduction analysis revealed CDV and F + H specifically upregulated the phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) induced by RANKL, respectively. Furthermore, without RANKL stimulation, both CDV and F + H slightly induced OC-like cells formation in RAW264.7 cell line even in the presence of NF-κB inhibitor. F + H upregulate OC differentiation and activity through modulation of NF-κB signaling pathway, and induce OC precursor cells merging dependent on the function of glycoproteins themselves. These results meant that F and H proteins play a pivotal role in CDV supporting OC formation. Moreover, this work further provide a new research direction that F and H proteins in CDV should be considered as a trigger during the pathogenesis of PD.

Efficacy and safety of a novel acetylcholinesterase inhibitor octohydroaminoacridine in mild-to-moderate Alzheimer's disease: a Phase II multicenter randomised controlled trial.

Background: inhibition of acetylcholinesterase (AChE) has been a effective treatment for Alzheimer's disease (AD). Octohydroaminoacridine, a new AChE inhibitor, is a potential treatment for AD. Method: we conducted a multicenter, randomised, double blind, placebo-controlled, parallel-group Phase II clinical trial to investigate the effects of octohydroaminoacridine in patients with mild-to-moderate AD. Patients were randomised to receive placebo thrice daily, octohydroaminoacridine 1 mg/thrice daily (TID) (low-dose group), 2 mg/TID (middle-dose group) or 4 mg/TID (high-dose group). Doses in the middle-dose and high-dose group were titrated over 2-4 weeks. Changes from baseline to Week 16 were assessed with the AD Assessment Scale-Cognitive Subscale (ADAS-cog), Clinician's Interview-Based Impression of Change Plus (CIBIC+), activities of daily living (ADL) and the neuropsychiatric inventory (NPI). ADAS-cog was the primary end point of the study. A two-way analysis of covariance and least squares mean t-test were used. Results: at Week 16, the changes from baseline in ADAS-cog were 1.4, -2.1, -2.2 and -4.2 for placebo, low-, middle- and high-dose groups, respectively. Patients in the high-dose group had better performance in CIBIC+ and ADL scores at the end of the study. There was no significant difference in the change in NPI score among the groups. The effects of octohydroaminoacridine were dose dependent, and were effective within 16 weeks of treatment. No evidence was found for more adverse events that occurred in different drug groups than placebo group. Conclusions: octohydroaminoacridine significantly improved cognitive function and behaviour in patients with mild-to-moderate AD and this effect was dose dependent.

An observational clinical and video-polysomnographic study of the effects of rotigotine in sleep disorder in Parkinson's disease.

PURPOSE: Sleep disturbance is common in Parkinson's disease (PD) and negatively impacts quality of life. There is little data on how dopamine agonists influence nocturnal sleep in PD, particularly in sleep laboratory data to measure sleep parameters and their changes objectively. The goal of this open-label study was to objectively evaluate the effect of rotigotine on sleep in PD patients by video-polysomnographic methods. METHODS: A total of 25 PD patients with complaints of nocturnal sleep impairment were enrolled. The sleep quality before and after stable rotigotine therapy was evaluated subjectively through questionnaire assessments and objectively measured by video-polysomnographic methods. The Parkinsonism, depression, anxiety, and quality of life of PD patients were also evaluated through questionnaire assessments. RESULTS: At the end of rotigotine treatment, the PD daytime functioning, motor performance, depression, subjective quality of sleep, and the quality of life improved. Video-polysomnographic analysis showed that the sleep efficiency and stage N1% were increased, while the sleep latency, wake after sleep onset, and the periodic leg movements in sleep index were decreased after rotigotine treatment. CONCLUSIONS: Video-polysomnographic analysis confirmed the subjective improvement of sleep after rotigotine treatment. This observation suggests that in PD rotigotine is a treatment option for patients complaining from sleep disturbances.

Emergency preparedness for mass gatherings: Lessons of "12.31" stampede in Shanghai Bund.

