Loss of DJ-1 function contributes to Parkinson's disease pathogenesis in mice via RACK1-mediated PKC activation and MAO-B upregulation.

Parkinson's disease (PD) is a common neurodegenerative motor disorder characterized by a dramatic reduction in pars compacta of substantia nigra dopaminergic neurons and striatal dopamine (DA) levels. Mutations or deletions in the PARK7/DJ-1 gene are associated with an early-onset familial form of PD. DJ-1 protein prevents neurodegeneration via its regulation of oxidative stress and mitochondrial function as well as its roles in transcription and signal transduction. In this study, we investigated how loss of DJ-1 function affected DA degradation, ROS generation and mitochondrial dysfunction in neuronal cells. We showed that loss of DJ-1 significantly increased the expression of monoamine oxidase (MAO)-B but not MAO-A in both neuronal cells and primary astrocytes. In DJ-1-knockout (KO) mice, MAO-B protein levels in the substantia nigra (SN) and striatal regions were significantly increased. We demonstrated that the induction of MAO-B expression by DJ-1 deficiency depended on early growth response 1 (EGR1) in N2a cells. By coimmunoprecipitation omics analysis, we found that DJ-1 interacted with receptor of activated protein C kinase 1 (RACK1), a scaffolding protein, and thus inhibited the activity of the PKC/JNK/AP-1/EGR1 cascade. The PKC inhibitor sotrastaurin or the JNK inhibitor SP600125 completely inhibited DJ-1 deficiency-induced EGR1 and MAO-B expression in N2a cells. Moreover, the MAO-B inhibitor rasagiline inhibited mitochondrial ROS generation and rescued neuronal cell death caused by DJ-1 deficiency, especially in response to MPTP stimulation in vitro and in vivo. These results suggest that DJ-1 exerts neuroprotective effects by inhibiting the expression of MAO-B distributed at the mitochondrial outer membrane, which mediates DA degradation, ROS generation and mitochondrial dysfunction. This study reveals a mechanistic link between DJ-1 and MAO-B expression and contributes to understanding the crosslinks among pathogenic factors, mitochondrial dysfunction and oxidative stress in PD pathogenesis.

Brainstem auditory evoked potential combined with high resolution cranial base CT can optimize the diagnosis of auditory nerve injury.

PURPOSE: Auditory nerve injury is one of the most common nerve injury complications of skull base fractures. However, there is currently a lack of auxiliary examination methods for its direct diagnosis. The purpose of this study was to find a more efficient and accurate means of diagnosis for auditory nerve injury. METHODS: Through retrospectively analyzing the results of brainstem auditory evoked potential (BAEP) and high-resolution CT (HRCT) in 37 patients with hearing impairment following trauma from January 1, 2018 to July 31, 2020, the role of the two inspection methods in the diagnosis of auditory nerve injury was studied. Inclusion criteria were patient had a clear history of trauma and unilateral hearing impairment after trauma; while exclusion criteria were: (1) severe patient with a Glasgow coma scale score ≤5 because these patients were classified as severe head injury and admitted to the intensive care unit, (2) patient in the subacute stage admitted 72 h after trauma, and (3) patient with prior hearing impairment before trauma. According to Goodman's classification of hearing impairment, the patients were divided into low/medium/severe injury groups. In addition, patients were divided into HRCT-positive and negative groups for further investigation with their BAEP results. The positive rates of BEAP for each group were observed, and the results were analyzed by Chi-square test (p < 0.05, regarded as statistical difference). RESULTS: A total of 37 patients were included, including 21 males and 16 females. All of them were hospitalized patients with GCS score of 6-15 at the time of admission. The BAEP positive rate in the medium and severe injury group was 100%, which was significantly higher than that in the low injury group (27.27%) (p < 0.01). The rate of BEAP positivity was significantly higher in the HRCT-positive group (20/30, 66.7%) than in the HRCT-negative group (1/7, 14.3%) (p < 0.05). Twenty patients (54.05%) were both positive for BEAP and HRCT test, and considered to have auditory nerve damage. Six patients (16.22%) were both negative for BEAP and HRCT test, and 10 patients (27.03%) were BAEP-negative but HRCT-positive: all the 16 patients were considered as non-neurological injury. The rest 1 case (2.70%) was BAEP-positive but HRCT-negative, which we speculate may have auditory nerve concussion. CONCLUSION: By way of BAEP combining with skull base HRCT, we may improve the accuracy of the diagnosis of auditory nerve injury. Such a diagnostic strategy may be beneficial to guiding treatment plans and evaluating prognosis.

