Eucommia Polysaccharides Ameliorate Aging-Associated Gut Dysbiosis: A Potential Mechanism for Life Extension in Drosophila.

The gut microbiota is increasingly considered to play a key role in human immunity and health. The aging process alters the microbiota composition, which is associated with inflammation, reactive oxygen species (ROS), decreased tissue function, and increased susceptibility to age-related diseases. It has been demonstrated that plant polysaccharides have beneficial effects on the gut microbiota, particularly in reducing pathogenic bacteria abundance and increasing beneficial bacteria populations. However, there is limited evidence of the effect of plant polysaccharides on age-related gut microbiota dysbiosis and ROS accumulation during the aging process. To explore the effect of Eucommiae polysaccharides (EPs) on age-related gut microbiota dysbiosis and ROS accumulation during the aging process of Drosophila, a series of behavioral and life span assays of Drosophila with the same genetic background in standard medium and a medium supplemented with EPs were performed. Next, the gut microbiota composition and protein composition of Drosophila in standard medium and the medium supplemented with EPs were detected using 16S rRNA gene sequencing analysis and quantitative proteomic analysis. Here, we show that supplementation of Eucommiae polysaccharides (EPs) during development leads to the life span extension of Drosophila. Furthermore, EPs decreased age-related ROS accumulation and suppressed Gluconobacter, Providencia, and Enterobacteriaceae in aged Drosophila. Increased Gluconobacter, Providencia, and Enterobacteriaceae in the indigenous microbiota might induce age-related gut dysfunction in Drosophila and shortens their life span. Our study demonstrates that EPs can be used as prebiotic agents to prevent aging-associated gut dysbiosis and reactive oxidative stress.

MRI features of neuronal intranuclear inclusion disease, combining visual and quantitative imaging investigations.

OBJECTIVE: To observe the radiological characteristics of Neuronal Intranuclear Inclusion Disease (NIID) on lesion locations and diffusion property using quantitative imaging analysis. METHODS: Visual inspection and quantitative analyses were performed on MRI data from 31 retrospectively included patients with NIID. Frequency heatmaps of lesion locations on T2WI and DWI were generated using voxel-wise analysis. Gray matter volume (GMV), white matter volume (WMV) and diffusion property of apparent diffusion coefficient (ADC) values of patients were voxel-wisely compared with healthy controls. Moreover, the ADC values within the DWI-detected lesion were compared with those within the adjacent cortical gray matter and white matter. Voxel-based lesion symptom mapping (VLSM) techniques, were used to determine the relationship between DWI lesion location and disease durations. RESULTS: By visual inspection on the imaging findings, we proposed an "cockscomb flower sign" for describing the radiological feature of DWI hyperintensity within the corticomedullary junction. A "T2WI-DWI mismatch of spatial distribution" pattern was also revealed with visual inspection and frequency heatmaps, for describing the feature of a wider lesion distribution covering white matter shown on T2WI than that on DWI. Voxel-based morphometry comparison revealed that wildly reduced GMV and WMV, both the lesion areas detected by DWI and T2WI demonstrated ADC increase in patients. Furthermore, the ADC values within the DWI-detected lesion were intermediate between the adjacent cortex and the deep white matter with highest ADC. VLSM analysis revealed that frontal lobe, parietal lobe and internal capsule damage were associated with higher NIID durations. CONCLUSION: NIID features with "cockscomb flower-like" DWI hyperintensity in area of corticomedullary junction, based on a "T2WI-DWI mismatch of spatial distribution" of lesion locations. The pathological substrate of corticomedullary junction hyperintensity on DWI, can not be explained as diffusion restriction. These typical radiological features of brain MRI would be helpful for diagnosis of NIID.

[PKEP with complete preservation of the urethral mucosa in the 11－1 o'clock position improves urinary continence and protects erectile function in BPH patients].

