Association between Parkinson's disease and cardiovascular disease mortality: a prospective population-based study from NHANES.

BACKGROUND AND AIM: Conflicting results have been reported on the association between Parkinson's disease (PD) and cardiovascular disease (CVD) mortality in different populations. Therefore, studying the relationship between PD and CVD mortality is crucial to reduce mortality caused by the former. METHODS: In this cohort investigation, we enrolled 28,242 participants from the National Health and Nutrition Examination Survey spanning from 2003 to 2018. The 380 cases of PD in the cohort were identified by documenting 'ANTIPARKINSON AGENTS' in their reported prescription medications. Mortality outcomes were ascertained by cross-referencing the cohort database with the National Death Index, which was last updated on 31 December 2019. Cardiovascular disease mortality was categorised according to the 10th revision of the International Classification of Diseases by using a spectrum of diagnostic codes. Weighted multivariable Cox regression analysis was used to examine the association between PD and the risk of CVD mortality. RESULTS: A total of 28,242 adults were included in the study [mean age, 60.156 (12.55) years, 13,766 men (48.74%)], and the median follow-up period was 89 months. Individuals with PD had an adjusted HR of 1.82 (95% CI, 1.24-2.69; p = 0.002) for CVD mortality and 1.84 (95% CI, 1.44-2.33; p < 0.001) for all-cause mortality compared with those without PD. The association between PD and CVD mortality was robust in sensitivity analyses, after excluding participants who died within 2 years of follow-up and those with a history of cancer at baseline [HR,1.82 (95% CI, 1.20-2.75; p = 0.005)]. CONCLUSIONS: PD was associated with a high long-term CVD mortality rate in the US population.

Enriched rhizospheric functional microbiome may enhance adaptability of Artemisia lavandulaefolia and Betula luminifera in antimony mining areas.

Dominant native plants are crucial for vegetation reconstruction and ecological restoration of mining areas, though their adaptation mechanisms in stressful environments are unclear. This study focuses on the interactions between dominant indigenous species in antimony (Sb) mining area, Artemisia lavandulaefolia and Betula luminifera, and the microbes in their rhizosphere. The rhizosphere microbial diversity and potential functions of both plants were analyzed through the utilization of 16S, ITS sequencing, and metabarcoding analysis. The results revealed that soil environmental factors, rather than plant species, had a more significant impact on the composition of the rhizosphere microbial community. Soil pH and moisture significantly affected microbial biomarkers and keystone species. Actinobacteria, Proteobacteria and Acidobacteriota, exhibited high resistance to Sb and As, and played a crucial role in the cycling of carbon, nitrogen (N), phosphorus (P), and sulfur (S). The genes participating in N, P, and S cycling exhibited metabolic coupling with those genes associated with Sb and As resistance, which might have enhanced the rhizosphere microbes' capacity to endure environmental stressors. The enrichment of these rhizosphere functional microbes is the combined result of dispersal limitations and deterministic assembly processes. Notably, the genes related to quorum sensing, the type III secretion system, and chemotaxis systems were significantly enriched in the rhizosphere of plants, especially in B. luminifera, in the mining area. The phylogenetic tree derived from the evolutionary relationships among rhizosphere microbial and chloroplast whole-genome resequencing results, infers both species especially B. luminifera, may have undergone co-evolution with rhizosphere microorganisms in mining areas. These findings offer valuable insights into the dominant native rhizosphere microorganisms that facilitate plant adaptation to environmental stress in mining areas, thereby shedding light on potential strategies for ecological restoration in such environments.

Divergent responses of rhizosphere soil phosphorus fractions and biological features of Salix psammophila to fertilization strategies under cadmium contamination.