Selenate and Nitrate Bioreductions Using Methane as the Electron Donor in a Membrane Biofilm Reactor.

Selenate (SeO4(2-)) bioreduction is possible with oxidation of a range of organic or inorganic electron donors, but it never has been reported with methane gas (CH4) as the electron donor. In this study, we achieved complete SeO4(2-) bioreduction in a membrane biofilm reactor (MBfR) using CH4 as the sole added electron donor. The introduction of nitrate (NO3(-)) slightly inhibited SeO4(2-) reduction, but the two oxyanions were simultaneously reduced, even when the supply rate of CH4 was limited. The main SeO4(2-)-reduction product was nanospherical Se(0), which was identified by scanning electron microscopy coupled to energy dispersive X-ray analysis (SEM-EDS). Community analysis provided evidence for two mechanisms for SeO4(2-) bioreduction in the CH4-based MBfR: a single methanotrophic genus, such as Methylomonas, performed CH4 oxidation directly coupled to SeO4(2-) reduction, and a methanotroph oxidized CH4 to form organic metabolites that were electron donors for a synergistic SeO4(2-)-reducing bacterium.

The Loss of a Sugar Chain at C(3) Position Enhances Stemucronatoside K-Induced Apoptosis, Cell Cycle Arrest, and Hedgehog Pathway Inhibition in HT-29 Cells.

Stemucronatoside K (SMK) and its aglycone stephanthraniline A (STA) are the most representative of a series of novel C21 steriodal compounds that we have previously isolated from Asclepiadaceae plants. The objectives of this study were to investigate the antitumor activity of SMK and STA, and clarify the effect of the sugar chain at the C(3) position. Our results showed that both SMK and STA decreased the growth of HT-29 cells in a dose- and time-dependent manner. Meanwhile, STA showed much stronger inhibitory effect than SMK. Treatment of HT-29 cells with STA increased the apoptotic cell numbers and the protein expression of cleaved caspase 3 and cleaved-PARP. G1 phase cell cycle arrest and decreased expression of cyclin D1 and cyclin-dependent kinases 4 were also observed after STA treatment. Furthermore, STA reduced the mRNA levels of four Hedgehog pathway components (GLI1, GLI2, GLI3, and PTCH1) and suppressed Shh-induced Hedgehog pathway activation in a concentration-dependent manner. These results indicated that SMK and STA could inhibit the growth of HT-29 cells by inducing apoptosis, cell cycle arrest, and hedgehog pathway inhibition. The loss of sugar chain at C(3) position could enhance SMK's activity. This study is beneficial to understand the use of natural C21 steroids as antitumor lead compounds.

[Rapid Detection of Adenovirus in Fecal Samples by Capillary Electrophoresis-laser Induced Fluorescence and Microchip Capillary Electrophoresis-laser Induced Fluorescence].

OBJECTIVE: To establish a rapid and sensitive method based on polymerase chain reaction (PCR) combined with capillary electrophoresis-laser induced fluorescence (CE-LIF) and microchip capillary electrophoresis-laser induced fluorescence (MCE-LIF) for detecting adenoviruses in fecal samples. METHODS: The DNA of adenovirus in fecal samples were extracted by the commercial kits and the conserved region of hexon gene was selected as the target gene and amplified by PCR reaction. After labeling highly sensitive nucleic acid fluorescent dye SYBR Gold and SYBR Orange respectively, PCR amplification products were separated by CE and MCE under the optimized condition and detected by LIF detector. RESULTS: PCR amplification products could be detected within 9 min by CE-LIF and 6 min by MCE-LIF under the optimized separation condition. The sequenced PCR product showed good specificity in comparison with the prototype sequences from NCBI. The intraday and inter-day relative standard deviation (RSD) of the size (bp) of the target DNA was in the range of 1.14%-1.34% and 1.27%- 2.76%, respectively, for CE-LIF, and 1.18%-1.48% and 2.85%-4.06%, respectively, for MCE-LIF. The detection limits was 2.33 x 10(2) copies/mL for CE-LIF and 2.33 x 10(3) copies/mL for MCE-LIF. The two proposed methods were applied to detect fecal samples, both showing high accuracy. CONCLUSION: The two proposed methods of PCR-CE-LIF and PCR-MCE-LIF can detect adenovirus in fecal samples rapidly, sensitively and specifically.