OBJECTIVE: To evaluate the effect of transurethral plasmakinetic enucleation of the prostate (PKEP) with complete preservation of the urethral mucosa in the 11－1 o'clock position on urinary continence and erectile function in BPH patients. METHODS: We retrospectively analyzed the clinical data on 84 cases of BPH treated by traditional PKEP (group A, n = 48) or modified PKEP with complete preservation of the urethral mucosa in the 11－1 o'clock position (group B, n = 36) from January 2017 to December 2021. All the patients had sexual activities within three months preoperatively. We followed up the patients for 12 months after surgery and compared the baseline, surgery-related and follow-up data between the two groups of patients. RESULTS: There were no statistically significant differences between the two groups of patients in age, disease duration, prostate volume, preoperative postvoid residual urine (PVR), preoperative maximum urinary flow rate (Qmax), IPSS, PSA level, QOL scores or IIEF-5 scores, nor in the operation time, intraoperative hemoglobin decrease, volume of resected tissue, bladder flushing time, postoperative hospital stay, or postoperative improvement of Qmax and IPSS. The rate of urinary continence was significantly higher in group B than in A at 1 month postoperatively (66.67% ï¼»24/36ï¼½ vs 43.25% ï¼»20/48ï¼½, P = 0.025) and so were IIEF-5 scores at 6 months (16.69 ± 3.21 vs 15.27 ± 2.74, P = 0.032) and 12 months (18.04 ± 2.04 vs 16.96 ± 2.54, P = 0.039), while the incidence rate of retrograde ejaculation markedly lower in the former than in the latter group at 6 months (33.33% ï¼»12/36ï¼½ vs 56.25% ï¼»28/48ï¼½, P = 0.018) and 12 months (25% ï¼»9/36ï¼½ vs 47.92% ï¼»23/48ï¼½, P = 0.027). At 1, 3, 6 and 12 months after surgery, the patients in group B also showed remarkably higher QOL scores than those in group B (2.61 ± 0.81 vs 2.12 ± 0.69, P = 0.005; 2.24 ± 0.66 vs 1.94 ± 0.51,P = 0.026; 2.12 ± 0.83 vs 1.80 ± 0.53,P = 0.047; and 1.94 ± 0.65 vs 1.72 ± 0.58, P = 0.038). CONCLUSION: Modified PKEP with complete preservation of the urethral mucosa in the 11－1 o'clock position can improve urinary continence, protect erectile function and ameliorate QOL in patients with BPH.

The immune response mechanism of Nilaparvata lugens against a combined infection of rice ragged stunt virus and Metarhizium anisopliae.

BACKGROUND: Previous studies of brown planthopper (BPH), Nilaparvata lugens, showed that carrying the plant pathogenic virus, rice ragged stunt virus (RRSV), enhanced the lethality of the entomopathogenic fungus, Metarhizium anisopliae (YTTR). The underlying mechanism for this was not established but a serine protease cascade was hypothesized to be involved. RESULTS: Two immune response genes, NlKPI and NlVenomase, were identified and shown to be involved. The synthesized double-strand RNA (dsRNA) techniques used in this study to explore gene function revealed that treatment with dsRNA to silence either gene led to a higher BPH mortality from M. anisopliae infection than the dsRNA control treatment. NlKPI and NlVenomase play vital roles in BPH immunity to defend against alien pathogens. Both genes participate in the immune response process of BPH against co-infection with RRSV and M. anisopliae YTTR by regulating the expression of antimicrobial peptides and phenoloxidase activity. CONCLUSION: Our study provided new targets for BPH biocontrol and laid a solid foundation for further research on the interaction of virus-insect-EPF (entomopathogenic fungus). © 2023 Society of Chemical Industry.

Relationship between 5' UTR length and gene expression pattern in chicken.

The chicken (Gallus gallus) is an important model organism that bridges the evolutionary gap between mammals and non-amniote vertebrates. Here, we carried out a systematic study of the relationship between 5' UTR length and gene expression pattern in the chicken genome. We found that gene 5' UTRs lengths show a negative correlation with gene expression levels and gene expression breadths significantly. The relevance of 5' UTR length to expression pattern can not be a consequence of transcription-associated mutations. We also found that gene 5' UTR length shows a weakly positive correlation with gene tissue specificity. Another intriguing finding is that genes with 5' UTR length <30 bp have highest expression level, highest expression breadth, and lowest tissue specificity in chicken. We argued that selection is likely involved in shaping 5' UTR length in the chicken genome.

Impact of GC content on gene expression pattern in chicken.

