Effects of baculovirus infection on intestinal microflora of BmNPV resistant and susceptible strain silkworm.

Bombyx mori L. (Lepidoptera: Bombycidae) nucleopolyhedrovirus (BmNPV) is a serious pathogen causing huge economic losses to sericulture. There is growing evidence that the gut microbiota of silkworms plays a critical role in shaping host responses and interactions with viral infection. However, little is known about the differences in the composition and diversity of intestinal microflora, especially with respect to silkworm strain differences and BmNPV infection-induced changes. Here, we aim to explore the differences between BmNPV-resistant strain A35 and susceptible strain P50 silkworm and the impact of BmNPV infection on intestinal microflora in different strains. The 16S rDNA sequencing analysis revealed that the fecal microbial populations were distinct between A35 and P50 and were significantly changed post BmNPV infection in both strains. Further analysis showed that the BmNPV-resistant strain silkworm possessed higher bacterial diversity than the susceptible strain, and BmNPV infection reduced the diversity of intestinal flora assessed by feces in both silkworm strains. In response to BmNPV infection, the abundance of Muribaculaceae increased in P50 and decreased in A35, while the abundance of Enterobacteriaceae decreased in P50 and increased in A35. These results indicated that BmNPV infection had various effects on the abundance of fecal microflora in different silkworm strains. Our findings not only broadened the understanding of host-pathogen interactions but also provided theoretical help for the breeding of resistant strains and healthy rearing of silkworms based on symbiotic bacteria.

Bmo-miR-3351 modulates glutathione content and inhibits BmNPV proliferation by targeting BmGSTe6 in Bombyx mori.

MicroRNAs (miRNAs) are small non-coding RNAs that play pivotal roles in the host response to invading pathogens. Among these pathogens, Bombyx mori nucleopolyhedrovirus (BmNPV) is one of the main causes of substantial economic losses in sericulture, and there are relatively few studies on the specific functions of miRNAs in the B. mori-BmNPV interaction. Therefore, we conducted transcriptome sequencing to identify differentially expressed (DE) messenger RNAs (mRNAs) and miRNAs in the midgut of 2 B. mori strains (BmNPV-susceptible strain P50 and BmNPV-resistant strain A35) after BmNPV infection. Through correlation analysis of the miRNA and mRNA data, we identified a comprehensive set of 21 miRNAs and 37 predicted target mRNAs. Notably, miR-3351, which has high expression in A35, exhibited remarkable efficacy in suppressing BmNPV proliferation. Additionally, we confirmed that miR-3351 binds to the 3' untranslated region (3' UTR) of B. mori glutathione S-transferase epsilon 6 (BmGSTe6), resulting in its downregulation. Conversely, BmGSTe6 displayed an opposite expression pattern to miR-3351, effectively promoting BmNPV proliferation. Notably, BmGSTe6 levels were positively correlated with glutathione S-transferase activity, consequently influencing intracellular glutathione content in the infected samples. Furthermore, our investigation revealed the protective role of glutathione against BmNPV infection in BmN cells. In summary, miR-3351 modulates glutathione content by downregulating BmGSTe6 to inhibit BmNPV proliferation in B. mori. Our findings enriched the research on the role of B. mori miRNAs in the defense against BmNPV infection, and suggests that the antiviral molecule, glutathione, offers a novel perspective on preventing viral infection in sericulture.

Regulation of Bombyx mori ferritin heavy-chain homolog on ROS induces multiple effects on BmNPV replication.

Ferritin is an iron-binding protein composed of light-chain and heavy-chain homologs with a molecular weight of about 500 kDa. Free iron ions significantly affect reactive oxygen species (ROS) accumulation. Previous research has shown that Bombyx mori nucleopolyhedrosis virus (BmNPV) can increase ROS accumulation, activate autophagy, induce apoptosis, and upregulate the expression of B. mori ferritin heavy-chain homolog (BmFerHCH). However, the mechanism of mutual regulation between BmFerHCH and ROS-mediated autophagy and apoptosis induced by BmNPV remains unclear. In this study, we found that BmNPV induced the time-dependent accumulation of ROS in BmN cells, thereby promoting BmFerHCH expression. Interestingly, in BmFerHCH-overexpressed cells, BmNPV replication was inhibited in the first 18 h after infection but stimulated after 24 h. Further research on H2O2 or antioxidant-treated cells indicated that ROS-induced autophagy slightly increased in the early infection stage and increased BmNPV replication, while in the late stage, a large accumulation of ROS induced apoptosis and inhibited BmNPV replication. In this process, BmFerHCH inhibits BmNPV-induced ROS accumulation by chelating Fe2+. Taken together, BmFerHCH regulates ROS-mediated autophagy and apoptosis to achieve its various effects on BmNPV replication. These findings will help elucidate BmNPV-induced autophagy and apoptosis mediated by ROS and BmFerHCH, as well as the mutually fighting relationship between viruses and hosts.