According to WHO, one of these mass gatherings with critical risk is stampedes. Shanghai "12.31" stampede was a preventable tragedy that the government and event planner hold responsibility for. At the same time, it can be a legacy for improvement in the future. The government should draw experience on the implementation of an emergency preparedness system, in order to improve the rapid emergency response during mass gatherings in the future.

Low-Dose Atypical Antipsychotic Risperidone Improves the 5-Year Outcome in Alzheimer's Disease Patients with Sleep Disturbances.

Sleep disturbances (SD) accelerate the progression of Alzheimer's disease (AD) and increase the stress of caregivers. However, the long-term outcome of disturbed nocturnal sleep/wake patterns in AD and on increased stress of spousal caregivers is unclear. This study assessed the 5-year effect of nocturnal SD on the long-term outcome in AD patients. A total of 156 donepezil-treated mild-moderate AD patients (93 AD + SD and 63 AD - SD as a control group) were recruited. The AD + SD patients were formed into 4 subgroups according to the preferences of spousal caregivers for treatment with atypical antipsychotics (0.5-1 mg risperidone, n = 22), non-benzodiazepine hypnotic (5-10 mg zolpidem tartrate, n = 33), melatonin (2.55 mg, n = 9), or no-drug treatment (n = 29). SD were evaluated by polysomnography, sleep scale, and cognitive scale examinations. Moreover, all spousal caregivers of AD patients were assessed using a series of scales, including sleep, anxiety, mood, and treatment attitude scales. Our data showed that nocturnal sleep/wake disturbances were significantly associated with lower 5-year outcomes for AD patients, earlier nursing home placement, and more negative emotions of spousal caregivers. Treatment with low-dose atypical antipsychotic risperidone improved the 5-year outcome in AD + SD patients. In conclusion, low-dose atypical antipsychotic risperidone improves the 5-year outcome in AD patients with SD. Moreover, improvement of nocturnal sleep problems in AD patients will also bring better emotional stability for AD caregivers.

Functional Magnetic Resonance Imaging Study of Apathy in Alzheimer's Disease.

An fMRI study was launched to understand mechanisms of Alzheimer's disease (AD) patients with apathy. The authors reviewed 7 AD patients with apathy and 6 AD patients without apathy. The block method was adopted, and 24 pictures representing positive, negative, and neutral emotional stimuli were viewed when patients were given brain fMRI. Under "sad versus neutral" stimulation, non-apathetic AD patients had increased activity in bilateral amygdala and bilateral fusiform gyrus, whereas apathetic AD patients only had increased activities in bilateral fusiform gyrus. Thus, the amygdala was the possible anatomical structure related to apathy in AD patients.

[Management of bilateral benign paroxysmal positional vertigo with Dix-Hallpike test].

OBJECTIVE: To explore the diagnosis and treatment of benign paroxysmal positional vertigo (BPPV) with bilateral positive Dix-Hallpike test. METHODS: This is a retrospective study based on the clinical data of BPPV patients diagnosed in the Dizziness Clinic of Changzheng Hospital from January 2012 to December 2012. Totally 490 patients with vertigo and nystagmus provoked by Dix-Hallpike maneuver were included in the present analysis. RESULTS: Among all the patients, 55 (11.2%) of them presented with bilateral nystagmus by the provocative test. According to the type of nystagmus provoked by Dix-Hallpike maneuver, the 55 patients can be divided into the following four categories. (1) Bilateral geotropic (n = 16) and apogeotropic nystagmus (n = 5): all these patients were diagnosed with horizontal canal BPPV and free of vertigo after head side-shaking exercise in supine position and Barbecue maneuver. (2) Bilateral predominant down-beating nystagmus (n = 2): patients in this group were diagnosed with anterior canal BPPV, and got recovered after Kim maneuver. (3) Bilateral torsional up-beating geotropic nystagmus (n = 20): after a lying-down test, 6 of the patients manifested as vertical up-beating nystagmus and 14 patients remained torsional up-beating nystagmus. The former were diagnosed with bilateral posterior canal BPPV, and were cured after bilateral PRM therapy, and the latter were diagnosed with horizontal canal BPPV, who were cured after Barbecue maneuver. (4) Torsional up-beating geotropic nystagmus on one side and down-beating nystagmus on the other side (n = 12). The down-beating nystagmus on the other side disappeared when the patients was firstly seated up with head down in 30 degrees for half an hour before second Dix-Hallpike maneuver. These patients were diagnosed with unilateral posterior canal BPPV and cured by PRM therapy. CONCLUSIONS: It is common for vertigo patients with bilateral nystagmus induced by Dix-Hallpike test. The diagnoses should be made by the types of nystagmus provoked step by step before maneuver therapy.

