Sfrp4 is required to maintain Ctsk-lineage periosteal stem cell niche function.

We have previously reported that the cortical bone thinning seen in mice lacking the Wnt signaling antagonist Sfrp4 is due in part to impaired periosteal apposition. The periosteum contains cells which function as a reservoir of stem cells and contribute to cortical bone expansion, homeostasis, and repair. However, the local or paracrine factors that govern stem cells within the periosteal niche remain elusive. Cathepsin K (Ctsk), together with additional stem cell surface markers, marks a subset of periosteal stem cells (PSCs) which possess self-renewal ability and inducible multipotency. Sfrp4 is expressed in periosteal Ctsk-lineage cells, and Sfrp4 global deletion decreases the pool of PSCs, impairs their clonal multipotency for differentiation into osteoblasts and chondrocytes and formation of bone organoids. Bulk RNA sequencing analysis of Ctsk-lineage PSCs demonstrated that Sfrp4 deletion down-regulates signaling pathways associated with skeletal development, positive regulation of bone mineralization, and wound healing. Supporting these findings, Sfrp4 deletion hampers the periosteal response to bone injury and impairs Ctsk-lineage periosteal cell recruitment. Ctsk-lineage PSCs express the PTH receptor and PTH treatment increases the % of PSCs, a response not seen in the absence of Sfrp4. Importantly, in the absence of Sfrp4, PTH-dependent increase in cortical thickness and periosteal bone formation is markedly impaired. Thus, this study provides insights into the regulation of a specific population of periosteal cells by a secreted local factor, and shows a central role for Sfrp4 in the regulation of Ctsk-lineage periosteal stem cell differentiation and function.

Plasma cell-free RNA characteristics in COVID-19 patients.

The pathogenesis of COVID-19 is still elusive, which impedes disease progression prediction, differential diagnosis, and targeted therapy. Plasma cell-free RNAs (cfRNAs) carry unique information from human tissue and thus could point to resourceful solutions for pathogenesis and host-pathogen interactions. Here, we performed a comparative analysis of cfRNA profiles between COVID-19 patients and healthy donors using serial plasma. Analyses of the cfRNA landscape, potential gene regulatory mechanisms, dynamic changes in tRNA pools upon infection, and microbial communities were performed. A total of 380 cfRNA molecules were up-regulated in all COVID-19 patients, of which seven could serve as potential biomarkers (AUC > 0.85) with great sensitivity and specificity. Antiviral (NFKB1A, IFITM3, and IFI27) and neutrophil activation (S100A8, CD68, and CD63)-related genes exhibited decreased expression levels during treatment in COVID-19 patients, which is in accordance with the dynamically enhanced inflammatory response in COVID-19 patients. Noncoding RNAs, including some microRNAs (let 7 family) and long noncoding RNAs (GJA9-MYCBP) targeting interleukin (IL6/IL6R), were differentially expressed between COVID-19 patients and healthy donors, which accounts for the potential core mechanism of cytokine storm syndromes; the tRNA pools change significantly between the COVID-19 and healthy group, leading to the accumulation of SARS-CoV-2 biased codons, which facilitate SARS-CoV-2 replication. Finally, several pneumonia-related microorganisms were detected in the plasma of COVID-19 patients, raising the possibility of simultaneously monitoring immune response regulation and microbial communities using cfRNA analysis. This study fills the knowledge gap in the plasma cfRNA landscape of COVID-19 patients and offers insight into the potential mechanisms of cfRNAs to explain COVID-19 pathogenesis.

Single-cell sequencing identifies inflammation-promoting fibroblast-neutrophil interaction in peri-implantitis.