Impact of metacognition on attitudes toward epilepsy in medical students.

PURPOSE: This study evaluated medical students' knowledge and attitudes toward epilepsy and the influence of metacognition thereon. METHOD: Valid questionnaires were administered to medical students including undergraduate, professional postgraduate, and standardized residency training students (N = 503). The questionnaire had 4 parts: demographic information, knowledge of epilepsy, attitudes toward epilepsy, and metacognitive assessment. The Chinese Public Attitudes Toward Epilepsy scale and 30-Item Metacognition Questionnaire were used to assess attitudes and metacognition, respectively. RESULTS: Almost all participants had heard of epilepsy; 38.8% had witnessed a seizure and 25% were acquainted with a person with epilepsy. The proportion of correct answers to epilepsy-related knowledge ranged from 40.6% (Putting an object into the mouth of a person experiencing an epileptic seizure) to 97% (Convulsion is a symptom of epilepsy). However, knowledge of epilepsy was not able to affect attitudes toward epilepsy. Age, years of clinical experience, having witnessed a seizure, positive belief of worry, and need to control thinking were correlated with the different domains of attitude toward epilepsy. When participants were divided into 2 groups-i.e., those with high and low knowledge of epilepsy, participants in the former group who had a positive belief of worry or had not witnessed any seizures were more likely to have negative attitudes toward epilepsy. CONCLUSION: Medical students showed good awareness of the etiology and symptoms of epilepsy. Overall, attitudes toward epilepsy were negative. A positive belief of worry was associated with a more negative attitude toward epilepsy among respondents with greater knowledge of epilepsy.

Trehalose hydrolysis and transport-related genes promote Bombyx mori nucleopolyhedrovirus proliferation through the phosphoinositide 3-kinase-Akt signalling pathway in BmN cell.

The reprogramming of host physiology has been considered an essential process for baculovirus propagation. Trehalose, the main sugar in insect blood, plays a crucial role as an instant energy source. Although the trehalose level is modulated following infection with Bombyx mori nucleopolyhedrovirus (BmNPV), the mechanism of trehalose metabolism in response to BmNPV infection is still unclear. In this study, we demonstrated that the trehalose level tended to be lower in BmNPV-infected hemolymph and higher in the midgut. The omics analysis revealed that two trehalose transporters, BmTret1-1 and BmTret1-2, and trehalase, BmTRE1 and BmTRE2, were differentially expressed in the midgut after BmNPV infection. BmTret1-1 and BmTret1-2 had the ability to transport trehalose into the cell and promoted cellular absorption of trehalose. Furthermore, the functions of BmTret1-1, BmTret1-2, BmTRE1 and BmTRE2 in BmNPV infection were analyzed. These genes were upregulated in the midgut after BmNPV infection. Virus amplification analysis revealed that these genes could promote BmNPV proliferation in BmN cells. In addition, these genes could promote the expression of BmPI3K, BmPDK1 and BmAkt and inhibit the expression of BmFoxO in the phosphoinositide 3-kinase (PI3K)-Akt signalling pathway. Similarly, the increased trehalose level in BmN cells could promote the expression of BmPI3K, BmPDK1 and BmAkt and inhibit the expression of BmFoxO. Taken together, BmNPV infection promote the expression of trehalose hydrolysis and transport-related genes. These changes affect the PI3K-Akt signalling pathway to facilitate BmNPV proliferation. These findings help clarify the relationship between trehalose metabolism and BmNPV infection.