Soil oligotrophy in areas heavily contaminated with heavy metals poses a significant challenge to vegetation establishment and phytoremediation processes. Phosphorus (P) cycling plays a critical role in global biogeochemical cycles, but there is limited understanding of its response to varying fertilization strategies and its correlation with phytoremediation effectiveness. This study primarily investigated the effects of various fertilization strategies, including nitrogen (N, 300 mg·kg-1), P (100 mg·kg-1), NP (combined N and P at 300 mg·kg-1 and 100 mg·kg-1, respectively), and HP (high P, 300 mg·kg-1) application, on rhizosphere soil P fractions and P-solubilizing microbial community (harboring phoD and phoC genes, respectively) of Salix psammophila under cadmium contamination. Application of NP significantly enhanced plant growth and cadmium accumulation, whereas HP inhibited cadmium bioaccumulation but promoted its translocation. Compared to untreated soil, N application promoted P cycling, leading to increases of 141.9 %, 60.4 %, and 10.3 % in Resin-Pi, diluted HCl-Pi, and conc.HCl-Pi, respectively. P application decreased organic phosphorus (Po) fractions by 24.4 % - 225.8 %, but N incorporation mitigated the declining trend in Po and augmented alkaline phosphatase activity. Fertilization strategies significantly regulated phoC- or phoD-harboring bacterial community structure, but their differential nutrient demands resulted in distinct responses. The phoD-harboring bacteria exhibited higher diversity and network complexity, with numerous biomarkers and fertilizer-sensitive OTUs discovered across treatments. Structural equation modeling (SEM) analysis indicated that phytoremediation efficiency was directly affected by Pi fractions, and phoD-harboring bacteria exhibited stronger associations with Pi fractions than phoC-harboring bacteria. In conclusion, our results reveal potential pathways through which fertilization strategies influence phytoremediation by affecting the structure of P-solubilizing microbial community. Furthermore, our study emphasizes the importance of combined N and P application in promoting Cd accumulation in plants, with high P levels appearing as an ideal fertilization strategy for phytoremediation targeting the harvest of aboveground biomass.

Predictive value of hyponatremia for short-term mortality in supratentorial spontaneous intracerebral hemorrhage: a single center study.

Background: Hyponatremia is a common electrolyte disturbance in patients with neurological disease; however, its predictive role for outcome in patients with supratentorial spontaneous intracerebral hemorrhage (sICH) is controversial. This study aims to explore the association between hyponatremia within 7 days after bleeding and 90-day mortality in patients with supratentorial sICH. Methods: A retrospective analysis was conducted at our institution. Patients with sICH meeting the inclusion criteria were enrolled in this study. Multivariate regression analyses were performed to determine the predictive value of hyponatremia (serum sodium <135 mmol/L) for 90-day mortality and functional outcome. Subgroup analysis was performed based on the degree and duration of hyponatremia and therapeutic strategies. The Spearman correlation test was performed to explore the relationship between hyponatremia severity and duration with variables in a multivariate regression model. Kaplan-Meier curve was depicted to reveal the relationship between hyponatremia and mortality. The receiver operating characteristic (ROC) curve was plotted to show the diagnostic effect of the minimum concentration of serum sodium (sodiummin) on 90-day mortality. Results: A total of 960 patients were enrolled, 19.6% (188) of whom were patients with hyponatremia and 26.0% (250) had 90-day mortality. The incidence of hyponatremia was roughly 2.5 times in non-survivors compared with survivors (34.8% vs. 14.2%). Multivariate regression analysis revealed that hyponatremia was the independent predictor of 90-day mortality (OR 2.763, 95%CI 1.836-4.157) and adverse outcome (OR 3.579, 95%CI 2.332-6.780). Subgroup analysis indicated an increased trend in mortality risk with both duration (more or less than 48 h) and severity of hyponatremia (mild, moderate, and severe) and confirmed the predictive value of hyponatremia for mortality in patients undergoing surgical intervention (external ventricular drainage, craniotomy, and decompressive craniectomy; all p < 0.05). The Spearman correlation test indicated no moderate or strong relationship between hyponatremia severity and duration with other variables in the multivariate model (all |rs| < 0.4). The ROC curve suggested the moderate diagnostic performance of sodiummin for mortality in both general patients and subgroups of therapeutic method patients (AUC from 0.6475 to 0.7384). Conclusion: Hyponatremia occurring in the first 7 days after bleeding is an independent predictor of 90-day morality and adverse outcome. Rigorous electrolyte scrutiny in patients treated surgically is required.