[Quality assessment on schisandrae fructus from different habitats].

OBJECTIVE: To assay five lignans in Schisandrae Fructus collected from different habitats. METHODS: HPLC method was developed to assay Schizandrol A, Schizandrol B, Schisantherain A, deoxyschizandrin and gamma-schizandrin in Schisandrae Fructus. Hierarchical clustering analysis (HCA) and principal components analysis (PCA) were performed to evaluate and classify 30 batches of samples based on the contents of the five lignans using SOLO and SPSS 19.0 software. RESULTS: 30 batches of samples were divided into three groups, which reflecting their quality characteristics. CONCLUSION: PCA and HCA provide the basis for the classification and quality evaluation of Schisandrae Fructus. The content analysis provides reference for resources saving and rational using of Schisandrae Fructus.

[Spatiotemporal Differentiation of Carbon Budget and Carbon Compensation Zoning Based on the Plan for Major Function-oriented Zones：A Case Study of Counties in the Yellow River Basin].

Exploring the spatiotemporal differentiation of the carbon budget and clarifying the zoning of carbon compensation based on the perspective of the main function-oriented zones is of great significance for promoting regional low-carbon development and achieving the "dual carbon" goal. This study was conducted using 550 counties in the Yellow River Basin as the basic unit, and based on the concentration index to examine the spatial distribution characteristics of carbon emissions and carbon absorptions in the main function-oriented zones of the Yellow River Basin, a four-dimensional benchmark framework for carbon compensation zoning was constructed by total scale, economic contribution, ecological carrying capacity, and land development intensity. The SOM-K-means algorithm was used to establish a differentiated carbon compensation zoning scheme. The results showed that： ① The carbon emissions and carbon absorptions and their growth trends of the main function-oriented zones in the Yellow River Basin were in line with the positioning of the main functional area, and the significant space-time distribution characteristics of the concentration level of carbon emissions and carbon absorptions were shown. ② Significant regional differences exist in the four attributes of total carbon emissions scale, economic contribution, ecological carrying capacity, and land development intensity. The overall scale of carbon emissions showed a growth trend, with obvious comparative advantages in the midstream and downstream. The overall comparative advantage of economic contribution increased first and then decreased, with the midstream and downstream being the attribute advantage areas of economic contribution. The overall ecological carrying capacity had been improved, and the upstream had obvious advantages in ecological carrying properties. The advantageous areas for land development were mainly concentrated in the midstream and downstream； in particular, the comparative advantage index in the midstream was showing a rapid upward trend. ③ Moreover, there were 287 compensated areas, 78 balanced areas, and 185 payment areas in the Yellow River Basin. Eleven types of carbon compensation zones were finally formed by combining the comparative advantage index of four types of attributes with the plan for main function-oriented zones, and corresponding low-carbon development strategies were proposed for each type of zone.

[Spatiotemporal Evolution and Influencing Factors of Ecosystem Service Value in the Yellow River Basin].

The external spatiotemporal evolution and intrinsic impact mechanisms of ecosystem service value are of great significance for understanding regional ecosystem issues and enhancing human ecological well-being. Based on grid data, this study used the equivalent factor method and NDVI to measure the ecosystem service value of the Yellow River Basin, analyzed the spatial-temporal evolution of urban ecosystem service value along the basin, and established a GWR model to explore the spatial heterogeneity of each influencing factor on the basis of determining the main influencing factors via geographic detector. The results showed that:① The ecosystem service value of the Yellow River Basin increased first, then decreased, and finally increased from 2000 to 2020, showing a spatial distribution pattern of "the south was higher than the north;" "the lower reaches were lower, and the upper and middle reaches were higher;" and the regulation service contributed the most to the ecosystem service value of the basin. ② The results of geographical exploration showed that the degree of influence of various factors was different. Social factors played the strongest role in explaining the ecosystem service value of the Yellow River Basin, followed by economic factors, and natural factors played the weakest role. The high value areas in the upper reaches were mainly related to rivers and lakes, and the high value areas in the middle reaches were mainly related to mountains. ③ The results of the GWR model showed that population density and land reclamation rate were negatively correlated with ecosystem service value, whereas average annual precipitation was positively correlated, and the effects increased from east to west. The GDP per unit area was negatively correlated with the overall ecosystem service value but positively correlated in the upstream region.