Fibroblasts overpressing WNT2b cause impairment of intestinal mucosal barrier / 南方医科大学学报

OBJECTIVE@#To investigate the mechanism by which fibroblasts with high WNT2b expression causes intestinal mucosa barrier disruption and promote the progression of inflammatory bowel disease (IBD).@*METHODS@#Caco-2 cells were treated with 20% fibroblast conditioned medium or co-cultured with fibroblasts highly expressing WNT2b, with the cells without treatment with the conditioned medium and cells co-cultured with wild-type fibroblasts as the control groups. The changes in barrier permeability of Caco-2 cells were assessed by measuring transmembrane resistance and Lucifer Yellow permeability. In Caco-2 cells co-cultured with WNT2b-overexpressing or control intestinal fibroblasts, nuclear entry of β-catenin was detected with immunofluorescence assay, and the expressions of tight junction proteins ZO-1 and E-cadherin were detected with Western blotting. In a C57 mouse model of dextran sulfate sodium (DSS)-induced IBD-like enteritis, the therapeutic effect of intraperitoneal injection of salinomycin (5 mg/kg, an inhibitor of WNT/β-catenin signaling pathway) was evaluated by observing the changes in intestinal inflammation and detecting the expressions of tight junction proteins.@*RESULTS@#In the coculture system, WNT2b overexpression in the fibroblasts significantly promoted nuclear entry of β-catenin (P < 0.01) and decreased the expressions of tight junction proteins in Caco-2 cells; knockdown of FZD4 expression in Caco-2 cells obviously reversed this effect. In DSS-treated mice, salinomycin treatment significantly reduced intestinal inflammation and increased the expressions of tight junction proteins in the intestinal mucosa.@*CONCLUSION@#Intestinal fibroblasts overexpressing WNT2b causes impairment of intestinal mucosal barrier function and can be a potential target for treatment of IBD.

Mechanism of intestinal injury induced by WNT2B high-expressed fibroblasts in Crohn's disease / 中华儿科杂志

Objective: To explore the mechanism of intestinal tissue damage induced by macrophages activated by WNT2B high-expressed fibroblasts. Methods: This study involved biological information analysis, pathological tissue research and cell experimental research. The biological information of the colon tissue from the children with inflammatory bowel disease in previous study was analyzed again with single-cell sequencing. The pathological tissues were collected by colonoscopy from 10 children with Crohn's disease treated in the Department of Gastroenterology of Guangzhou Women and Children's Medical Center from July 2022 to September 2022. According to the findings of colonoscopy, tissues with obvious inflammation or ulceration were classified as the inflammatory group, while tissues with slight inflammation and no ulceration were classified as the non-inflammatory group. HE staining was performed to observe the pathological changes of the colon tissues. Macrophage infiltration and CXCL12 expression were detected by immunofluorescence. In terms of cell experiments, fibroblasts transfected with WNT2B plasmid or empty plasmid were co-cultured with salinomycin treated or non-treated macrophages, respectively; the expression of proteins through Wnt classical pathway were detected by western blotting. Macrophages treated with SKL2001 were used as the experimental group, and those with phosphate buffer as the control group. The expression and secretion of CXCL12 in macrophages were detected by quantitative Real-time PCR and enzyme-linked immunosorbent assay (ELISA). T-test or rank sum test were used for the comparison between groups. Results: Single-cell sequencing analysis suggested that macrophages were the main cells in inflammatory bowel disease colon tissue, and there was interaction between WNT2B high-expressed fibroblasts and macrophages. HE staining of the 10 patients ((9.3±3.8) years old, 7 males and 3 females) showed that the pathological score of colon tissue in the inflammatory group was higher than that in the non-inflammatory group (4 (3, 4) vs. 2 (1, 2) points, Z=3.05, P=0.002). Tissue immunofluorescence indicated that the number of infiltrating macrophages in the inflammatory group was significantly higher than that in the non-inflammatory group under high power field of view (72.8±10.4 vs.8.4±3.5, t=25.10, P<0.001), as well as the number of cells expressing CXCL12 (14.0±3.5 vs. 4.7±1.9, t=14.68, P<0.001). In cell experiments, western blotting suggested an elevated level of glycogen synthase kinase-3β phosphorylation in macrophages co-cultured with fibroblast transfected with WNT2B plasmid, and salinmycin could reverse this change. Real-time PCR suggested that the transcription level of CXCL12 in the experimental group was higher than that in the control group (6.42±0.04 vs. 1.00±0.03, t=183.00, P<0.001), as well as the expression and secretion of CXCL12 by ELISA ((465±34) vs. (77±9) ng/L, t=13.21, P=0.006). Conclusion: WNT2B high-expressed fibroblasts can secrete WNT2B protein and activate the Wnt classical signaling pathway thus enhancing the expression and secretion of CXCL12 in macrophages, inducing the development of intestinal inflammation of Crohn's disease.