AIM: To reveal the cellular composition and molecular environment of the periodontal and peri-implant inflammatory infiltrates through a single-cell sequencing technique, which may explain the pathological difference between these two diseases. A special focus was placed on the phenotypes and potential roles of neutrophils and fibroblasts in peri-implant/periodontal tissue immunity. MATERIALS AND METHODS: High-throughput single-cell transcriptomic profiling of peri-implant tissues from patients with peri-implantitis as well as periodontal tissues from patients with periodontitis and healthy donors was performed. Immunofluorescence analysis was carried out to further validate the identified cell subtypes and their involvement in peri-implantitis and periodontitis. RESULTS: Based on our single-cell resolution analysis, a quantified proportional increase of neutrophil (Neu) subtypes was shown in peri-implantitis. Among these, a predominance of Neutro_CXCR2 was revealed. We also found the involvement of inflammation-promoting fibroblasts as well as a predominance of CXCL8+ fibroblast-CXCR2+ neutrophil interaction in peri-implantitis. CONCLUSIONS: Our study indicated that the predominance of CXCL8+ fibroblast-CXCR2+ neutrophil interaction might underline the enhanced host response in peri-implantitis compared with periodontitis. This information offers a molecular basis by which fibroblast and neutrophil subtypes might be diagnostically and therapeutically targeted in peri-implantitis.

Potential of combined reactor and static composting applications for the removal of heavy metals and antibiotic resistance genes from chicken manure.

Chicken manure (CM) can pose a serious threat to environmental and human health, and need to be managed properly. The compost can effectively treat CM. However, there is limited research on the heavy metals and antibiotic resistance genes (ARGs) during compost CM. In this study, the combined application of reactor and static composting (RSC) was used to produce organic fertilizer of CM (OCM), and heavy metals, ARGs and bacterial community structure was investigated. The results show that RSC could be used to produce OCM, and OCM meet the National organic fertilizer standard (NY/T525-2021). Compared to the initial CM, DTPA-Cu, DTPA-Zn, DTPA-Pb, DTPA-Cr, DTPA-Ni and DTPA-As in OCM decreased by 40.83%, 23.73%, 34.27%, 38.62%, 16.26%, and 43.35%, respectively. RSC decreased the relative abundance of ARGs in CM by 84.06%, while the relative abundance of sul1 and ermC increased. In addition, the relative abundance and diversity of ARGs were mainly influenced by the bacterial community, with Actinobacteria, Firmicutes, and Proteobacteria becoming the dominant phyla during composting, and probably being the main carriers and dispersers of most of the ARGs. Network analyses confirmed that Gracilibacillus, Lactobacillus, Nocardiopsis, Mesorhizobium and Salinicoccus were the main potential hosts of ARGs, with the main potential hosts of sul1 and ermC being Mesorhizobium and Salinicoccus. The passivation and physicochemical properties of heavy metals contribute to the removal of ARGs, with sul1 and ermC being affected by the toal heavy metals. Application of RSC allows CM to produce mature, safe organic fertilizer after 32 d and reduces the risk of rebound from ARGs, but the issues of sul1 and ermC gene removal cannot be ignored.

Impact of periodontitis on type 2 diabetes: a bioinformatic analysis.

BACKGROUND: Periodontitis is strongly associated with type 2 diabetes (T2D) that results in serious complications and mortality. However, the pathogenic role of periodontitis in the development of T2D and the underlain mechanism have not been fully elucidated. METHODS: A Mendelian randomization (MR) was performed to estimate the causality between two diseases. Bioinformatics tools, including gene ontology and pathway enrichment analyses, were employed to analyze the common differentially expressed genes (DEGs) in periodontitis and T2D. MR and colocalization analyses were then utilized to investigate the causal associations between potential pathogenic gene expression and the risk of T2D. Single cell-type expression analysis was further performed to detect the cellular localization of these genes. RESULTS: Genetically predicted periodontitis was associated with a higher risk of T2D (OR, 1.469; 95% CI, 1.117-1.930; P = 0.006) and insulin resistance (OR 1.034; 95%CI 1.001-1.068; P = 0.041). 79 common DEGs associated with periodontitis and T2D were then identified and demonstrated enrichment mainly in CXC receptor chemokine receptor binding and interleutin-17 signaling pathway. The integration of GWAS with the expression quantitative trait locis of these genes from the peripheral blood genetically prioritized 6 candidate genes, including 2 risk genes (RAP2A, MCUR1) and 4 protective genes (WNK1, NFIX, FOS, PANX1) in periodontitis-related T2D. Enriched in natural killer cells, RAP2A (OR 4.909; 95% CI 1.849-13.039; P = 0.001) demonstrated high risk influence on T2D, and exhibited strong genetic evidence of colocalization (coloc.abf-PPH4 = 0.632). CONCLUSIONS: This study used a multi-omics integration method to explore causality between periodontitis and T2D, and revealed molecular mechanisms using bioinformatics tools. Periodontitis was associated with a higher risk of T2D. MCUR1, RAP2A, FOS, PANX1, NFIX and WNK1 may play important roles in the pathogenesis of periodontitis-related T2D, shedding light on the development of potential drug targets.