BACKGROUND: GC content varies greatly between different genomic regions in many eukaryotes. In order to determine whether this organization named isochore organization influences gene expression patterns, the relationship between GC content and gene expression has been investigated in man and mouse. However, to date, this question is still a matter for debate. Among the avian species, chicken (Gallus gallus) is the best studied representative with a complete genome sequence. The distinctive features and organization of its sequence make it a good model to explore important issues in genome structure and evolution. METHODS: Only nuclear genes with complete information on protein-coding sequence with no evidence of multiple-splicing forms were included in this study. Chicken protein coding sequences, complete mRNA sequences (or full length cDNA sequences), and 5' untranslated region sequences (5' UTR) were downloaded from Ensembl and chicken expression data originated from a previous work. Three indices i.e. expression level, expression breadth and maximum expression level were used to measure the expression pattern of a given gene. CpG islands were identified using hgTables of the UCSC Genome Browser. Correlation analysis between variables was performed by SAS Proprietary Software Release 8.1. RESULTS: In chicken, the GC content of 5' UTR is significantly and positively correlated with expression level, expression breadth, and maximum expression level, whereas that of coding sequences and introns and at the third coding position are negatively correlated with expression level and expression breadth, and not correlated with maximum expression level. These significant trends are independent of recombination rate, chromosome size and gene density. Furthermore, multiple linear regression analysis indicated that GC content in genes could explain approximately 10% of the variation in gene expression. CONCLUSIONS: GC content is significantly associated with gene expression pattern and could be one of the important regulation factors in the chicken genome.

LCN2 contributes to the improvement of nonalcoholic steatohepatitis by 8-Cetylberberine.

AIMS: Nonalcoholic steatohepatitis (NASH) is becoming one of the most common causes of liver transplantation and hepatocellular carcinoma, but no specific drugs are FDA-approved to treat it. 8-cetylberberine (CBBR), which is a long-chain alkane derivative of berberine, exhibits potent pharmacological activities and improves metabolism performance. The aim of this study is to explore the function and mechanism of CBBR against NASH. MATERIALS AND METHODS: L02 and HepG2 hepatocytes were treated with the medium containing palmitic acids and oleic acids (PO) and incubated with CBBR for 12 h, then the levels of lipid accumulation were tested by kits or western blots. C57BL/6 J mice were fed with a high-fat diet or a high-fat/high-cholesterol diet. CBBR (15 mg/kg or 30 mg/kg) was orally administered for 8 weeks. Liver weight, steatosis, inflammation, and fibrosis were evaluated. Transcriptomic indicated the target of CBBR in NASH. KEY FINDINGS: CBBR significantly reduced lipid accumulation, inflammation, liver injury, and fibrosis in NASH mice. CBBR also decreased lipid accumulation and inflammation in PO-induced L02 and HepG2 cells. RNA sequencing and bioinformatics analysis indicated that CBBR inhibited the pathways and key regulators associated with lipid accumulation, inflammation, and fibrosis in the pathogenesis of NASH. Mechanically, CBBR may prevent NASH via inhibiting LCN2, as proved by the finding that the anti-NASH effect of CBBR was more obvious in PO-stimulated HepG2 cells treated with LCN2 overexpression. SIGNIFICANCE: Our work provides an insight into the effectiveness of CBBR in improving metabolic-stress-caused NASH as well as the mechanism by regulating LCN2.

Berberine promotes IGF2BP3 ubiquitination by TRIM21 to induce G1/S phase arrest in colorectal cancer cells.

The increasing incidence of colorectal cancer (CRC) has become a major global public health burden. The natural drug Berberine (BBR) has shown potential in preventing CRC, and IGF2 mRNA binding protein 3 (IGF2BP3) may be a target of BBR. This study aims to investigate the mechanisms of BBR acting on IGF2BP3 to improve CRC. The results showed that IGF2BP3 played an important role in the development of CRC. BBR down-regulated IGF2BP3 expression and inhibited CRC growth in mice. Cell thermodynamic stability analysis (CETSA) and drug affinity responsive target stability (DARTS) analysis showed BBR may bind to IGF2BP3. BBR may induce structural changes in IGF2BP3 and decrease its protein stability in cytoplasm. The results from Co-Immunoprecipitation (Co-IP) suggested that BBR promoted the ubiquitination of IGF2BP3 by tripartite motif-containing protein 21 (TRIM21). Through RNA binding protein Immunoprecipitation (RIP) assay, it was found BBR inhibited the stabilization of CDK4/CCND1 mRNA by IGF2BP3 and promoted G1/S phase arrest in CRC cells. Overexpression of IGF2BP3 in vitro and in vivo attenuated the inhibition of CRC growth by BBR. This work demonstrated the potential of BBR targeting to IGF2BP3 in improving CRC and provided a new strategy for clinical treatment on CRC as well as novel anticancer drug design based on IGF2BP3 and TRIM21.