Study on the expression changes of lncRNA in patients with systemic lupus erythematosus and its correlation with Treg cells.

OBJECTIVES: We initially explored the link between the differentially expressed long non-coding RNAs (lncRNAs) and the number of regulatory T (Treg) cells by detecting the lncRNA expression profiles in patients with systemic lupus erythematosus (SLE), then analyzed the correlation between Treg-related lncRNAs and the clinical features of SLE patients, predicting the mechanism by which lncRNAs regulate the differentiation and development of Treg cells, and provided new ideas for the treatment of SLE. METHODS: Peripheral blood of 9 active SLE patients were collected and mononuclear cells (PBMCs) were extracted; the lncRNA expression profiles of PBMCs were analyzed by whole transcriptome sequencing. Nine healthy people were used as controls to screen the differentially expressed lncRNAs, to analyze the correlation between lncRNAs and Treg cell number. Pearson test was used to analyze the correlation between lncRNAs and the number of Treg cell, and the correlation between Treg-associated lncRNA and SLEDAI score, ESR, C3, and C4 in SLE patients. The targeted genes of Treg-associated lncRNAs were predicted with miRcode and Targetscan databases and coexpression network. RESULTS: There were 240 differentially expressed lncRNAs in SLE patients compared with healthy controls, including 134 highly expressed lncRNAs (p < 0.05) and 106 lowly expressed lncRNAs (p < 0.05). The expression of ANKRD44-AS1 (r = 0.7417, p = 0.0222), LINC00200 (r = 0.6960, p = 0.0373), AP001363.2 (r = 0.7766, p = 0.0138), and LINC02824 (r = 0.7893, p = 0.0114) were positively correlated with the number of Treg cell, and the expression of AP000640.1 (r = - 0.7225, p = 0.0279), AC124248.1 (r = - 0.7653, p = 0.0163), LINC00482 (r = - 0.8317, p = 0.0054), and MIR503HG (r = - 0.7617, p < 0.05) were negatively correlated with the number of Treg cell. Among these Treg-associated lncRNAs, the expression of LINC00482 (r = - 0.7348, p < 0.05) and MIR503 HG (r = - 0.7617, p < 0.05) were negatively correlated with C3. LINC00200, ANKRD44 - AS1, and AP000640.1 related to Treg cells regulate the expression of signal transducer and activator of transcription 5 (STAT5), phospholipase D1 (PLD1), homeodomain-only protein X (HOPX), and runt-related transcription factor 3 (RUNX3) through competitive binding of miRNA or trans-regulatory mechanism, thereby regulating the differentiation and development of Treg cell. CONCLUSIONS: The lncRNA expression profiles were changed in SLE patients, the differentially expressed lncRNAs were associated with abnormal number and function of Treg cells in SLE, and Treg-associated lncRNAs were associated with SLE-disease activity, which may affect the expression of STAT5, PLD1, HOPX, RUNX3 and regulate Treg cell function and participate in the pathogenesis and progression of SLE by competitively binding to miRNAs or trans-regulatory mechanism. Key points • Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organs and systems. lncRNAs may affect Treg cells function by regulating genes expression, which may be an important pathogenesis of SLE. • This study, taking SLE as an example, preliminarily analyzed the correlation between lncRNA and Treg cells in SLE patients, analyzed the correlation between Treg-related lncRNA and the clinical characteristics of SLE, and speculated that lncRNA could regulate the differentiation and development of Treg cells through competitive combination with miRNA or trans-regulatory mechanisms. • It is possible to target epigenetic therapy for SLE.

A Convenient and Effective Preoxygenation Technique for Prolonging Deep Inspiration Breath-Hold Duration With a Venturi Mask With a 50% Oxygen Concentration.