Aberrant m5C hypermethylation mediates intrinsic resistance to gefitinib through NSUN2/YBX1/QSOX1 axis in EGFR-mutant non-small-cell lung cancer.

BACKGROUND: RNA 5-methylcytosine (m5C) modification plays critical roles in the pathogenesis of various tumors. However, the function and molecular mechanism of RNA m5C modification in tumor drug resistance remain unclear. METHODS: The correlation between RNA m5C methylation, m5C writer NOP2/Sun RNA methyltransferase family member 2 (NSUN2) and EGFR-TKIs resistance was determined in non-small-cell lung cancer (NSCLC) cell lines and patient samples. The effects of NSUN2 on EGFR-TKIs resistance were investigated by gain- and loss-of-function assays in vitro and in vivo. RNA-sequencing (RNA-seq), RNA bisulfite sequencing (RNA-BisSeq) and m5C methylated RNA immunoprecipitation-qPCR (MeRIP-qPCR) were performed to identify the target gene of NSUN2 involved in EGFR-TKIs resistance. Furthermore, the regulatory mechanism of NSUN2 modulating the target gene expression was investigated by functional rescue and puromycin incorporation assays. RESULTS: RNA m5C hypermethylation and NSUN2 were significantly correlated with intrinsic resistance to EGFR-TKIs. Overexpression of NSUN2 resulted in gefitinib resistance and tumor recurrence, while genetic inhibition of NSUN2 led to tumor regression and overcame intrinsic resistance to gefitinib in vitro and in vivo. Integrated RNA-seq and m5C-BisSeq analyses identified quiescin sulfhydryl oxidase 1 (QSOX1) as a potential target of aberrant m5C modification. NSUN2 methylated QSOX1 coding sequence region, leading to enhanced QSOX1 translation through m5C reader Y-box binding protein 1 (YBX1). CONCLUSIONS: Our study reveals a critical function of aberrant RNA m5C modification via the NSUN2-YBX1-QSOX1 axis in mediating intrinsic resistance to gefitinib in EGFR-mutant NSCLC.

Pontibacterium sinense sp. nov., a nitrate-reducing and thiosulphate-oxidizing bacterium, isolated from coastal sediment.

A novel bacterial strain, N1Y112T, was isolated from coastal sediment collected in Weihai, PR China. This Gram-stain-negative, facultatively anaerobic, motile rod-shaped bacterium exhibited the ability to oxidize thiosulphate to sulphate and reduce nitrate to ammonia through its Sox system and nitrate reduction pathway, respectively. The strain grew at 20-35 °C (optimum, 28 °C), pH 6.0-10.0 (optimum, pH 7.5) and in the presence of 1.0-5.0 % (w/v) NaCl (optimum, 3.0 %). Major fatty acids present in the strain included summed feature 8 (comprising C18 : 1 ω7c and/or C18 : 1 ω6c), summed feature 3 (comprising C16 : 1 ω7c and/or C16 : 1 ω6c) and C16 : 0. Its polar lipid profile consisted of one phosphatidylethanolamine, two unknown aminolipids, one aminophosphoglycolipid, one diphosphatidylglycerol, one phosphatidylglycerol, two unknown phospholipids and two unknown lipids. Strain N1Y112T contained ubiquinone-7 and ubiquinone-8 as isoprenoid quinones, with a genomic G+C content of 50.6 mol%. Based on phylogenetic analysis, strain N1Y112T clustered with Pontibacterium granulatum JCM 30316T being its closest relative at 97.1 % 16S rRNA gene sequence similarity. The average nucleotide identity and digital DNA-DNA hybridization values were 77.1 and 20.7 %, respectively, which suggest significant differences between genomes of N1Y112T and P. granulatum JCM 30316T. Based on the findings from its phenotypic, genotypic and phylogenetic analyses, N1Y112T is considered to represent a novel species of the genus Pontibacterium, for which the name Pontibacterium sinense sp. nov. is proposed. The type strain is N1Y112T (=KCTC 72927T=MCCC 1H00429T).