Meranzin Hydrate Improves Depression-Like Behaviors and Hypomotility via Ghrelin and Neurocircuitry / 中国结合医学杂志

OBJECTIVE@#To investigate whether meranzin hydrate (MH) can alleviate depression-like behavior and hypomotility similar to Chaihu Shugan Powder (CSP), and further explore the potential common mechanisms.@*METHODS@#Totally 120 Spraque-Dawley rats were randomly divided into 5-8 groups including sham, vehicle, fluoxetine (20 mg/kg), mosapride (10 mg/kg), CSP (30 g/kg), MH (9.18 mg/kg), [D-Lys3]-GHRP-6 (Dlys, 0.5 mg/kg), and MH+Dlys groups by a random number table, 8 rats in each group. And 32 mice were randomly divided into wild-type, MH (18 mg/kg), growth hormone secretagogue receptor-knockout (GHSR-KO), and GHSR+MH groups, 8 mice in each group. The forced swimming test (FST), open field test (OFT), tail suspension test (TST), gastric emptying (GE) test, and intestinal transit (IT) test were used to assess antidepressant and prokinetic (AP) effects after drug single administration for 30 min with absorbable identification in rats and mice, respectively. The protein expression levels of brain-derived neurotrophic factor (BDNF) and phosphorylated mammalian target of rapamycin (p-mTOR) in the hippocampus of rats were evaluated by Western blot. The differences in functional brain changes were determined via 7.0 T functional magnetic resonance imaging-blood oxygen level-dependent (fMRI-BOLD).@*RESULTS@#MH treatment improved depression-like behavior (FST, OFT) and hypomotility (GE, IT) in the acute forced swimming (FS) rats (all P<0.05), and the effects are similar to the parent formula CSP. The ghrelin antagonist [D-Lys3]-GHRP-6 inhibited the effect of MH on FST and GE (P<0.05). Similarly, MH treatment also alleviated depression-like behavior (FST, TST) in the wild-type mice, however, no effects were found in the GHSR KO mice. Additionally, administration of MH significantly stimulated BDNF and p-mTOR protein expressions in the hippocampus (both P<0.01), which were also prevented by [D-Lys3]-GHRP-6 (P<0.01). Besides, 3 main BOLD foci following acute FS rats implicated activity in hippocampus-thalamus-basal ganglia (HTB) circuits. The [D-Lys3]-GHRP-6 synchronously inhibited BOLD HTB foci. As expected, prokinetic mosapride only had effects on the thalamus and basal ganglia, but not on the hippocampus. Within the HTB, the hippocampus is implicated in depression and FD.@*CONCLUSIONS@#MH accounts for part of AP effects of parent formula CSP in acute FS rats, mainly via ghrelin-related shared regulation coupled to BOLD signals in brain areas. This novel functionally connection of HTB following acute stress, treatment, and regulation highlights anti-depression unified theory.

Bombyx mori ferritin heavy-chain homolog facilitates BmNPV proliferation by inhibiting reactive oxygen species-mediated apoptosis.

Ferritin heavy-chain homolog (FerHCH), an iron-binding protein, plays an important role in the host defense against oxidative stress and pathogen infections. In our previous research, Bombyx mori native ferritin had an interaction with B. mori nucleopolyhedrovirus (BmNPV). However, the underlying molecular mechanism of single ferritin homolog responses to BmNPV infection remains unclear. In this study, we found that BmNPV titer and B. mori FerHCH (BmFerHCH) expression were positively correlated with the ferric iron concentration. We performed RNA interference (RNAi) and overexpression experiments to investigate the effects of BmFerHCH on BmNPV proliferation. BmFerHCH knockdown suppressed BmNPV proliferation in vivo and in vitro, whereas BmFerHCH overexpression facilitated BmNPV proliferation. In addition, the oxidative stress level was increased significantly in BmN cells after budded virus infection, while BmFerHCH could neutralize the increased ROS production induced by BmNPV. Of note, we found that ROS was involved in BmNPV-induced apoptosis. Through inhibiting ROS, apoptosis was suppressed by BmFerHCH, whereas BmFerHCH knockdown facilitated apoptosis. Therefore, we hypothesize that BmFerHCH-mediated inhibition of virus-induced apoptosis depends on suppressing ROS accumulation and, thereby, facilitates virus replication. These results suggest that BmFerHCH plays an important role in facilitating BmNPV proliferation and modulating BmFerHCH is potential strategy for studying host-pathogen interactions.