[The association of duration of hypertension and changes in cognitive function in hypertension patients].

OBJECTIVE: To investigate the relationship between duration of hypertension and cognitive function in adult hypertension patients. METHODS: A total of 224 subjects with normal blood pressure were enrolled in group A, and 1 296 patients with poorly controlled hypertension were further divided by the duration of hypertension into group B ( ≤ 5 years), group C (6-10 years), group D (11-20 years) and group E (> 20 years). Face-to-face surveys were conducted in all the subjects by trained physicians using Mini-Mental-State-Examination (MMSE) and Clock-Drawing-Test (CDT). The incidences of cognitive impairment were compared among the five groups and the relationship between duration of hypertension and cognitive function were analyzed by SPSS 18.0 software. RESULTS: (1)Compared with the normotensive group, the hypertensive group performed worse in the scores of MMSE, CDTs, the memory type cognitive function and the non-memory type cognitive function (MMSE:Z = -2.585, P = 0.010; CDTs:Z = -3.689, P < 0.001; memory type cognitive function:Z = -2.718, P = 0.007; non-memory type cognitive function: Z = -1.994, P = 0.046). (2) The incidences of cognitive impairment in the five groups were 3.6% (8/224), 6.6% (26/393), 16.6% (72/433), 19.7% (55/279) and 33.5% (64/191), respectively. (3) Compared with the group A, the cognitive function was significantly worse in the group E (MMSE:Z = 61.314, P < 0.001; CDTs: Z = 44.642, P < 0.001; memory type cognitive function:Z = 35.703, P < 0.001; non-memory type cognitive function:Z = 54.440, P < 0.001). CONCLUSIONS: Hypertension is a risk factor for the cognitive dysfunction. The incidence of cognitive dysfunction and the severity are positively associated with the duration of hypertension. In those with hypertension over 20 years, the cognitive dysfunction occurs much more obviously.

Adenovirus type 5-expressing Gn induces better protective immunity than Gc against SFTSV infection in mice.

Severe fever with thrombocytopenia syndrome (SFTS) is caused by the SFTS virus (SFTSV) with high morbidity and mortality. The major immunodominant region of SFTSV surface glycoprotein (G) remains unclear. In this study, we constructed adenovirus type 5 (Ad5) vectored vaccine candidates expressing different regions of SFTSV G (Gn, Gc and Gn-Gc) and evaluated their immunogenicity and protective efficacy in mice. In wild-type mice, compared with Ad5-Gc or Ad5-Gn-Gc, Ad5-Gn recruited/activated more dendritic cells and B cells in lymph nodes or peripheral blood, causing Th1-/Th2-mediated responses in splenocytes and triggered a greater level of SFTSV-neutralizing antibodies. In IFNAR Ab-treated mice, immunization of Ad5-Gn exhibited better protection against SFTSV challenge than Ad5-Gc or Ad5-Gn-Gc. Furthermore, passive immunization revealed complete protective immunity of Gn-specific serum rather than Gc. Collectively, our data demonstrated that Gn is the immunodominant fragment of SFTSV G and could be a potential candidate for SFTSV vaccine development.