Derivation and validation of a prediction model for patients with lung nodules malignancy regardless of mediastinal/hilar lymphadenopathy.

BACKGROUND: Clinical prediction models to classify lung nodules often exclude patients with mediastinal/hilar lymphadenopathy, although the presence of mediastinal/hilar lymphadenopathy does not always indicate malignancy. Herein, we developed and validated a multimodal prediction model for lung nodules in which patients with mediastinal/hilar lymphadenopathy were included. METHODS: A single-center retrospective study was conducted. We developed and validated a logistic regression model including patients with mediastinal/hilar lymphadenopathy. Discrimination of the model was assessed by area under the operating curve. Goodness of fit test was performed via the Hosmer-Lemeshow test, and a nomogram of the logistic regression model was drawn. RESULTS: There were 311 cases included in the final analysis. A logistic regression model was developed and validated. There were nine independent variables included in the model. The aera under the curve (AUC) of the validation set was 0.91 (95% confidence interval [CI]: 0.85-0.98). In the validation set with mediastinal/hilar lymphadenopathy, the AUC was 0.95 (95% CI: 0.90-0.99). The goodness-of-fit test was 0.22. CONCLUSIONS: We developed and validated a multimodal risk prediction model for lung nodules with excellent discrimination and calibration, regardless of mediastinal/hilar lymphadenopathy. This broadens the application of lung nodule prediction models. Furthermore, mediastinal/hilar lymphadenopathy added value for predicting lung nodule malignancy in clinical practice.

Sfrp4 and the Biology of Cortical Bone.

PURPOSE OF REVIEW: Periosteal apposition and endosteal remodeling regulate cortical bone expansion and thickness, both critical determinants of bone strength. Yet, the cellular characteristics and local or paracrine factors that regulate the periosteum and endosteum remain largely elusive. Here we discuss novel insights in cortical bone growth, expansion, and homeostasis, provided by the study of Secreted Frizzled Receptor Protein 4 (Sfrp4), a decoy receptor for Wnt ligands. RECENT FINDINGS: SFRP4 loss-of function mutations cause Pyle disease, a rare skeletal disorder characterized by cortical bone thinning and increased fragility fractures despite increased trabecular bone density. On the endosteal surface, Sfrp4-mediated repression of non-canonical Wnt signaling regulates endosteal resorption. On the periosteum, Sfrp4 identifies as a critical functional mediator of periosteal stem cell/progenitor expansion and differentiation. Analysis of signaling pathways regulating skeletal stem cells/progenitors provides an opportunity to advance our understanding of the mechanisms involved in cortical bone biology.

Favorable outcome in PLA2R positive HBV-associated membranous nephropathy.