Analysis of Radial Peripapillary Capillary Density in Patients with Bietti Crystalline Dystrophy by Optical Coherence Tomography Angiography / 生物医学与环境科学（英文）

OBJECTIVE@#We wanted to investigate the radial peripapillary capillary (RPC) network in patients with Bietti crystalline dystrophy (BCD).@*METHODS@#We compared RPC densities in the disk and different peripapillary regions, obtained using optical coherence tomography angiography in 22 patients with BCD (37 eyes) and 22 healthy subjects (37 eyes). The BCD group was then divided into Stage 2 and Stage 3 subgroups based on Yuzawa staging, comparing the RPC densities of the two.@*RESULTS@#The disk area RPC density was 38.8% ± 6.3% in the BCD group and 49.2% ± 6.1% in the control group ( P < 0.001), and peripapillary region RPC density was significantly lower in the BCD group than in the control group (49.1% ± 4.7% and 54.1% ± 3.0%, respectively, P < 0.001). There were no significant RPC density differences between the tempo quadrant and inside disk of Stages 2 and 3 subgroups; the other areas showed a significantly lower RPC density in Stage 3 than in Stage 2 BCD.@*CONCLUSION@#The BCD group RPC density was significantly lower than the control group. The reduction of RPC density in the tempo quadrant occurred mainly in the Stage 1 BCD. In contrast, the reduction of RPC density in superior, inferior, and nasal quadrants occurred mainly in Stage 2.

[Removal Performance of Antibiotic Resistance Genes and Heavy Metal Resistance Genes in Municipal Wastewater by Magnetic-Coagulation Process].

Antibiotic resistance genes (ARGs) in municipal wastewater pose a potential threat to the environment. In this study, the change in absolute and relative abundance of ARGs, metal resistance genes (MRGs), and mobile genetic elements (MGTs) were investigated during an emergent municipal wastewater treatment by the magnetic separation process. Results indicate that all the concentrations of targeted ARGs, MRGs, and MGTs decreased significantly in the primary and secondary stirring tank. However, the absolute abundance of some ARGs and MRGs increased in the effluent, which is likely caused by the presence of ample MGTs, in the order of int1 (2.00×1010 copies·mL-1) > int2 (1.91×108 copies·mL-1) > Tn 916/1545e(5.38×108 copies·mL-1). The results obtained from network and PCA analysis showed that the removal of ARGs and MRGs were significantly associated with variations in the microbial community and common pollutants in urban wastewater, such as suspended solids, phosphorus, and COD, which are important factors for affecting the removal efficiency of antibiotic resistance genes and metal heavy resistance genes. These results show that magnetic separation can effectively reduce common pollutants in urban wastewater and might further restrict the transmission and transfer of ARGs. Moreover, it is necessary to strengthen the subsequent management of magnetic separation effluent and dehydrated sludge by disinfection technologies to lessen the risk of antimicrobial contamination.

The predictive value and efficacy of the risk model based on the metabolic parameters of 18F-FDG PET-CT for EGFR gene mutations in non-small cell lung cancer / 中华放射学杂志