Efficacy and safety of Dimdazenil in the adult insomnia patients: a phase II randomized, multicenter, double-blind, placebo-controlled, and parallel-group study.

STUDY OBJECTIVES: To evaluate the efficacy and safety of Dimdazenil, a positive allosteric modulator with selectivity for α1, α5 subunit-containing GABAA receptors, on sleep variables in patients with insomnia disorder. METHODS: In this randomized, double-blind, placebo-controlled trial, adults (18-65 years) with insomnia disorder were randomized (1:1:1:1 to receive daily oral placebo, Dimdazenil (1.5, 2.5, or 5 mg) for 14 days. The primary efficacy outcome was the total sleep time (TST) on day 1/2 and day 13/14, measured by polysomnography. The secondary outcome measures included (1) latency to persistent sleep (LPS), sleep efficiency (SE), wake after sleep onset (WASO) and number of awakenings (NAW) on days 1/2 and day 13/14, and (2) the average subjective sleep latency (sSL), total sleep time (sTST), wake after sleep onset (sWASO) and number of awakenings (sNAW) recorded in sleep diary and sleep questionnaire, and the evaluation of insomnia severity index. Rebound insomnia, withdrawal, and treatment-emergent adverse events were also assessed. RESULTS: Of 569 patients screened, 288 (76.4% female) were randomized and received one dose. For the primary outcomes, TST was significantly improved in the Dimdazenil 1.5, 2.5, and 5 mg group compared with the placebo group at day 1/2, and significantly improved in the Dimdazenil 2.5 and 5 mg groups compared with the placebo group at day 13/14. The Least Squares Means (standard errors) and 95% Confidence Intervals for the three active doses compared to placebo are 25.5 (8.31), (9.16, 41.89) for the 1.5 mg dose; 17.4 (8.19), (1.29, 33.55) for the 2.5 mg dose; 22.8 (8.15), (6.72, 38.80) for the 5 mg dose on day 1/2. Corresponding data on day 13/14 are 7.6 (8.07), (-8.24, 23.53) and 19.3 (8.06), (3.43, 35.17) and 18.2 (7.95), (2.49, 33.80). LPS was significantly reduced in the Dimdazenil 5 mg group compared with the placebo group on day 1/2. SE was significantly improved in the Dimdazenil 1.5 and 5 mg group compared with the placebo group at day 1/2. In the subjective sleep parameters, sSL on average was significantly lower in the Dimdazenil 1.5, 2.5, and 5 mg groups compared with the placebo group. sTST on average was significantly higher in the Dimdazenil 1.5, 2.5, and 5 mg groups compared with the placebo group. The most common TEAEs were dizziness, vertigo, and weakness with no clinically relevant treatment-related serious adverse events. CONCLUSIONS: Dimdazenil of 1.5, 2.5, and 5 mg improved certain objective and subjective sleep outcomes in people with insomnia disorder, with a favorable safety profile. These findings suggested that Dimdazenil may represent a promising new treatment for insomnia disorder, a prevalent condition with limited effective and safe treatments available. CLINICAL TRIAL INFORMATION: A multicenter, randomized, double-blind, multidose, placebo parallel controlled phase II clinical study of EVT201 in the treatment of insomnia disorders (http://www.chinadrugtrials.org), with the number of CTR20150664.

SFTSV nucleoprotein mediates DNA sensor cGAS degradation to suppress cGAS-dependent antiviral responses.