Epiberberine regulates lipid synthesis through SHP (NR0B2) to improve non-alcoholic steatohepatitis.

Epiberberine (EPI), extracted from Rhizome Coptidis, has been shown to attenuate hyperlipidemia in vivo. Herein we have studied the mechanism by which EPI is active against non-alcoholic steatohepatitis (NASH) using, mice fed on a methionine- and choline-deficient (MCD) diet and HepG2 cells exposed to free fatty acids (FFA). We show that small heterodimer partner (SHP) protein is key in the regulation of lipid synthesis. In HepG2 cells and in the livers of MCD-fed mice, EPI elevated SHP levels, and this was accompanied by a reduction in sterol regulatory element-binding protein-1c (SREBP-1c) and FASN. Therefore, EPI reduced triglyceride (TG) accumulation in steatotic hepatocytes, even in HepG2 cells treated with siRNA-SHP, and also improved microbiota. Thus, EPI suppresses hepatic TG synthesis and ameliorates liver steatosis by upregulating SHP and inhibiting the SREBP1/FASN pathway, and improves gut microbiome.

Protective effect of flavonoids extract of Hippophae rhamnoides L. on alcoholic fatty liver disease through regulating intestinal flora and inhibiting TAK1/p38MAPK/p65NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The therapeutic properties of Hippophae rhamnoides L. were already known in ancient Greece as well as in Tibetan and Mongolian medicine. Modern studies have indicated that Hippophae rhamnoides L. fermentation liquid protected against alcoholic fatty liver disease (AFLD). However, the underlying mechanism of Hippophae rhamnoides L. flavonoids extract (HLF) treating AFLD remains elusive. AIM OF THE STUDY: This study aimed to investigate the hepatoprotective effect of HLF in mice with AFLD and the interaction between AFLD and gut microbiota. MATERIALS AND METHODS: Chemical constituents of HLF were analyzed by Liquid Chromatography-Ion Trap-ESI-Mass Spectrometry. The Hepatoprotective effect of HLF was evaluated in mice with AFLD induced by alcohol (six groups, n = 10) daily at doses of 0.1, 0.2, and 0.4 g/kg for 30 consecutive days. At the end of experiment, mice were sacrificed and the liver, serum and feces were harvested for analysis. The liver histological changes were observed by H&E staining and oil red O staining. Moreover, the alterations of fecal microflora were detected by 16S rRNA gene sequencing. The inflammatory related genes were determined by qRT-PCR and western blotting respectively. RESULTS: The results showed that the oral administration of HLF remarkably alleviated hepatic lipid accumulation by decreasing the levels of ALT, AST, TG and TC. The levels of TNF-α, TGF-ß, and IL-6 were also reduced after treatment with HLF. Meanwhile, the protein and mRNA expression of NF-kB p65, MAPK p38 and TAK-1 in the liver of mice with AFLD were all reduced by HLF compared with model group. Furthermore, the 16S rRNA gene sequencing analysis demonstrated that HLF treatment can help restore the imbalance of intestinal microbial ecosystem and reverse the changes in Fimicutes/Bacterodietes, Clostridiales, Lachnospiraceae, S24-7, and Prevotella in mice with AFLD. CONCLUSION: HLF can effectively ameliorate liver injury in mice with AFLD, and regulate the composition of gut microbiota. Its regulatory mechanism may be related to TAK1/p38MAPK/p65NF-κB pathway. This study may provide novel insights into the mechanism of HLF on AFLD and a basis for promising clinical usage.

Seabuckthorn polysaccharide combined with astragalus polysaccharide ameliorate alcoholic fatty liver by regulating intestinal flora.