Objective:To explore the value and efficacy of the risk model based on the metabolic parameters of 18F-FDG PET-CT in predicting epidermal growth factor receptor (EGFR) gene mutations in non-small cell lung cancer (NSCLC). Methods:This retrospectives study reviewed 105 NSCLC patients who were tested for EGFR gene expression and underwent 18F-FDG PET-CT exam prior to treatment from Jan 2017 to June 2018 in our hospital. The patients were divided into EGFR mutations group ( n=40) and EGFR wild type group ( n=65). The differences between the different groups were analyzed in several clinical characteristics and three metabolic parameters based on 18F-FDG PET-CT, including the maximal standard uptake value (SUV max), metabolic tumor volume (MTV), total lesion glycolysis (TLG) of the primary tumor. Multivariate logistic regression analysis was performed to identify predictors of EGFR mutations, and the risk prediction model and nomogram graph were constructed. Diagnostic efficiency of the model was done by the receiver operating characteristics (ROC) curve analysis, and the Calibration plot was performed by Hosmer-Lemeshow (H-L) test to evaluate the calibration scale of the model. Results:There were statistically significant differences in gender, smoking status, serum CEA level, length of tumor, pathological types, TTF-1 and NapsinA expression between the EGFR mutant groups and EGFR wild-type groups (all P<0.05). The MTV and TLG of EGFR mutation group were 4.4 (4.5，37.1) cm 3 and 46.6 (21.2，118.2), respectively. The MTV and TLG of EGFR wild type group were 7.4 (3.2，13.5) cm 3 and 95.4 (26.4，345.1), respectively. The MTV and TLG of EGFR mutation group were significantly lower than those of EGFR wild type group ( Z=-2.452, P=0.014; Z=-2.379, P=0.017). ROC curve analysis showed area under the curve (AUC) predicted by SUV max, MTV and TLG for EGFR mutations was 0.597, 0.643 and 0.639, respectively. Multivariate analysis demonstrated that gender, length of tumor, SUV max and MTV were independent predictors of EGFR mutations, with the odds ratio (OR) values (95 %CI) as 3.811 (1.508-9.629), 1.679 (0.899-3.136), 0.928 (0.848-1.015) and 0.924 (0.865-0.986), respectively. The predictive model and nomogram graph was established, with the sensitivity, specificity, positive predictive value, negative predictive value and AUC of 80.0%, 66.2%, 68.8%, 75.3% and 0.775 (0.687-0.864), respectively. The H-L test showed the model had excellent accuracy (χ 2=3.872, P=0.869). Conclusion:The risk model based on the metabolic parameters of 18F-FDG PET-CT has a good performance in predicting the mutations of EGFR gene in patients with NSCLC.

Interleukin-11 treatment protected against cerebral ischemia/reperfusion injury.

OBJECTIVE: Inflammation and immune responses are crucial factors associated with the onset and progression of stroke. Interleukin-11 (IL-11) is a hematopoietic IL-6 family cytokine that functions as an anti-inflammatory agent against various inflammatory diseases. However, its roles in stroke remain unknown. In this study, we investigated the effects of IL-11 on cerebral ischemia-reperfusion injury in a model of focal cerebral ischemia. METHODS: Mice were randomly divided into five groups the vehicle group, the middle cerebral artery occlusion (MCAO) group, the MCAO plus adenosine monophosphate-activated protein kinase (AMPK) inhibitor compound C group, the MCAO plus IL-11 treatment group, and the MCAO plus IL-11 treatment and compound C group. Focal cerebral ischemia was induced by occluding the left middle cerebral artery, and reperfusion was achieved by withdrawing the suture 2 h after ischemia. The protein expression levels of IL-11 were measured using Western blot analysis, and its location was detected using immunohistochemistry and immunofluorescence staining. The infarct volume was examined using 2,3,5-triphenyl tetrazolium chloride (TTC) staining, and the neurobehavioral progression was assessed using the neurological scoring system. The expression of astrocytes and microglia was detected using immunochemistry, and real-time quantitative PCR was used for the gene quantification of inflammatory cytokines. The extent of cerebral ischemia-reperfusion injury was tested using Nissl staining and the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay. The expression of the apoptotic proteins Bax, Bcl-2 and cleaved caspase-3 were detected using Western blot analysis, and the oxidative stress was also measured. RESULTS: The expression of IL-11 mRNA and protein significantly decreased after cerebral ischemia. Immunohistochemical staining showed a large amount of IL-11 in the cerebral cortex of the mice in the vehicle group, whereas the immunoreactivity of IL-11 remained weak for 24 h in the MCAO group. Immunofluorescent staining further confirmed that IL-11 was mainly expressed in the neurons. It was suggested that IL-11 (20 µg/kg) treatment ameliorated infarction and reduced neurological scores. In addition, IL-11 proved to reduce neuropathic damage, glial activation, and the expression of proinflammatory cytokines and increase the expression of anti-inflammatory cytokines after cerebral ischemia. IL-11 was also able to alleviate oxidative stress caused by cerebral ischemia, and AMPK inhibition enhanced the alleviation. Moreover, IL-11 was found to inhibit apoptosis caused by cerebral ischemia, which could also be facilitated by AMPK inhibitors. SIGNIFICANCE: Our research suggests that IL-11 is decreased during cerebral ischemia-reperfusion injury, but IL-11 treatment can improve neurological function and reduce the cerebral infarct volume, which can trigger stroke in mice. AMPK inhibition can further promote the protective effect of IL-11 in stroke. Overall, we demonstrate that IL-11 is of therapeutic interest in controlling stroke and managing cerebral ischemia-reperfusion injury.