Cyclic GMP-AMP synthase (cGAS) is an important DNA pattern recognition receptor that senses double-stranded DNA derived from invading pathogens or self DNA in cytoplasm, leading to an antiviral interferon response. A tick-borne Bunyavirus, severe fever with thrombocytopenia syndrome virus (SFTSV), is an RNA virus that causes a severe emerging viral hemorrhagic fever in Asia with a high case fatality rate of up to 30%. However, it is unclear whether cGAS interacts with SFTSV infection. In this study, we found that SFTSV infection upregulated cGAS RNA transcription and protein expression, indicating that cGAS is an important innate immune response against SFTSV infection. The mechanism of cGAS recognizing SFTSV is by cGAS interacting with misplaced mitochondrial DNA in the cytoplasm. Depletion of mitochondrial DNA significantly inhibited cGAS activation under SFTSV infection. Strikingly, we found that SFTSV nucleoprotein (N) induced cGAS degradation in a dose-dependent manner. Mechanically, N interacted with the 161-382 domain of cGAS and linked the cGAS to LC3. The cGAS-N-LC3 trimer was targeted to N-induced autophagy, and the cGAS was degraded in autolysosome. Taken together, our study discovered a novel antagonistic mechanism of RNA viruses, SFTSV is able to suppress the cGAS-dependent antiviral innate immune responses through N-hijacking cGAS into N-induced autophagy. Our results indicated that SFTSV N is an important virulence factor of SFTSV in mediating host antiviral immune responses. IMPORTANCE: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne RNA virus that is widespread in East and Southeast Asian countries with a high fatality rate of up to 30%. Up to now, many cytoplasmic pattern recognition receptors, such as RIG-I, MDA5, and SAFA, have been reported to recognize SFTSV genomic RNA and trigger interferon-dependent antiviral responses. However, current knowledge is not clear whether SFTSV can be recognized by DNA sensor cyclic GMP-AMP synthase (cGAS). Our study demonstrated that cGAS could recognize SFTSV infection via ectopic mitochondrial DNA, and the activated cGAS-stimulator of interferon genes signaling pathway could significantly inhibit SFTSV replication. Importantly, we further uncovered a novel mechanism of SFTSV to inhibit innate immune responses by the degradation of cGAS. cGAS was degraded in N-induced autophagy. Collectively, this study illustrated a novel virulence factor of SFTSV to suppress innate immune responses through autophagy-dependent cGAS degradation.

Pancreaticobiliary maljunction is associated with common bile duct carcinoma: a meta-analysis.

OBJECTIVE: Pancreaticobiliary maljunction (PBM) has been reported to be associated with an increased risk of gallbladder carcinoma. However, the relationship between PBM and common bile duct carcinoma (CBDC) remains unclear. We aimed to conduct a meta-analysis to determine the available evidence on the association between PBM and CBDC. METHODS: The pooled odds ratio (OR) and standard mean differences (SMD) with 95% confidence interval (95% CI) were used to estimate the effects. RESULTS: A total of eight case-control studies and two cohort studies were identified. The incidence of PBM was higher in CBDC patients than in controls (OR = 1.45; 95% CI, 1.19-1.76). Compared with patients without PBM, CBDC patients with PBM were younger at the diagnosis age (SMD = -0.46; 95% CI, -0.64 to -0.28). A difference in the incidence of associated CDC was found between CBDC patients with or without PBM (OR = 2.14; 95% CI, 1.60-2.87). CONCLUSIONS: Compared with benign biliary tract diseases, the incidence of PBM was higher in CBDC patients, especially in relatively young patients. We also found that the incidence of CDC was higher in CBDC patients with PBM. These findings showed positive association between PBM and CBDC, which may help in identifying high-risk individuals.

Quantification of carboxylate-bridged di-zinc site stability in protein due ferri by single-molecule force spectroscopy.

Carboxylate-bridged diiron proteins belong to a protein family involved in different physiological processes. These proteins share the conservative EXXH motif, which provides the carboxylate bridge and is critical for metal binding. Here, we choose de novo-designed single-chain due ferri protein (DFsc), a four-helical protein with two EXXH motifs as a model protein, to study the stability of the carboxylate-bridged di-metal binding site. The mechanical and kinetic properties of the di-Zn site in DFsc were obtained by atomic force microscopy-based single-molecule force spectroscopy. Zn-DFsc showed a considerable rupture force of ~200 pN, while the apo-protein is mechanically labile. In addition, multiple rupture pathways were observed with different probabilities, indicating the importance of the EXXH-based carboxylate-bridged metal site. These results demonstrate carboxylate-bridged di-metal site is mechanically stable and improve our understanding of this important type of metalloprotein.