INTRODUCTION: Over half of the patients with hepatitis B virus associated membranous nephropathy (HBV-MN) were found to be phospholipase A2 receptor (PLA2R) positive. Whether MN is really secondary to hepatitis B or just coincidence of hepatitis and PLA2R positive idiopathic MN (IMN) remains controversial. METHODS: We retrospectively studied seven PLA2R positive HBV-MN patients with complete data in Huashan Hospital from 2009 to 2016 and compared them with PLA2R positive idiopathic MN patients. RESULTS: Proteinuria and renal function of these 7 HBV-MN patients were similar to that of IMN patients. However, 5 of them were female and half showed hypocomplementemia, while in IMN group only 32.4% were female and 20% had hypocomplementemia, and the level of hematuria was 94.5/µL in HBV-MN patients and 64.9 /µL in IMN patients, though there was no statistically significant difference. Renal biopsies revealed significantly increased mesangial eletron-deposits in HBV-MN patients. All 7 patients received antiviral therapy, and one patient received immunosuppresants due to severe nephrotic syndrome with acute myocardial infarction and elevated serum creatinine. Compared with IMN group, the prevalence of remission without immunosuppressive therapy of HBV-MN patients was higher (85.7% vs. 43.7%), while the percentage of patients receiving immunosuppresants was lower (14.3% vs. 47.9%) (P=0.048). CONCLUSION: Compared with IMN patients, PLA2R positive HBV-MN patients had a more favorable prognosis after antiviral therapy, indicating a secondary form of MN. For these patients, antiviral treatment is recommended and long observation time should be provided before use of immunosuppressive treatment.

Sfrp4 repression of the Ror2/Jnk cascade in osteoclasts protects cortical bone from excessive endosteal resorption.

Loss-of-function mutations in the Wnt inhibitor secreted frizzled receptor protein 4 (SFRP4) cause Pyle's disease (OMIM 265900), a rare skeletal disorder characterized by wide metaphyses, significant thinning of cortical bone, and fragility fractures. In mice, we have shown that the cortical thinning seen in the absence of Sfrp4 is associated with decreased periosteal and endosteal bone formation and increased endocortical resorption. While the increase in Rankl/Opg in cortical bone of mice lacking Sfrp4 suggests an osteoblast-dependent effect on endocortical osteoclast (OC) activity, whether Sfrp4 can cell-autonomously affect OCs is not known. We found that Sfrp4 is expressed during bone marrow macrophage OC differentiation and that Sfrp4 significantly suppresses the ability of early and late OC precursors to respond to Rankl-induced OC differentiation. Sfrp4 deletion in OCs resulted in activation of canonical Wnt/ß-catenin and noncanonical Wnt/Ror2/Jnk signaling cascades. However, while inhibition of canonical Wnt/ß-catenin signaling did not alter the effect of Sfrp4 on OCgenesis, blocking the noncanonical Wnt/Ror2/Jnk cascade markedly suppressed its regulation of OC differentiation in vitro. Importantly, we report that deletion of Ror2 exclusively in OCs (CtskCreRor2fl/fl ) in Sfrp4 null mice significantly reversed the increased number of endosteal OCs seen in these mice and reduced their cortical thinning. Altogether, these data show autocrine and paracrine effects of Sfrp4 in regulating OCgenesis and demonstrate that the increase in endosteal OCs seen in Sfrp4-/- mice is a consequence of noncanonical Wnt/Ror2/Jnk signaling activation in OCs overriding the negative effect that activation of canonical Wnt/ß-catenin signaling has on OCgenesis.

Three-dimensional magnetic resonance imaging assessment of levator ani in women progressing from full-term pregnancy to 10 months postpartum.

AIM: To identify the anatomical morphology of levator ani (LA) in primigravidae at term pregnancy and its natural process of changing after delivery. METHODS: Forty-one primigravidae (vaginal delivery: 29 women, cesarean delivery in the first stage of labor: 12 women) underwent magnetic resonance imaging (MRI) at full-term pregnancy, 6 weeks and 10 months postpartum. Three-dimensional (3-D) model of LA created from MRI data using Mimics v.21.0 software and source images were assessed to determine the morphology. LA volume (LVOL) was calculated and used as indicator of muscle atrophy. RESULTS: Decrease of levator hiatus length (LH-L) was shown in both groups since 6 weeks postpartum. In the vaginal delivery group, the differences in LVOL between time points were significant (p < 0.05), showing a persistent decreasing tendency. Puborectalis attachment width (PAW) on the left was the smallest at 6 weeks postpartum (p < 0.05). LA avulsion and significant 2-D morphological change after delivery were only observed in this group (p < 0.05); In the cesarean section group, smaller LVOL was found at 6 weeks postpartum comparing with full-term pregnancy (p < 0.05); Larger levator-symphysis gap (LSG) and levator hiatus width (LH-W), smaller PAW were observed in vaginal delivery group comparing with cesarean section group at 6 weeks postpartum (p < 0.05), but none of the values exhibited between-group differences (p > 0.05) at 10 months postpartum. No other comparisons were considered significant (p >0.05). CONCLUSIONS: Vaginal delivery, or even active labor itself may both lead to LA atrophy. And the morphology of LA is basically similar in different delivery modes at 10 months postpartum once the onset of labor has occurred, even though it changes more complicatedly after vaginal delivery.