Benign metastasizing leiomyoma: A case report andliterature review / 中南大学学报(医学版)

Benign metastasizing leiomyoma (BML) often occurs in women with a history of uterine leiomyoma at the childbearing age. At the same time, BML cases with multiple sites of metastatic lesions are extremely rare. A BML patient with multiple metastases of uterine leiomyoma in two lung and lumbar spine after surgery was admitted to Department of Spinal Surgery, Second Xiangya Hospital, Central South University in September 2017. Positron emission tomography/computed tomography (PET/CT) can perform a whole body examination for BML patients, which can find metastases in many parts of the body such as lung, abdominal cavity, pelvic cavity and spine. The PET/CT results are helpful to a comprehensive diagnosis. The imaging and clinical features of BML are now explored in combination with the characteristics of the case and relevant literature reports.

Neuroglobin promotes the proliferation and suppresses the apoptosis of glioma cells by activating the PI3K/AKT pathway.

Our previous study demonstrated that neuroglobin (Ngb) functions as an independent predictive indicator of the prognosis of patients with glioma and promotes cancer cell growth by suppressing apoptosis. However, the understanding of the mechanisms underlying the survival­enhancing function of Ngb in glioma is limited. In the present study, KEGG PathwayFinder by gene correlation analysis was performed on the R2: Genomics Analysis and Visualization Platform, which revealed a high association between Ngb and the phosphatidylinositol 3­kinase (PI3K)/AKT pathway using glioma data (GSE4290) from the Gene Expression Omnibus database. Furthermore, western blotting experiments were performed in U251 and U87 glioma cells, and Ngb knockdown using short hairpin RNA reduced the protein levels of phosphorylated (p)­AKT, p­mammalian target of rapamycin (mTOR) and antiapoptotic factor Bcl­2, and increased the expression of the proapoptotic protein Bcl­2­associated X, in U251 cells. In addition, Ngb overexpression promoted the activation of the PI3K/AKT pathway in U87 cells. MK2206, a PI3K/AKT signaling inhibitor, reduced the expression of p­AKT and increased the levels of apoptosis­associated proteins, including cleaved poly(ADP­ribose) polymerase 1 and cleaved caspase­3/7/8, in Ngb­overexpressing U87 cells. Furthermore, MK2206 treatment reduced the proliferation and induced the apoptosis of Ngb­overexpressing U87 cells, as indicated by the results of MTT, colony formation and flow cytometry assays. In addition, insulin­like growth factor­1, a PI3K/AKT signaling activator, reversed Ngb knockdown­induced growth arrest and apoptosis in U251 cells. In conclusion, the results of the present study indicate that Ngb may facilitate a malignant phenotype of glioma cells by activating the PI3K/AKT pathway.

18F-FDG PET/CT features on paraganglioma of testis with multiple lymph node and lung metastasis: A case report and literature review / 中南大学学报(医学版)

To determine the clinicopathological and imaging features in 18F-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography and computed tomography (PET/CT) for paraganglioma of testis, and to increase the diagnostic accuracy.
 Methods: A case of paraganglioma of testis with multiple lymph node and lung metastasis were reported. PET/CT and pathological findings in the case were retrospectively analyzed.
 Results: The patient presented with high blood pressure, high level of catecholamine, and urinary vanillylmandelic acid. The patient underwent 18F-FDG PET/CT, which showed the features including the right testis nodule with a star lesion nearby, the right spermatic cord, the lymphadenopathy of bilateral inguinal and retroperitoneum, the posterior basal segment of right lung nodule, and a lot of brown adipose tissues (BAT) in the whole body with intense FDG uptake. 18F-FDG PET/CT showed that the intense FDG uptake of the BAT disappeared after the excision of the right testis and metastasis of paraganglioma.
 Conclusion: PET/CT shows great value in localization diagnose, clinical staging and curative evaluation. PET/CT plays a helpful role in revealing the BAT with 18F-DG avidity in the patients with paraganglioma with elevated blood pressure, high level catecholamine, and urinary vanillylmandelic acid.

Looking back: forward looking.