Down-regulating insulin-like growth factor-1 receptor reduces amyloid-ß deposition in mice cortex induced by chronic sleep restriction.

OBJECTIVE: Insufficient sleep affects cognitive function, but the underlying mechanism and potential protective ways are yet to be fully understood. This study aimed to explore the influence of chronic sleep restriction (CSR) on the insulin-like growth factor-1 (IGF-1) signaling pathway, and whether down-regulating IGF-1 signaling pathway would modulate amyloid-ß (Aß) peptides metabolism and its cortical deposition after CSR. Methods 8-week IGF-1R+/- mice and wild-type (WT) C57BL/6 (C57) mice were divided into four groups: IGF-1R+/- CSR (MUSR), IGF-1R+/- control (MUCO), C57 CSR (C57SR) and C57 control (C57CO). CSR model was established by application of slowly rotating drum for 2 months. Body weight and Lee's index were measured. The level of IGF-1 in plasma was measured by enzyme linked immunosorbent assay (ELISA). Aß accumulation was detected by immunofluorescence. The expressions of amyloid precursor protein (APP), ß-site amyloid precursor protein-cleaving enzyme-1 (BACE-1) and C99 were detected using western-blot (WB). Results Two-way ANOVA showed genotypic effect was significant on body weight and Lee's index. Neither treatment effect nor interaction reached significant difference on body weight and Lee's index. The level of IGF-1 in plasma was significantly decreased in C57SR compared with C57CO. Besides, compared with C57CO, Aß was markedly accumulated in frontal cortex, in parallel with increased expressions of BACE-1 and C99, and with no difference of APP in C57SR group. Further, no significant changes of Aß, BACE-1, C99 and APP were detected in MUSR compared with MUCO. Conclusions This study showed that CSR could induce the decrease of circulating IGF-1 in mice. By using the IGF-1R+/- mice, we found that down-regulating IGF-1R could reduce Aß deposition in mice frontal cortex after CSR via inhibiting BACE-1 protein expression and activity, which were independent of the changes of body weight and Lee's index. These findings indicate that the blockage of IGF-1 signaling pathway might be a protection mechanism for alleviating the impact of CSR.

Over-expression of IL-33 enhances rabies virus early antigen presentations and cellular immune responses in mice.

Human inactivated rabies virus (RABV) vaccines have been widely used worldwide over 30 years. The mechanisms of humoral immunity elicited by previously reported rabies candidate vaccines have been fully investigated, but little is known about the cellular immunity profiles. Herein, the recombinant RABV rLBNSE-IL-33 overexpressing the mouse interleukin-33 (IL-33) proliferated well in Neuro-2a cells and had no effects with the parent virus on growth kinetic in vitro and viral pathogenicity in mice. The rLBNSE-IL-33 experienced more antigen presentations by MHC-II on DCs and activated more CD4+ T cells which helped recruit more CD19+CD40+ B cells in blood and promote rapid and robust IgG1 antibodies responses at initial infection stage compared with the parent rLBNSE strain. Simultaneously, the rLBNSE-IL-33 were also presented by MHC-I to CD8+ T cells which contributed to produce high levels of IgG2a. The rLBNSE-IL-33 elicited significantly high levels of RABV-specific IFN-γ secreting memory CD4+ T cells, more RABV-specific IL-4 and IFN-γ secreting memory CD8+ T cells in spleens at early infection stage in mice. Altogether, overexpression of IL-33 in rLBNSE-IL-33 enhanced early antigen presentation, markedly promote CD4+, memory CD4+ and CD8+ T cells-mediated responses and provided a 100 % protection from lethal RABV challenge in mice. These findings provided an alternative novel therapy and vaccine strategy in future.

[Analysis of misdiagnosed cases with benign paroxysmal positional vertigo].