Alternation of nasopharyngeal microbiota in healthy youth is associated with environmental factors: implication for respiratory diseases.

The nasopharynx is a key niche of the upper respiratory tract which contains many commensal bacteria and potential pathogens. Dysbiosis of the nasopharyngeal (NP) microbiota is associated with a variety of respiratory diseases. Little is known about NP flora in healthy youth, nor about its relationship with environmental factors. We characterized NP microbiota using the 16S rRNA gene sequencing method, and compared microbial composition from subjects sampled in Spring and Fall when exposed to different environmental factors. Results showed that beta diversity was significantly different. Phyla Acidobacteria, Gemmatimonadetes, and genus Symbiobacterium were positively associated with PM2.5. Genera Streptococcus, Prevotella, and [Prevotella] were positively correlated with temperature (T). Ozone (O3) was associated with these floras for exposure that occurred 30 days prior to collection. These preliminary data suggest that the change in environmental factors between spring and fall can influence the composition of the NP microbiota, characterized by a significant correlation to specific taxa. These changes in NP microbiota might be a potential risk factor for respiratory disease.

LncRNA RP11-84E24.3 drives tumorigenesis and epithelial-to-mesenchymal transition of glioma cells by promoting TFAP2C-mediated activation of SNAI1.

PURPOSE: Long noncoding RNAs (LncRNAs) are essential epigenetic regulators with critical roles in tumor initiation and malignant progression; however, the mechanism by which aberrantly expressed lncRNA RP11-84E24.3 regulates the pathogenesis of glioma is not fully understood. Here, we investigate the function of lncRNA RP11-84E24.3 in glioma onset and progression as well as identify a molecular pathway regulated by this lncRNA. METHODS: Differentially expressed lncRNAs related to glioma were identified. The aberrant expression of lncRNA RP11-84E24.3 was verified in samples from patients with glioma as well as glioma cell lines. The role of lncRNA RP11-8424.3 in proliferation, apoptosis, migration, and invasion was assessed using gain- and loss-of function approaches, EdU incorporation, flow cytometry, wound healing and Transwell invasion assays. Western blot analysis was utilized to examine the expression of proteins associated with epithelial-to-mesenchymal transition (EMT). The interaction between lncRNA RP11-84E24.3, TFAP2C and SNAI1 was confirmed using RNA pull-down, ChIP and luciferase reporter assays. RESULTS: LncRNA RP11-84E24.3 was up-regulated in both glioma tissues and cell lines. LncRNA RP11-84E24.3 overexpression enhanced the proliferation, migration and invasion of glioma cells while reducing apoptosis. This was associated with a decrease in E-cadherin expression and an increase in N-cadherin and Vimentin expression. LncRNA RP11-84E24.3 directly targeted TFAP2C protein, resulting in increased SNAI1 expression. Knockdown of TFAP2C or SNAI1 reversed the effects of lncRNA RP11-84E24.3 overexpression, while silencing lncRNA RP11-84E24.3 inhibited tumor formation of glioma cells in vivo. CONCLUSIONS: LncRNA RP11-84E24.3 increased SNAI1 expression by forming a complex with TFAP2C protein, promoting EMT in glioma cells and tumor formation.

Remodeling immune microenvironment in periodontitis using resveratrol liposomes as an antibiotic-free therapeutic strategy.