GigaScience is now 5 years old, having been launched at the 2012 Intelligent Systems for Molecular Biology conference. Anyone who has attended what is the largest computational biology conference since then has had the opportunity to join us for each birthday celebration-and receive 1 of our fun T-shirts as a party prize. Since launching, we have pushed our agenda of openness, transparency, reproducibility, and reusability. Here, we look back at our first 5 years and what we have done to forward our open science goals in scientific publishing. Our mainstay has been to create a process that allows the availability and publication of as many "research objects" as possible to create a more complete way of communicating how the research process is done.

Comparative research of setup error and registration for image-guided radiotherapy of lung cancer / 医疗卫生装备

Objective To explore the setup error and area registration error during lung cancer radiotherapy by using the on board imager (OBI) of the linear accelerator. Methods Totally 50 lung cancer patients underwent image-guided radiation therapy. Then OBI system was used for the scan validation by electronic portal imaging device (EPID) and cone beam CT (CBCT), and comparative analysis was executed on the setup errors of EPID and CBCT. Results The translation errors of EPID were (-1.62 ±1.58), (2.12 ±1.49) and (4.52 ±2.42)mm respectively at Lat, Vrt and Lng directions, while those of CBCT were (-1.27±1.25), (1.43±1.57) and (3.12±2.62) mm respectively. The registration errors at Lat, Vrt and Lng directions and rotation angle of lung tissue were (-1.27±1.25), (1.43±1.57), (3.12±2.62)mm and (0.5±1.6)° respectively, and those of target area were (-1.56±1.78), (1.68±2.39), (3.42±2.73)mm and (0.8±1.9)° respectively. CBCT and EPID had statistical differences (P<0.05) in setup error validation as well as setup errors at Vrt and Lng directions. There were no significant differences (P>0.05) when CBCT self-registration was involved in selecting different areas. Conclusion CBCT and EPID can both used for the setup validation of lung cancer, while the former behaved better than the latter.

GigaDB: promoting data dissemination and reproducibility.

Often papers are published where the underlying data supporting the research are not made available because of the limitations of making such large data sets publicly and permanently accessible. Even if the raw data are deposited in public archives, the essential analysis intermediaries, scripts or software are frequently not made available, meaning the science is not reproducible. The GigaScience journal is attempting to address this issue with the associated data storage and dissemination portal, the GigaScience database (GigaDB). Here we present the current version of GigaDB and reveal plans for the next generation of improvements. However, most importantly, we are soliciting responses from you, the users, to ensure that future developments are focused on the data storage and dissemination issues that still need resolving. Database URL: http://www.gigadb.org.

Disruption of the blood-brain barrier after generalized tonic-clonic seizures correlates with cerebrospinal fluid MMP-9 levels.

BACKGROUND: Increasing evidence suggests seizures cause blood-brain barrier (BBB) dysfunction including decreased seizure threshold and higher onset potential of future seizures. However, the mechanisms underlying BBB damage in seizures remains poorly understood. Evidence in human and animal models shows BBB disruption is associated with activation of matrix metalloproteinase-9 (MMP-9) after cerebral ischemia and inflammation. The objective of this study was to determine whether MMP-9 concentrations in cerebral spinal fluid (CSF) are associated with BBB disruption in patients after epileptic seizures. METHODS: Thirty-one patients with generalized tonic-clonic (GTC) seizures were included in the study: 20 had recurrent GTC seizures (RS), and 11 had a single GTC seizure (SS) episode. Twenty-five adult non-seizure patients were used as controls. CSF samples were collected by lumbar puncture within 24 h after seizure cessation (range: 3-15 h, mean 6.2 h). CSF MMP-9 levels were determined by an enzyme-linked immunosorbent assay (ELISA). MMP enzyme activity was measured by gelatin zymography. The CSF/serum albumin ratio (albumin quotient, QAlb) was used as a measure of blood-brain barrier permeability. RESULTS: We found significantly higher CSF MMP-9 concentrations in seizure patients compared with controls (P < 0.001). CSF MMP-9 levels and QAlb values were higher in RS patients compared with SS and controls. Moreover, CSF MMP-9 concentration showed strong correlation between QAlb values (r = 0.76, P < 0.0001) and between CSF leukocyte counts (r = 0.77, P < 0.0001) in patients after seizures. Gelatin zymography showed MMP-9 proteolytic activity only in GTC seizure patients. CONCLUSIONS: Our results suggest MMP-9 plays a role in BBB dysfunction, characterized by invasion of leukocytes into the CSF during seizures.