Background: At present, the incidence of alcoholic fatty liver disease (AFLD) is increasing year by year, and numerous studies have confirmed that liver diseases are closely related to intestinal flora. Seabuckthorn and Astragalus membranaceus, as traditional Chinese medicine (TCM) with the homology of medicine and food, have good liver protection, and their polysaccharides can regulate the intestinal flora. Here, we studied the effects of HRP, APS and the combination of the two polysaccharides on the intestinal flora of AFLD mice, which provided scientific basis for the treatment of AFLD with the two polysaccharides. Materials and methods: Thirty Kunming (KM) mice were randomly divided into the control group (Con), the model group (Mod), the HRP treatment group (HRP), the APS treatment group (APS), and HRP+APS treatment group (HRP+APS), with six mice in each group. The AFLD model was constructed by continuous intragastric administration of 42% vol Niulanshan ethanol solution for 28 days, and the mice in each polysaccharide group were given corresponding drugs. The levels of AST, ALT, TC and TG in serum of mice were measured. 16S rRNA amplicon sequencing technique was used to determine the diversity and richness of intestinal flora, and the relative abundance of intestinal flora at phylum level and genus level of the mice in each group. Results: HRP, APS and HRP+APS could reduce the serum levels of AST, ALT, TC and TG in mice. In addition, HRP, APS and HRP + APS restored the diversity, relative abundance and community structure of intestinal mucosa bacteria in AFLD mice to a certain extent. Specifically, HRP, APS and HRP+APS remarkably decreased the ratio of Firmicutes to Bacteroidetes, and ultimately increased the abundance of beneficial bacteria and reduced the abundance of pathogenic bacteria. Conclusion: HRP, APS, and HRP+APS can improve the intestinal microecology of AFLD model mice, alleviate liver injury, and maintain normal intestinal function in different degrees.

Xanthoceraside induces cell apoptosis through downregulation of the PI3K/Akt/Bcl-2/Bax signaling pathway in cell lines of human bladder cancer.

BACKGROUND: Xanthoceraside is a component obtained in the husks of Xanthoceras sorbifolia Bunge. Series of researches proved that xanthoceraside had functions of anti-inflammation and anti-tumor effects. However, the mechanisms of xanthoceraside against bladder cancer are unclear. Accordingly, we proposed to investigate xanthoceraside's impacts and potential mechanisms in cells of bladder cancer. METHODS: By using the CCK-8 assay, we measured the viability of cells. With the use of 4,6-diamidino-2-phenylindole (DAPI) staining, we examined nuclear fragmentation and chromatin condensation in the nuclei of apoptotic cells. By using flow cytometry, we measured cell apoptosis. By using Western blotting, we tested the expressions of Caspase-9, Caspase-8, Caspase-3, Bcl-xL, P53, and PI3K/Akt/Bcl-2/Bax. RESULTS: The proliferation of cell lines of human bladder cancer T24 and 5637 was suppressed by xanthoceraside significantly in a time- and concentration-dependent way. When cell lines 5637 and T24 were incubated as the xanthoceraside dose increased, the rates of cell apoptosis were upregulated, which was dependent on dose. According to further analysis, xanthoceraside induced apoptosis by upregulating Bax and downregulating the expression of Bcl-xL and Bcl-2. However, xanthoceraside did not change the expression of Caspase-9, Caspase-8, and Caspase-3. Interestingly, xanthoceraside also downregulated the expression of p-PI3K and p-Akt, and upregulated P53. CONCLUSIONS: Xanthoceraside induces cell apoptosis through downregulation of the PI3K/Akt/Bcl-2/Bax signaling pathway in cell lines of human bladder cancer.

Dual-energy CT angiography in the evaluation of intracranial aneurysms: image quality, radiation dose, and comparison with 3D rotational digital subtraction angiography.