PURPOSE: Voluntary deep inspiration breath-hold (DIBH) is commonly used in radiation therapy (RT), but the short duration of a single breath-hold, estimated to be around 20 to 40 seconds, is a limitation. This prospective study aimed to assess the feasibility and safety of using a simple preoxygenation technique with a Venturi mask to prolong voluntary DIBH. METHODS AND MATERIALS: The study included 33 healthy volunteers and 21 RT patients. Preoxygenation was performed using a Venturi mask with a 50% oxygen concentration. Paired t tests compared the duration of a single DIBH in room air and after 5, 15, and 30 minutes of preoxygenation in healthy volunteers. Sustainability of breath-hold and tolerability of heart rate and blood pressure were assessed for multiple DIBH durations in both volunteers and patients. RESULTS: In healthy volunteers, a 15-minute preoxygenation significantly prolonged the duration of a single DIBH by 24.95 seconds compared with 5-minute preoxygenation (89 ± 27.76 vs 113.95 ± 30.63 seconds; P < .001); although there was a statistically significant increase in DIBH duration after 30-minute preoxygenation, it was only extended by 4.95 seconds compared with 15-minute preoxygenation (113.95 ± 30.63 vs 118.9 ± 29.77 seconds; P < .01). After 15-minute preoxygenation, a single DIBH lasted over 100 seconds in healthy volunteers and over 80 seconds in RT patients, with no significant differences among 6 consecutive cycles of DIBH. Furthermore, there were no significant differences in heart rate or blood pressure after DIBHs, including DIBH in room air and 6 consecutive DIBHs after 15-minute preoxygenation (all P > .05). CONCLUSIONS: Preoxygenation with a 50% oxygen concentration for 15 minutes effectively prolongs the duration of 6 cycles of DIBH both in healthy volunteers and RT patients. The utilization of a Venturi mask to deliver 50% oxygen concentration provides a solution characterized by its convenience, good tolerability, and effectiveness.

Critical Role of S100A9 in Sepsis-associated Acute Kidney Injury: Mechanistic Insights through Pyroptosis Pathway Modulation.

This study investigates the role of S100A9 in sepsis-associated AKI (SA-AKI) through the lens of pyroptosis, a controlled form of cell death mediated by the gasdermin protein family. Using C57BL/6 mice and S100A9 knockout mice subjected to cecal ligation and puncture (CLP), RNA sequencing and bioinformatics analyses revealed differentially expressed genes (DEGs) related to inflammation and immune responses, with notable upregulation of S100A9. Functional enrichment analyses (GO and KEGG) indicated these DEGs are involved in interferon-beta response, immune processes, and cell adhesion. Protein-protein interaction (PPI) network analyses further emphasized S100A9's pivotal role in SA-AKI.Clinical validation measured S100A9 levels in serum and urine samples from SA-AKI patients and healthy volunteers, finding elevated S100A9 levels in the former. In vivo experiments showed that S100A9 knockout mice exhibited reduced kidney injury and inflammation, indicated by lower serum creatinine, urea nitrogen, and inflammatory markers (IL-1ß and IL-18). Histopathological analyses and immunohistochemistry confirmed less renal damage and reduced expression of cleaved IL-1ß and GSDMD-N in S100A9-deficient mice. Electron microscopy and Western blotting validated that S100A9 deficiency mitigates caspase-1-dependent pyroptosis.Cellular experiments with HK-2 cells demonstrated that S100A9 knockdown alleviated LPS-induced cell damage and reduced pyroptosis markers. These findings illuminate S100A9's involvement in NLRP3 inflammasome activation and pyroptosis, suggesting potential therapeutic targets for SA-AKI. Targeting S100A9 may offer new therapeutic avenues, improving outcomes for sepsis-related kidney injury patients. Future research should aim to validate these findings in larger clinical settings.

Throat microbiota drives alterations in pulmonary alveolar microbiota in patients with septic ARDS.

OBJECTIVES: The translocation of intestinal flora has been linked to the colonization of diverse and heavy lower respiratory flora in patients with septic ARDS, and is considered a critical prognostic factor for patients. METHODS: On the first and third days of ICU admission, BALF, throat swab, and anal swab were collected, resulting in a total of 288 samples. These samples were analyzed using 16S rRNA analysis and the traceability analysis of new generation technology. RESULTS: On the first day, among the top five microbiota species in abundance, four species were found to be identical in BALF and throat samples. Similarly, on the third day, three microbiota species were found to be identical in abundance in both BALF and throat samples. On the first day, 85.16% of microorganisms originated from the throat, 5.79% from the intestines, and 9.05% were unknown. On the third day, 83.52% of microorganisms came from the throat, 4.67% from the intestines, and 11.81% were unknown. Additionally, when regrouping the 46 patients, the results revealed a significant predominance of throat microorganisms in BALF on both the first and third day. Furthermore, as the disease progressed, the proportion of intestinal flora in BALF increased in patients with enterogenic ARDS. CONCLUSIONS: In patients with septic ARDS, the main source of lung microbiota is primarily from the throat. Furthermore, the dynamic trend of the microbiota on the first and third day is essentially consistent.It is important to note that the origin of the intestinal flora does not exclude the possibility of its origin from the throat.