OBJECTIVE: To analyze the misdiagnosed cases with benign paroxysmal positional vertigo (BPPV). METHODS: During October 2010 to January 2011, a total of 287 patients with dizziness visited the Dizziness Clinic at Changzheng Hospital, Second Military Medical University. Forty-eight misdiagnosed cases with BPPV were collected and their clinical data were analyzed. All 48 cases were diagnosed by the Dix-Hallpike or Roll test maneuver. RESULTS: (1) CLINICAL FEATURES: there were 38 females and 10 males with an average age of 54 ± 12 years old (range: 31 - 87). Posterior semicircular canal was involved in 75.0% (36/48) whereas the horizontal semicircular and multiple canals in 20.8% (10/48) and 4.2% (2/48) respectively. All patients were treated successfully. And 41 cases (85.4%) were cured on the first visiting day. Recurrences of BPPV occurred in 6 cases during the follow-up. (2) The initial visiting departments consisted of the department of general internal medicine 43.8% (21/48), department of neurology 27.1% (13/48), department of osteology 18.7% (9/48), ear, nose & throat (ENT) department 2.1% (1/48) and other departments 8.3% (4/48). In addition, 68.7% (33/48) of them frequented the general out-patient clinics during their initial visits and the other 31.3% (15/48) used the emergency services. (3) The initial diagnoses included vertebrobasilar insufficiency/cerebral circulation insufficiency 27.1% (13/48), cervical spondylosis 27.1% (13/48), cerebral infarction 4.2% (2/48), Meniere's disease 2.1% (1/48) and others 10.4% (5/48); Besides, 29.1% (14/48) of them had no diagnosis. (4) The average clinic visits per patient were 3.4 times (164 visits/48 cases). (5) The most commonly performed tests included brain computed tomography (CT) (28 person-times), cervical magnetic resonance imaging (MRI) (19 person-times), brain MRI (18 person-times), cervical radiography (18 person-times) and cervical CT (8 person-times). CONCLUSION: In these misdiagnosed cases of BPPV, most of them were middle-aged women. They were most likely to have their first consultations in the departments of general internal medicine and neurology. Therefore these two departments should pay more attention to applying the maneuver of Dix-Hallpike or Roll test so as to reduce the misdiagnosis of BPPV and the waste of healthcare resources.

Pore Structure Characteristics and Controlling Factors of a Tight Sandstone Reservoir in the Paleogene Shahejie Formation, Nanpu Sag, Bohai Bay Basin, China.

Tight sandstone reservoirs have ultralow physical properties and strong heterogeneity, and there is a need to describe the corresponding pore structure characteristics systematically to promote research on unconventional reservoirs. The pore structure, controlled by the diagenesis and volcanic activity of the tight reservoirs in the third member of the Shahejie Formation (Es3) of the Gaoshangpu structural belt in the Nanpu Sag, is studied by high-pressure mercury injection, nuclear magnetic resonance, and constant-rate-controlled mercury porosimetry. The results show that the Es3 reservoir can be divided into three types: the pore radii of Type I reservoirs range from 120 to 180 µm, and the throat radii are larger than 1 µm, resulting in good pore connectivity; pore radii of Type II reservoirs are approximately 100 µm, and the throat radii range from 0.1 to 1 µm, resulting in moderate pore connectivity; and pore radii of Type III reservoirs are much smaller than 100 µm, and the throat radii are smaller than 0.1 µm, resulting in worst pore connectivity. The pore size of Type I reservoirs is most sensitive to compaction, and the pore connectivity is mainly controlled by carbonate cementation; the pore throat size and pore connectivity of Type II reservoirs are seriously affected by clay cementation, and pores are mainly formed by dissolution. However, the pore structure of Type III reservoirs is the worst among those investigated in this study but can be further improved by dissolution to a certain extent. Volcanic activity controls cementation and affects dissolution, thus changing the pore structure. A pore structure evolution model is established, which can provide a reference for future oil gas exploration.