OBJECTIVE: The purpose of this study was to evaluate the image quality, radiation dose, and diagnostic accuracy of dual-energy CT angiography (CTA) compared with 3D rotational digital subtraction angiography (DSA) in the detection of intracranial aneurysms. SUBJECTS AND METHODS: Forty-six patients with clinically suspected intracranial aneurysms underwent dual-source dual-energy CTA and 3D DSA. For the analysis of the image quality and radiation dose of dual-energy CTA, 46 patients who underwent digital subtraction CTA were recruited as a control group. The image quality of dual-energy CTA and digital subtraction CTA was rated on a 4-point scale as excellent, good, moderate, or poor. The radiation dose of CTA was recorded according to patient protocol. Aneurysm detection with dual-energy CTA compared with 3D DSA was analyzed on a per-patient and on a peraneurysm basis. Sensitivity, specificity, and positive and negative predictive values for aneurysm presence were determined. The mean maximum diameter and dome and neck dimensions of aneurysms were measured on dual-energy CTA and 3D DSA images. Correlation analysis between the two techniques was performed. RESULTS: There was no statistical difference between the image quality of dual-energy CTA and that of digital subtraction CTA (p>0.05). Patients undergoing dual-energy CTA received a smaller radiation dose (volume CT dose index, 20.6+/-0.1 mGy [mean+/-SD]; dose-length product, 398.6+/-19.0 mGy x cm) than those undergoing digital subtraction CTA (volume CT dose index, 50.4+/-3.4 mGy; dose-length product, 1,095.6+/-114.2 mGyxcm) (p<0.05). Three-dimensional DSA showed no aneurysm in 11 patients and 40 aneurysms in 35 patients. The mean maximum diameter of the aneurysms was 6+/-3 mm; the dome measurement, 5+/-3 mm; and the neck dimension, 3+/-2 mm. With dual-energy CTA, 38 aneurysms in 34 patients were correctly detected, and two aneurysms in two patients were missed. With DSA as the standard of reference, the sensitivity, specificity, and positive and negative predictive values of dual-energy CTA in the detection of intracranial aneurysm were 97.1%, 100%, 100%, and 91.7% on a per-patient basis and 95.0%, 100%, 100%, and 99.7% on a per-aneurysm basis. Dual-energy CTA had sensitivities of 93.8%, 100%, and 80.0% and specificities of 100%, 100%, and 100% in the detection of aneurysms larger than 5 mm, those measuring 3.1-5 mm, and aneurysms 3 mm or smaller. At dual-energy CTA, the mean maximum diameter and dome and neck dimensions were 6+/-3 mm, 5+/-3 mm, and 3+/-2 mm. Excellent correlation was found between DSA and dual-energy CTA findings with respect to mean maximum diameter and dome and neck dimensions (r=0.969, 0.957, and 0.870; p = 0.000). CONCLUSION: On the basis of the findings in the small series of patients evaluated, contrast-enhanced dual-energy CTA had diagnostic image quality at a lower radiation dose than digital subtraction CTA and high diagnostic accuracy compared with 3D DSA in the detection of intracranial aneurysms.

Automatic bone removal dual-energy CT angiography for the evaluation of intracranial aneurysms.

PURPOSE: To evaluate the diagnostic accuracy of dual-energy computed tomographic angiography (DE-CTA) in the detection of intracranial aneurysms and to determine whether DE-CTA provides adequate information to guide treatment choice. MATERIALS AND METHODS: Eighty patients (31 men and 49 women; mean [SD] ages of 52 [9] years) with spontaneous subarachnoid hemorrhage underwent DE-CTA. The performance of DE-CTA was compared with conventional CTA created from average weighted images and digital subtraction angiography (DSA). Sensitivity and specificity for aneurysm detection were determined on a per-patient and per-aneurysm basis. The treatment choice was assessed on the basis of aneurysm neck size and/or the dome/neck ratio. RESULTS: With DSA as reference standard (n = 61; 47 aneurysms in 41 patients), DE-CTA correctly detected 45 aneurysms in 41 patients corresponding to sensitivity and specificity of 100% and 95.0% on a per-patient basis versus 95.7% and 95.0% on a per-aneurysm basis, whereas conventional CTA correctly detected 43 aneurysms in 39 patients corresponding to sensitivity and specificity of 95.1% and 95.0% on a per-patient basis versus 91.5% and 95.0% on a per-aneurysm basis. No statistical difference between DE-CTA and conventional CTA was found for the diagnostic evaluation of intracranial aneurysms. Surgery was performed to treat 38 aneurysms, coiling in 26 aneurysms, stent in one patient, and follow-up in the remaining 5 aneurysms. Dual-energy CTA correctly predicted treatment choice in 44 aneurysms, with 15 aneurysms coiled and 29 aneurysms clipped. CONCLUSIONS: Compared with DSA, DE-CTA had a comparable diagnostic accuracy for the detection of intracranial aneurysms, visualization of the morphology of aneurysms at the skull base, and prediction of aneurysm treatment choice in most patients with spontaneous subarachnoid hemorrhage based on this study.

Indel segregating within introns in the chicken genome are positively correlated with the recombination rates.