Modulating phyllosphere microbiome structure and function in Loropetalum chinense and Osmanthus fragrans: The impact of foliar dust and heavy metals.

Trees can effectively capture airborne particles and improve air quality. However, the specific response of phyllosphere microbiome (PMo) in different plant species to particulate matter (PM) and the heavy metals it contains are not yet fully understood. In this study, we investigated the impact of PM on the diversity and function of PMo in Loropetalum chinense and Osmanthus fragrans trees grown in industrial and clean zones with varying levels of PM pollution. Our findings revealed that leaf dust had a significant negative effect on microbial richness, with O. fragrans exhibiting higher microbial diversity than L. chinense. The dominant phylum of phyllosphere bacteria in all samples was Proteobacteria, and the dominant genera were Stenotrophomonas and Delftia. The relative abundance of these genera varied significantly among plant species and regions. Our results showed that PM had a significant impact on the community composition of PMo, with the presence of heavy metals exerting a greater effect than particle size. Moreover, the foliar microbial community of plants grown in industrial zones exhibited significantly higher metabolic functions related to stress resistance and disease resistance compared to plants in control zones. These findings highlight the structural and functional responses of PMo to PM and indicate their potential for enhancing plant adaptation to environmental stress.

Safety and Efficacy of Hybrid Surgery in Chronic Internal Carotid Artery Occlusion: A Systematic Review and Meta-Analysis.

INTRODUCTION: Chronic internal carotid artery occlusion (CICAO) is a common cause of stroke and ischemia recurrence. An increasing number of reports have highlighted the potential of hybrid surgery for treating CICAO. There are few studies, specifically nonrandomized controlled trials, on the safety and effectiveness of hybrid surgery for the treatment of CICAO, so in this study, we hypothesized that hybrid surgery would be safe, have an acceptable complication rate and a high success rate. METHODS: MEDLINE, Embase, Cochrane Library, and Web of Science databases were searched for relevant studies published up to January 30, 2023. The primary endpoint was recanalization rates of occluded vessels, and the secondary endpoint was perioperative death and procedure-related complications. Subgroup analysis focused on the recanalization rates of endovascular intervention (EI) and hybrid surgery, as well as the rates of recanalization below the clinoid segment and at the clinoid segment and beyond. The follow-up visit was conducted at least 3 months after surgery, and stenosis or occlusion recurrence was confirmed by review of CTA or DSA scan. RESULTS: The databases were searched and 1,709 records were identified, of which 16 articles were used in the meta-analysis, and 464 CICAO patients with complete data who underwent hybrid surgery were enrolled. Hybrid surgery was associated with higher success rates (RD = 0.87, 95% CI [0.84-0.91], p < 0.00001) than EI (OR = 4.71, 95% CI [2.32-9.56], p < 0.0001). The procedural success rate in the below-clinoid segment group was significantly higher than that in the clinoid segment and beyond group (OR = 13.76, 95% CI [5.31-35.66], p < 0.00001). The total periprocedural complication rate was low (RD = 0.11, 95% CI [0.07-0.15], p < 0.00001 and RD = 0.04, 95% CI [0.00-0.07], p = 0.03). Target vessel restenosis or reocclusion occurred in 35 patients (8%) during the follow-up period (RD = 0.08, 95% CI [0.04-0.12], p < 0.0001). CONCLUSION: Hybrid surgery is the combination of the advantages of open surgery and EI, has a high success rate and a low risk of recurrence of stenosis and occlusion in the long term. Randomized controlled trials on hybrid surgery for internal carotid artery occlusion are necessary.

Evaluating the role of rhizosphere microbial home-field advantage in Betula luminifera adaptation to antimony mining areas.