BACKGROUND: Periodontitis is a complicated inflammatory disease that damages the tooth-supporting tissues, with limited pharmacotherapy available. Macrophage-targeting therapy is promising for inflammatory diseases. Resveratrol (RSV), a nonflavonoid polyphenol, is known for its anti-inflammatory and immunomodulatory effects. However, its medical application is limited by its poor stability and water-solubility, as well as its low bioavailability. RESULT: A therapeutic resveratrol-loaded liposomal system (Lipo-RSV) was developed to treat periodontitis. The physical properties of Lipo-RSV and its ability to regulate macrophages were investigated. The results showed that Lipo-RSV had good biocompatibility and could re-educate the inflammatory macrophages from M1- to M2-like phenotype through activating p-STAT3 and downregulating p-STAT1. Besides, the Lipo-RSV could scavenge ROS and inhibit the NF-κB signal and inflammasomes, thereby reducing the pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α. CONCLUSION: These results revealed that Lipo-RSV could be a potential therapeutic system for the antibiotic-free treatment for periodontal diseases.

Geniposide suppresses liver injury in a mouse model of DDC-induced sclerosing cholangitis.

Sclerosing cholangitis, characterized by biliary inflammation, fibrosis, and stricturing, remains one of the most challenging conditions of clinical hepatology. Geniposide (GE) has anti-inflammatory, hepatoprotective, and cholagogic effects. Whether GE provides inhibition on the development of sclerosing cholangitis is unknown. Here, we investigated the role of GE in a mouse model in which mice were fed with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) for 4 weeks to induce sclerosing cholangitis. The results demonstrated that the increased hepatic gene expressions of pro-inflammatory (IL-6, VCAM-1, MCP-1, and F4/80) and profibrogenic markers (Col1α1, Col1α2, TGF-ß, and α-SMA) in DDC feeding mice were reversed after treatment with GE. GE also suppressed expressions of CK19 and Ki67 in DDC-fed mice, suggesting that GE could ameliorate DDC-induced hepatocytes and cholangiocytes proliferation. In addition, GE significantly increased bile acids (BAs) secretion in bile, which correlated with induced expressions of hepatic FXR, BAs secretion transporters (BSEP, MRP2, MDR1, and MDR2), and reduced CYP7A1 mRNA expression. Furthermore, higher expressions of ileal FXR-FGF15 signaling and reduced ASBT were also observed after GE treatment. Taken together, these data showed that GE could modulate inflammation, fibrosis, and BAs homeostasis in DDC-fed mice, which lead to efficiently delay the progression of sclerosing cholangitis.

Digital anatomic study of the ureter relative to bifurcation of the common iliac artery in females.

INTRODUCTION: Laparoscopic salpingo-oophorectomy and pelvic lymphadenectomy place the ureter at risk. Although traditional anatomic studies indicate that ureters generally cross over the common iliac artery in the pelvic inlet, the view is often different during surgery. Hence, digital three-dimensional models have been utilized to solve this conundrum. Our study aimed to evaluate the anatomic relation between the iliac artery and the ureter in the pelvic inlet. MATERIAL AND METHODS: A medical image processing system processed data collected from 129 female patients, and digital 3D models of the iliac artery and ureter were used to study their anatomic relation. Left- and right-side data were compared using Pearson's χ2 analysis. RESULTS: Two different anatomic relations were found immediately posterior to the ureter: Common iliac arteries were present in 33.2% and external iliac arteries in 76.8%. The mean distances from the point at which the ureter crossed over the iliac artery until the bifurcation of the artery was 8.8 ± 12.2 mm in the left pelvis and 12.4 ± 10.8 mm in the right pelvis - different from that of the traditional anatomic study. CONCLUSION: In the future, these models and digital anatomical data could help avoid surgical complications.

Genome-wide data mining to construct a competing endogenous RNA network and reveal the pivotal therapeutic targets of Parkinson's disease.