Insertions and deletions (Indel) are important sources of genetic diversity and phenotypic divergence. Many factors such as mutation, recombination, selection and genetic drift can jointly affect the indel distribution across the genome. Studies of the relationship between recombination and indel density can, to a certain extent, reflect the selective constrain on indel. Based on the improved genetic map, genome sequence assembly and the partial (0.25X) shotgun sequencing of three breeds of domestic chicken, we calculated the recombination rates and the indel density segregating within introns and intergenic for 4 Mb windows (n = 210). Regression analyses demonstrated that recombination rates are significantly correlated with intron indel density, but not with the intergenic indel density. After adjusted regional effect, the significant trend was remained. This implies that selection is an important factor to influence the indel distribution within introns in chicken genome. By contrast, the intergenic indel seem to be neutral. Since the intron indel density on Z chromosome is less than half of that on autosomes, we preliminarily deduced that genetic hitchhiking might be more important than background selection in producing the observed correlation. As these two processes are not mutually exclusive, it is most likely that both contribute somewhat to the observed pattern. In result similar to previous study, we also found SNP density is highly correlated with indel density. Based on this characteristic, a hypothesis suggested that there are common effects of mutation and/or selection on the occurrence of indel and point mutations. This hypothesis can not explain our observations.

Altered Patterns of the Fractional Amplitude of Low-Frequency Fluctuation in Drug-Naive First-Episode Unipolar and Bipolar Depression.

Background: An early and correct diagnosis is crucial for treatment of unipolar depression (UD) and bipolar disorder (BD). The fractional amplitude of low-frequency fluctuations (fALFFs) has been widely used in the study of neuropsychiatric diseases, as it can detect spontaneous brain activities. This study was conducted to survey changes of fALFF within various frequency bands of the UD and BD patients, as well as to explore the effects on changes in fALFF on cognitive function. Methods: In total, 58 drug-naive first-episode patients, including 32 UD and 26 BD, were enrolled in the study. The fALFF values were calculated under slow-5 band (0.01-0.027 Hz) and slow-4 band (0.027-0.073 Hz) among UD patients, BD patients, and healthy control (HC). Additionally, we conducted correlation analyses to examine the association between altered fALFF values and cognitive function. Results: Under the slow-5 band, compared to the HC group, the UD group showed increased fALFF values in the right cerebellum posterior lobe, whereas the BD group showed increased fALFF values in the left middle temporal gyrus (MTG). Under the slow-4 band, in comparison to HC, the UD group showed increased fALFF values in the left superior temporal gyrus, whereas the right inferior parietal lobule (IPL) and BD group showed increased fALFF values in the bilateral postcentral gyrus. Notably, compared to BD, the UD group showed increased fALFF values in the right IPL under the slow-4 band. Furthermore, altered fALFF values in the left MTG and the right IPL were significantly positively correlated with Verbal Fluency Test scores. Conclusions: This current study indicated that there were changes in brain activities in the early UD and BD groups, and changes were related to executive function. The fALFF values can serve as potential biomarker to diagnose and differentiate UD and BD patients.

A clinically applicable deep-learning model for detecting intracranial aneurysm in computed tomography angiography images.

Intracranial aneurysm is a common life-threatening disease. Computed tomography angiography is recommended as the standard diagnosis tool; yet, interpretation can be time-consuming and challenging. We present a specific deep-learning-based model trained on 1,177 digital subtraction angiography verified bone-removal computed tomography angiography cases. The model has good tolerance to image quality and is tested with different manufacturers. Simulated real-world studies are conducted in consecutive internal and external cohorts, in which it achieves an improved patient-level sensitivity and lesion-level sensitivity compared to that of radiologists and expert neurosurgeons. A specific cohort of suspected acute ischemic stroke is employed and it is found that 99.0% predicted-negative cases can be trusted with high confidence, leading to a potential reduction in human workload. A prospective study is warranted to determine whether the algorithm could improve patients' care in comparison to clinicians' assessment.

Detection of pulmonary embolism by dual energy CT: correlation with perfusion scintigraphy and histopathological findings in rabbits.