It has been established that the coevolution of plants and the rhizosphere microbiome in response to abiotic stress can result in the recruitment of specific functional microbiomes. However, the potential of inoculated rhizosphere microbiomes to enhance plant fitness and the inheritance of adaptive traits in subsequent generations remains unclear. In this study, cross-inoculation trials were conducted using seeds, rhizosphere microbiome, and in situ soil collected from areas of Betula luminifera grown in both antimony mining and control sites. Compared to the control site, plants originating from mining areas exhibited stronger adaptive traits, specifically manifested as significant increases in hundred-seed weight, specific surface area, and germination rate, as well as markedly enhanced seedling survival rate and biomass. Inoculation with mining microbiomes could enhance the fitness of plants in mining sites through a "home-field advantage" while also improving the fitness of plants originating from control sites. During the initial phase of seedling development, bacteria play a crucial role in promoting growth, primarily due to their mechanisms of metal resistance and nutrient cycling. This study provided evidence that the outcomes of long-term coevolution between plants and the rhizosphere microbiome in mining areas can be passed on to future generations. Moreover, it has been demonstrated that transgenerational inheritance and rhizosphere microbiome inoculation are important factors in improving the adaptability of plants in mining areas. The findings have important implications for vegetation restoration and ecological environment improvement in mining areas.

Microbial communities in tree root-compartment niches under Cd and Zn pollution: Structure, assembly process and co-occurrence relationship.

Woody plants have showed great potential in remediating severely contaminated soils by heavy metals (HMs) due to their cost-efficient and ecologically friendly trait. It is believed the root-associated microbiota plays a vital role in phytoremediation for HMs. However, the ecological process controlling the assembly and composition of tree root-associated microbial communities under HMs stress remains poorly understood. Herein, we profiled the bulk soil, rhizosphere and endosphere microbial communities of trees growing in heavily Cd and Zn polluted soil. The microbiota was gradually filtered from bulk soil to the tree roots and was selectively enriched in roots with specific taxa, such as Proteobacteria and Ascomycota. The microbial community assembly along the soil-root continuum was mainly controlled by deterministic processes from bulk soil to the endosphere, with the normalized stochasticity ratio (NST) indices of 67.16-31.05 % and 30.37-15.02 % for bacteria and fungi, respectively. Plant selection pressure sequentially increased from bulk soil to rhizosphere to endosphere, with the reduced bacterial alpha diversity accompanying the consequently reduced complexity of the co-occurrence network. Together, the findings provide new evidence for horizontal transmission of endophytic microbiome from soil to the host, which can shed light on the future screening and application of microbial-assisted phytoremediation.

Current understanding of macrophages in intracranial aneurysm: relevant etiological manifestations, signaling modulation and therapeutic strategies.

Macrophages activation and inflammatory response play crucial roles in intracranial aneurysm (IA) formation and progression. The outcome of ruptured IA is considerably poor, and the mechanisms that trigger IA progression and rupture remain to be clarified, thereby developing effective therapy to prevent subarachnoid hemorrhage (SAH) become difficult. Recently, climbing evidences have been expanding our understanding of the macrophages relevant IA pathogenesis, such as immune cells population, inflammatory activation, intra-/inter-cellular signaling transductions and drug administration responses. Crosstalk between macrophages disorder, inflammation and cellular signaling transduction aggravates the devastating consequences of IA. Illustrating the pros and cons mechanisms of macrophages in IA progression are expected to achieve more efficient treatment interventions. In this review, we summarized the current advanced knowledge of macrophages activation, infiltration, polarization and inflammatory responses in IA occurrence and development, as well as the most relevant NF-κB, signal transducer and activator of transcription 1 (STAT1) and Toll-Like Receptor 4 (TLR4) regulatory signaling modulation. The understanding of macrophages regulatory mechanisms is important for IA patients' clinical outcomes. Gaining insight into the macrophages regulation potentially contributes to more precise IA interventions and will also greatly facilitate the development of novel medical therapy.