[Inhibitive effect of C-21 steroidal glycosides of Cynanchum auriculatum on rat glioma cells in vitro].

OBJECTIVE: To evaluate the inhibitive effect of C-21 steroidal glycosides from the root of Cynanchum auriculatum (CGB) on rat glioma C6 cells. METHODS: C6 cells were treated with CGB for 24, 48,72 h at concentration of 30, 60, 120 mg/L, respectively. MTT assay was used for evaluating cell viability; fluorescence-activated cell sorting analysis after Annexin V/propidium iodide staining or single propidium iodide staining was used to test cell apoptosis and cell cycle. RESULTS: CGB at 30, 60, 120 mg/L concentration-dependently decreased C6 cell viability (P<0.001). CGB at 60 and 120 mg/L induced C6 cell apoptosis and cell cycle arrest. The fraction of G0/G1 cells was increased (P<0.05) and that of S phase cells was decreased (P<0.01). CONCLUSION: CGB can inhibit the growth of rat glioma C6 cells, and induce apoptosis and G0/G1 cell cycle arrest.

[Study on seed morphology of the section Cruciata Gaudin].

OBJECTIVE: To provide a scientific evidence for the identification of the section Cruciata Gaudin. METHODS: Seed morphology of the section Cruciata Gaudin in different regions from Gansu were studied by means of scanning electronic microscopy (SEM). RESULTS: The seeds of section Cruciata Gaudin had relative conformability in terms of shape,size and ornamentation. But the reticulate cell of Gentiana dahurica was obviously wider than those of other species. CONCLUSION: This study provides some useful information for classification and identification of section Cruciata Gaudin.

Polysaccharide Isolated From Tetrastigma hemsleyanum Activates TLR4 in Macrophage Cell Lines and Enhances Immune Responses in OVA-Immunized and LLC-Bearing Mouse Models.

Tetrastigma hemsleyanum Diels et Gilg is a valuable Chinese medicinal herb with a long history of clinical application. Our previous study isolated and characterized a purified polysaccharide from the aerial part of Tetrastigma hemsleyanum (SYQP) and found it having antipyretic and antitumor effects in mice. A preliminary mechanistic study suggests these effects may be related to the binding of toll-like receptor (TLR4). The objective of this study is to further explore the detailed stimulating characteristics of SYQP on TLR4 signaling pathway and its in vivo immune regulating effect. We use HEK-BLUE hTLR4, mouse and human macrophage cell lines, as research tools. In vitro results show SYQP activated HEK-BLUE hTLR4 instead of HEK-BLUE Null cells. The secretion and the mRNA expression of cytokines related to TLR4 signaling significantly increased after SYQP treatment in both PMA-induced THP-1 and RAW264.7 macrophage cell lines. The TLR4 antagonist TAK-242 can almost completely abolish this activation. Furthermore, molecules such as IRAK1, NF-κB, MAPKs, and IRF3 in both the MyD88 and TRIF branches were all activated without pathway selection. In vivo results show SYQP enhanced antigen-specific spleen lymphocyte proliferation and serum IgG levels in OVA-immunized C57BL/6 mice. Orally administered 200 mg/kg SYQP induced obvious tumor regression, spleen weight increase, and the upregulation of the mRNA expression of TLR4-related cytokines in Lewis lung carcinoma-bearing mice. These results indicate SYQP can act as both a human and mouse TLR4 agonist and enhance immune responses in mice (p < 0.05). This study provides a basis for the development and utilization of SYQP as a new type of TLR4 agonist in the future.

Acute subdural hematoma with swirl signs: clinical analysis of 15 cases.