The purpose of the study was to compare the ability of dual energy CT (DECT) and perfusion scintigraphy (PS) to detect pulmonary embolism (PE) in a rabbit model. Gelfoam (n = 20) or saline (n = 4) was injected into the femoral vein of rabbits. After 2 h, DECT pulmonary angiography (CTPA) was used to create blood flow imaging (BFI) and fusion images. The rabbits then underwent PS. Pathological determination of locations and numbers of lung lobes with PE was recorded. The sensitivity and specificity for BFI, CTPA, fused images and PS were calculated using the pathological results as reference standards. Compared with pathological evaluation, CTPA correctly identified PE in 40 lobes and absence of emboli in 80 lobes, corresponding to a sensitivity and specificity of 100%. BFI and fused images correctly identified PE in 40 lobes and the absence of emboli in 78 lobes, corresponding to a sensitivity and specificity of 100% and 98%, respectively. PS correctly detected 27 lobes with PE and 65 lobes without PE, corresponding to a sensitivity and specificity of 68% and 81%, respectively. BFI, CTPA and fused images derived from a single contrast-enhanced DECT provide a higher diagnostic accuracy of detecting PE than PS in a rabbit model.

A case report of oral contraceptive misuse induced cerebral venous sinus thrombosis and dural arteriovenous fistula.

RATIONALE: Consumption of oral contraceptive pills (OCP) is a known risk factor for cerebral venous sinus thrombosis (CVST) among women. Development of dural arteriovenous fistula (dAVF) afterwards was very uncommon. We present a rare chronic complication of development of dAVF after CVST. PATIENT CONCERNS: A 22-year-old woman suffered headache for a week. She was then admitted into our hospital. DIAGNOSIS: Contrast enhanced magnetic resonance venography (MRV) demonstrated the thrombosis of the left transverse-sigmoid sinus the second day. INTERVENTIONS: The intravenous thrombolysis was carried out. As the symptoms improved, the patient was discharged, while the treatment with oral dabigatran continued. However, 3 months after the onset, magnetic resonance imaging (MRI) showed swelling brainstem, and digital subtraction angiography (DSA) confirmed a dAVF. Clipping of the fistula was conducted, and her clinical symptoms improved gradually. OUTCOMES: The patient was transferred to rehabilitation center later, and received follow-up care. LESSONS: When a patient taking OCP and suffering from a sudden headache, a clinical suspicion of possible CVST should always arise to avoid the onset of dAVF as soon as possible.

The Radiological Imaging Features of Easily Misdiagnosed Epithelioid Glioblastoma in Seven Patients.

OBJECTIVE: We review the radiological imaging features and report histopathological findings of 7 adult patients with epithelioid glioblastoma (eGBM), which was a newly revised subtype of glioblastoma. METHODS: Seven adult patients with a diagnosis of eGBM on a brain tissue specimen were retrospectively confirmed by pathology. The tumor magnetic resonance imaging characteristics such as location, number, edema, necrosis, hemorrhage, enhancement, diffusion-weighted image, apparent diffusion coefficient, magnetic resonance spectroscopy, dynamic susceptibility contrast-perfusion-weighted imaging, and histopathological findings were documented. RESULTS: The tumors of these patients exhibited iso-hyperintensive signal on the T2-weighted image and iso-hypointensive signal on the T1-weighted image. All the lesions manifested iso-hypointensive signal on the diffusion-weighted image, and 2 cases showed significantly restricted hyperintensive signal (2/7). Peritumoral edema in all cases was mild. Five cases were located in the cortical lobe (5/7) and the other 2 were multifocal (2/7). Four cases showed white matter collapse sign (4/7). These tumors revealed apparent enhancement after contrast injection. In particular, 4 cases displayed capsuled sign (4/7), 2 cases showed dura mater tail sign (2/7), and 1 case showed hemorrhage (1/7). The mean value of apparent diffusion coefficient in 6 cases was 1.09 × 10-3 mm2/s. The mean value of relative cerebral blood volume in 3 cases was 2.84 × 10-3 mm2/s on dynamic susceptibility contrast-perfusion-weighted imaging. The average value of the choline/N-acetyl aspartate ratio in 4 cases was 6.47 × 10-3 mm2/s on magnetic resonance spectroscopy. All cases expressed a BRAF V600E mutation according to molecular characteristics. CONCLUSIONS: eGBMs that were predominantly located in cortex with mild peritumoral edema, white matter collapse, encapsular sign, and dura mater tail sign could be easily misdiagnosed as cortex-involved intracranial brain tumor such as meningioma, whereas multifocal tumors could be easily misdiagnosed as metastatic tumor and lymphoma. Multimodal images were helpful for the differential diagnosis.