Inflammation and immune cell abnormalities in intracranial aneurysm subarachnoid hemorrhage (SAH): Relevant signaling pathways and therapeutic strategies.

Intracranial aneurysm subarachnoid hemorrhage (SAH) is a cerebrovascular disorder associated with high overall mortality. Currently, the underlying mechanisms of pathological reaction after aneurysm rupture are still unclear, especially in the immune microenvironment, inflammation, and relevant signaling pathways. SAH-induced immune cell population alteration, immune inflammatory signaling pathway activation, and active substance generation are associated with pro-inflammatory cytokines, immunosuppression, and brain injury. Crosstalk between immune disorders and hyperactivation of inflammatory signals aggravated the devastating consequences of brain injury and cerebral vasospasm and increased the risk of infection. In this review, we discussed the role of inflammation and immune cell responses in the occurrence and development of aneurysm SAH, as well as the most relevant immune inflammatory signaling pathways [PI3K/Akt, extracellular signal-regulated kinase (ERK), hypoxia-inducible factor-1α (HIF-1α), STAT, SIRT, mammalian target of rapamycin (mTOR), NLRP3, TLR4/nuclear factor-κB (NF-κB), and Keap1/nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/ARE cascades] and biomarkers in aneurysm SAH. In addition, we also summarized potential therapeutic drugs targeting the aneurysm SAH immune inflammatory responses, such as nimodipine, dexmedetomidine (DEX), fingolimod, and genomic variation-related aneurysm prophylactic agent sunitinib. The intervention of immune inflammatory responses and immune microenvironment significantly reduces the secondary brain injury, thereby improving the prognosis of patients admitted to SAH. Future studies should focus on exploring potential immune inflammatory mechanisms and developing additional therapeutic strategies for precise aneurysm SAH immune inflammatory regulation and genomic variants associated with aneurysm formation.

Effects of copper oxide nanoparticles on Salix growth, soil enzyme activity and microbial community composition in a wetland mesocosm.

A model wetland with Salix was established to investigate the effects of CuO nanoparticles (NPs; the equivalent amount of Cu at 0, 100 and 500 mg/kg) on plant, soil enzyme activity and microbial community. Ionic Cu (100, 500 mg/kg) and bulk-sized CuO particles (BPs, 500 mg/kg) were included as controls. The results suggested the CuO NPs at 500 mg/kg and ionic Cu treatments inhibited the plant growth, while CuO NPs at 100 mg/kg and CuO BPs at 500 mg/kg played a facilitating role. CuO NPs significantly decreased the activities of peroxidase and polyphenol oxidase, while ionic Cu treatments increased peroxidase activity, BPs and ionic Cu (500 mg/kg) increased the polyphenol oxidase activity. Bacterial community richness and diversity were reduced in all Cu treatments; however, CuO NPs and BPs at 500 mg/kg significantly increased the richness and diversity of fungal community.Soil microbial community was significantly altered by Cu types and dose. In comparison with ionic Cu and CuO BPs, CuO NPs uniquely enriched the microbial community and the fungal families.Overall, it demonstrate that both particle size and dose regulate the impact of CuO on wetland ecology, which deepens our understanding on the ecological risks of CuO NPs in freshwater forested wetland.

Identification of UGP2 as a progression marker that promotes cell growth and motility in human glioma.

Glioblastoma (GBM) is one of the most common highly malignant primary brain tumor with poor prognosis. This study aimed to explore the possible mechanism by bioinformatics method and detect potential function of UGP2 of GBM. Gene expression microarray data of GSE4412 and messenger RNA-sequencing data of GBM with samples clinical information were downloaded from the Gene Expression Omnibus database and The Cancer Genome Atlas database, respectively. Differentially expressed genes (DEGs) analysis using the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology based on R language. A total of 1000 common DEGs were identified in GBM samples, including 353 upregulated and 647 downregulated genes. Based on the random survival forest model, we identified UDP-glucose pyrophosphorylase 2 (UGP2) (upregulated gene) had a significant effect on GBM prognosis. Functional enrichment showed that UGP2 was enriched in the biological progresses of cell proliferation, migration, and invasion. Furthermore, UGP2 expression is aberrantly overexpressed in human glioma and positively correlated with pathologic grade. A loss-of-function study showed that knockdown of UGP2 decreases U251 cell growth, migration, and invasion in vivo and vitro. We proposed the development and progression of human glioma were associated with survival based on bioinformatics analysis. We also found that UGP2 might function as prognostic markers in the pathogenesis of GBM.