From July 2003 to July 2009, 15 cases of subdural hematoma with swirl signs were treated in our hospital and their clinical data were retrospectively analysed. The mortality was compared between these patients and those with typical acute subdural hematoma who were treated at the same time in our hospital. Among the 15 cases, full recovery was achieved in 4 cases, slight disability in 2, grave disability in 2 and death in 7 (46.7%). The mortality of these patients was conspicuously higher than that of typical subdural hematoma (14/83, 16.9%, P < 0.01). Subdural hematoma with swirl signs is often suggestive of hazardous pathogenetic condition and early diagnosis and prompt surgical intervention is essential to reduce mortality.

MPL Adjuvant Contains Competitive Antagonists of Human TLR4.

Monophosphoryl lipid A (MPL®) is the first non-alum vaccine adjuvant to achieve widespread clinical and market acceptance, a remarkable achievement given that it is manufactured from a Salmonella enterica endotoxin. To understand how MPL® successfully balanced the dual mandate of vaccine design-low reactogenicity with high efficacy-clinical- and research-grade MPL was evaluated in human and mouse cell systems. Stimulatory dose response curves revealed that most preparations of MPL are much more active in mouse than in human cell systems, and that the limited efficacy observed in human cells correlated with TLR4 inhibitory activity that resulted in a partial agonist profile. Further analysis of the major components of MPL® adjuvant prepared synthetically identified two structural variants that functioned as competitive antagonists of human TLR4. A partial agonist profile could be recapitulated and manipulated by spiking synthetic agonists with synthetic antagonists to achieve a broad dose range over which TLR4 stimulation could be constrained below a desired threshold. This report thus identifies mixed agonist-antagonist activity as an additional mechanism by which MPL® adjuvant is detoxified, relative to its parental LPS, to render it safe for use in prophylactic vaccines.

[Reliability and validity of a Chinese version of the Quality of Life in Epilepsy Inventory (QOLIE-31-P)].

OBJECTIVE: To develop and validate a Chinese version of the Patient-Weighted Quality of Life in Epilepsy Questionnaire (QOLIE-31-P). METHODS: The original English version of the QOLIE-31-P was translated into the Chinese language. The inventory was then completed by 200 adult patients with epilepsy; and 49 patients also completed the scale twice within three weeks. Test retest, internal consistency reliabilities, construct validity, and some influential factors for quality of life in adults with epilepsy were assessed. RESULT: Test retest reliability (Pearson's correlation coefficient) for the Chinese version of the QOLIE-31-P ranged from 0.725 to 0.912 (P<0.001), and the internal consistency reliability (Cronbach's alpha coefficient) ranged from 0.627 to 0.898. Factor analysis showed that there were seven factors, which explained the total variance for 64.9%. The coefficient of seizure frequency with the quality of life was -0.81(P<0.05). The QOLIE-31-P score of the patients with tonic clonic seizure was 55.7 +/-16.6, and that of other seizure type was 61.4 +/-18.7(t=-2.568, P<0.05). CONCLUSION: The psychometric properties of the Chinese version of the QOLIE-31-P have satisfactory reliability and validity, and can be applied to assess quality of life in Chinese adult patients with epilepsy.

Polysaccharide from Phellinus Igniarius activates TLR4-mediated signaling pathways in macrophages and shows immune adjuvant activity in mice.

Polysaccharide from Phellinus igniarius (PPI) is known for its immune-regulating effect with low toxicity. Toll like receptor 4 (TLR4) is important in both innate and adaptive immune responses and considered to be a promising target for new immune adjuvants. In this study, PPI was investigated for its effect on activating TLR4 in RAW264.7 and peritoneal macrophages. The adjuvant potential of PPI was evaluated in OVA-immunized mice. The results showed PPI treatment significantly increased the secretion and the mRNA expression of both MyD88 dependent and TRIF dependent cytokines. IRAK-1, a key molecule on the downstream of MyD88, was polyubiquitinated while IRF-3, another key molecule on the downstream of TRIF, was phosphorylated obviously after the treatment of PPI. The phosphorylation of molecules involved in both NF-κB pathway and MAPK pathway were significantly up-regulated after PPI treatment. In addition, the effects of PPI on the macrophages almost completely disappeared after treating the cells with the TLR4 antagonist TAK-242. Further in vivo results showed PPI significantly increased the serum OVA-specific antibody and the OVA-specific spleen cell proliferation. Taken together, PPI can specifically stimulate TLR4 and activate both MyD88 and TRIF pathways. PPI has immune adjuvant activity and may become a new potential immune adjuvant.