Parkinson's disease (PD) is one of the most common neurodegenerative movement disorders, for which there has been no effective treatments. To clarify the pathogenesis of PD, we constructed a competing endogenous RNA (ceRNA) network based on the genome-wide RNA sequencing data. It was found that 92 RNAs were differentially expressed, including 50 mRNAs, 25 miRNAs and 17 lncRNAs, based on which a ceRNA network was constructed and evaluated from 4 aspects of number of nodes, topological coefficients, closeness centrality and betweenness centrality. The functional annotation and enrichment analysis suggested that 6 functional modules, particularly the peripheral nervous system development and toxin metabolic process, dominated the development of PD. To validate the assumption, the gene set enrichment analysis (GSEA) was conducted basing on the genome-wide RNAs regardless whether they were differentially expressed or not. Consistently, the results revealed that dysregulation of MAG, HOXB3, MYRF and PLP1 led to metabolic disorders of sphingolipid and glutathione, which contributed to the pathogenesis of PD. Also, in-depth mining of previous literature confirmed a pivotal role of these dysregulated RNAs, which had been indicated to be potential diagnostic and therapeutic biomarkers of PD. Overall, we constructed a ceRNA network based on the dysregulated mRNAs, lncRNAs and miRNAs in PD, and the aberrant expression of MAG, HOXB3, MYRF and PLP1 caused metabolism disorder of sphingolipid and glutathione, and these genes are of great significance for the diagnosis and treatment of PD.

Bacterial composition and community structure of the oropharynx of adults with asthma are associated with environmental factors.

The development and exacerbation of asthma are mainly attributed to inflammatory reactions caused by allergens. However, less is known about the development of asthma caused by microbial disorders in the oropharynx and induced by environmental factors. Here, the metagenome of the oropharyngeal microbiome of adults with asthma was analysed to identify their association with air pollutants. Oropharyngeal swabs from patients with asthma were collected in two winters (W1 and W2) with different environmental factor exposures. The bacterial composition and community structure of the oropharynx were analysed through high-throughput sequencing. After analysis, the α-diversity and ß-diversity exhibited significant differences between the two groups. LEfSe analysis detected 8 significantly different phyla and 11 significantly different genera between the W1 and W2 groups. Multiple linear regression analyses found that the asthma status might contribute to the alteration of microbial composition. Redundancy analysis showed that NO2 was the only environmental factor that significantly affected the microbial community structure of the oropharynx. The different genera associated with NO2 were Rothia, Actinomyces, Fusobacterium and Leptotrichia. The altered taxa related to PM2.5 were Cupriavidus and Acinetobacter. Actinobacillus and Prevotella showed a highly positive correlation with O3. Moreover, network analysis was carried out to explore the co-occurrence relationships of the main genera, and PICRUSt was conducted to predict bacterial functions. This study showed that environmental factors might cause alteration in the oropharyngeal flora, which might be a potential risk factor of asthma.

Reconstruction of three-dimensional vascular models for lymphadenectomy before surgery.

Introduction: A three-dimensional (3D) model of the pelvic vessels was reconstructed before surgery to aid in the understanding of the individual anatomy and help guide lymphadenectomy performance.Material and methods: Thirty patients with early-stage cervical cancer who were scheduled for lymphadenectomy at Nanfang Hospital, Southern Medical University from January 2017 to June 2017 were included. Three-dimensional models of the pelvic vessels were obtained.Results: All 3D models of the 30 patients were reconstructed successfully and were consistent with the operative findings.The most common structural types posterior to the common iliac artery (CIA) and CIA bifurcation (CIAB) were non-vessel structures (23/30 patients) and the common iliac vein (CIV) (27/30); these were observed separately on the left pelvic vein. The confluence of common iliac vein (CCIV) (29/30) and CIV (20/30) were most commonly observed posterior to the CIA and CIAB; these were observed separately on the right pelvic vein. Venous abnormalities were identified in 15 patients. There were variants in venous confluence shown to be homolateral to the CIV (2/15) and contralateral to the CIV (2/15) and CCIV (4/15).Conclusions: Three-dimensional models of the pelvic vessels can provide information on individual anatomy features that can help guide lymphadenectomy performance.