A novel serum microRNA-based identification and classification biomarker of human glioma.

Malignant glioma is one of the most common primary brain tumors that develop via multiple pathways and gene deregulation. MicroRNAs are involved in human cancer development and progression, and their serum expression profiles of glioma patients may be useful for classifying cancers. However, the profile and molecular mechanism of serum microRNAs for human glioma are poorly understood. Thus, it is crucial to analyze microRNA expression in human glioma serum to identify molecular subclasses and early stage of glioma. In this study, we performed microRNA alteration that contributes to glioma profile via analysis of The Cancer Genome Atlas RNA sequencing data and other independent Gene Expression Omnibus microarray data. We identified the glioma-associated novel microRNA as a key regulator of human glioma development and progression. The putative novel miR-1825 was validated by real-time polymerase chain reaction and its expression was significantly decreased in the serum of glioma patients compared with healthy controls. Patients with high miR-1825 expression had a longer survival rate. Interestingly, we found that miR-1825 expression levels were dependent on tumor size and pathological grading in glioma patients, but not associated with other factors including age and T classification. MicroRNA-Gene Ontology network indicated that miR-1825 may play an important role in the development of human glioma including apoptosis, cell proliferation, and invasion. In vitro assays of miR-1825 inhibit U87 cell proliferation and invasion and induce apoptosis. Furthermore, we provide evidence that the tumor-suppressive microRNA miR-1825 controls KLF2 expression. Reporter gene analyses revealed that both microRNAs directly targeted the 3'-untranslated region of KLF2 messenger RNA. These data demonstrated that miR-1825 expression in serum of human glioma was associated with tumorigenesis and miR-1825 may be used as a biomarker for identification of the pathological grade of glioma.

Role of hepcidin and its downstream proteins in early brain injury after experimental subarachnoid hemorrhage in rats.

Early brain injury (EBI) is a major cause of mortality from subarachnoid hemorrhage (SAH). We aimed to study the pathophysiology of EBI and explore the role of hepcidin, a protein involved in iron homeostatic regulation, and its downstream proteins. One hundred and thirty-two male Sprague-Dawley rats were assigned into groups (n = 24/group): sham, SAH, SAH + hepcidin, SAH + hepcidin-targeting small interfering ribonucleic acid (siRNA), and SAH + scramble siRNA. Three hepcidin-targeting siRNAs and one scramble siRNA for hepcidin were injected 24 h before hemorrhage induction, and hepcidin protein was injected 30 min before induction. The rats were neurologically evaluated at 24 h and euthanized at 72 h. Hepcidin, ferroportin-1, and ceruloplasmin protein expression were measured by immunohistochemistry and Western blotting. Brain water content, blood-brain barrier (BBB) leakage, non-heme tissue iron and Garcia scale were evaluated. Hepcidin expression increased in the cerebral cortex and hippocampus after experimental SAH (P < 0.05 compared to sham), while ferroportin-1 and ceruloplasmin decreased (P < 0.05). Hepcidin injection lowered the expression of ferroportin-1 and ceruloplasmin further but siRNA reduced the levels of hepcidin (P < 0.05 compared to SAH) resulting in recovery of ferroportin-1 and ceruloplasmin levels. Apoptosis was increased in SAH rats compared to sham (P < 0.05) and increased slightly more by hepcidin, but decreased by siRNA (P < 0.05 compared to SAH). SAH rats had lower neurological scores, high brain water content, BBB permeability, and non-heme tissue iron (P < 0.05). In conclusion, downregulation of ferroportin-1 and ceruloplasmin caused by hepcidin enhanced iron-dependent oxidative damage and may be the potential mechanism of SAH.

An integrated transcriptomic and computational analysis for biomarker identification in human glioma.

Malignant glioma is one of the most common primary brain tumors and is among the deadliest of human cancers. The molecular mechanism for human glioma is poorly understood. Early prognosis of this disease and early treatment are vital. Thus, it is crucial to target the key genes controlling pathogenesis in the early stage of glioma. In this study, differentially expressed genes in human glioma and paired peritumoral tissues were detected by transcriptome microarray analysis. Following gene microarray analysis, the gene expression profile in the differential grade glioma was further validated by bioinformatic analyses, co-expression network construction. Microarray analysis revealed that 1725 genes were differentially expressed and classified into different glioma stage. The analysis revealed 14 genes that were significantly associated with survival with a false discovery rate. Among these genes, macrophage capping protein (CAPG), a member of the actin-regulatory protein, was the key gene in a 20-gene network that modulates cell motility by interacting with the cytoskeleton. Furthermore, the prognostic impact of CAPG was validated by use of quantitative real-time polymerase chain reaction (qPCR) and immunohistochemistry on human glioma tissue. CAPG protein was significantly upregulated in clinical high-grade glioblastoma as compared with normal brain tissues. Overexpression of CAPG levels also predict shorter overall survival of glioma patients. These data demonstrated CAPG protein expression in human glioma was associated with tumorigenesis and may be a biomarker for identification of the pathological grade of glioma.

[Enhanced expression of Toll-like receptor 3 in the basilar arteries and hippocampus of subarachnoid hemorrhage rats].

OBJECTIVE: To observe the dynamic expression and significance of Toll-like receptor 3 (TLR3) in subarachnoid hemorrhage (SAH) model. METHODS: SAH model was established using blood injection into the prechiasmatic cistern. Sixty SD rats were randomly divided into sham group and SAH groups (including SAH 1-, 3-, 7-day groups), each with 15 rats. The operation steps were the same in groups except the sham group that was injected with normal saline instead. At different time points after modeling, the basilar arteries and brain were obtained. The mRNA and protein expression of TLR3 was detected using reverse transcription PCR, Western blotting and immunohistochemistry, respectively. Meanwhile, the distribution of TLR3 was analyzed using the immunofluorescence double labeling technique. RESULTS: The mRNA and protein expression of TLR3 was weak in sham group and highly expressed in SAH groups, and the highest expression were found in SAH 3-day group. Immunohistochemistry showed that TLR3 was highly expressed in vascular endothelial and hippocampal neurons. The sham group showed a weak TLR3 expression in the cytoplasm, while the SHA group showed the strongly expressed TLR3 mainly in the nucleus and cytoplasm. The result of immunofluorescence double labeling also suggested TLR3 was co-localization with CD34 in the endothelial cells. CONCLUSION: The TLR3 expression was enhanced in the basilar arteries and hippocampus when the rats suffered from SAH, which suggested TLR3 might play a certain role in the pathogenesis of SAH.

Optimal hemoglobin concentration in patients with aneurysmal subarachnoid hemorrhage after surgical treatment to prevent symptomatic cerebral vasospasm.

Medical complications occur frequently after aneurismal subarachnoid hemorrhage (aSAH), such as cerebral vasospasm (CVS), anemia, etc. The relationship between hemoglobin (Hgb) concentration and the occurrence of CVS after aSAH remains largely elusive. A total of 218 patients with postoperative aSAH were recruited. Symptomatic cerebral vasospasm (SCVS) was initially diagnosed on the basis of their clinical signs and symptoms, and confirmed by imaging tests. The patients were then divided into four groups on the basis of the postoperative mean Hgb concentration (<11, 11-12, 12-13, and >13 g/dl). The possible influential factors that were statistically significant in the initial univariate analysis were subjected to a multivariable logistic regression analysis. Univariate analysis showed that Hunt and Hess neurological grade on admission, intraoperative aneurysm rupture, CT Fisher grade, and postoperative mean Hgb were associated significantly with SCVS in aSAH patients after surgical treatment (P<0.05). Subsequent multivariable analysis showed that postoperative mean Hgb remained significant after adjustment for Hunt and Hess neurological grade on admission and CT fisher grade. The incidence of SCVS in the group with an Hgb concentration 11-12 g/dl was found to be the lowest among all groups [odds ratio (OR), 3.29, 95% confidence interval (CI), 1.43-7.58, P=0.005; OR, 3.63, 95% CI, 1.41-9.34, P=0.007; OR, 5.34, 95% CI, 1.85-15.43, P=0.002]. Postoperative Hgb concentration is an independent risk factor for SCVS in aSAH patients following surgery, and maintaining the concentration at 11-12 g/dl may reduce the incidence of SCVS.

Virological responses in chronic hepatitis C patients undergoing prolonged therapy with low-dose Peg-IFNα-2a.

BACKGROUND/AIMS: Standard dose therapy with pegylated interferon α-2a (Peg-IFNα-2a) and ribavirin is not suitable for all patients because of the side effects. This study aims to evaluate the virological responses of low-dose but long-course Peg-IFNα-2a therapy compared with standard therapy. METHODOLOGY: Ninety patients with chronic hepatitis C were divided into three groups according to their tolerance to Peg-IFNα-2a. The courses of treatment were 96 or 48 weeks respectively in patients with HCV genotypes 1b or 2a in the 67.5 µg and 90 µg groups, and were 48 or 24 weeks in the 180 µg groups. Serum HCV RNA was quantified to determine RVR, EVR, SVR and ETR. RESULTS: There were no statistical differences in HCV RNA load, HCV genotype at the baseline of the three groups (p>0.05). The rates of RVR, EVR, SVR and ETR (no significant differences in each group), were 63.04%, 82.61%, 71.74% and 85.87% in all 92 patients. Genotype 1b (95% CI=11.97-82.89; p=0.0075) and RVR (95% CI=0.12-0.53; p<0.001) were important predictors of SVR. CONCLUSIONS: Patients with low-dose but long-course Peg-IFNα-2a therapy had similar virological responses compared to those with standard therapy. HCV genotype and RVR were independent predictors of SVR.

[The virological response in prolonged therapy of chronic hepatitis C with low-dose peginterferon alpha-2a].

OBJECTIVE: To investigate the virological response in prolonged therapy of chronic hepatitis C (CHC) with low-dose peginterferon alpha-2a. METHODS: The 92 cases of in-patients with chronic hepatitis C in September 2004 to September 2006 were divided to three groups according the endurance of interferon. The dose of peginterferon alpha-2a was 67.5 microg, 90 microg and 180 microg per week in group A, B and C respectively. The treatment duration of peginterferon alpha-2a was 96 or 48 weeks in HCV genotype 1b and 2a in group A and B, and in the group C the duration was 48 or 24 weeks in genotype 1b and 2a patients respectively. Meanwhile, ribavirin for 900-1200 mg per day combined treated with all patients. The quantitation of serum HCV RNA were conducted to determine the rapid virological response (RVR), early virological response (EVR) and sustained virological response (SVR) respectively. RESULTS: There were no significant difference between the three groups in the rate of RVR, EVR and SVR (P > 0.05). There was a higer rate of RVR, EVR and SVR in the genotype 2a group than the genotype 1b group (P < 0.05). HCV genotype was the independent predictor (OR = 12.78, 95%, CI = 11.97-82.89, P = 0.0075) of SVR. CONCLUSION: There was a similar virological response between prolonged therapy of chronic hepatitis C with low-dose peginterferon alpha-2a and the standard dose and duration. The genotype was the independent predictors of SVR in peginterferon alpha-2a antiviral therapy of chronic hepatitis C.