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Epstein-Barr virus (EBV) infects over 95% of the global population and is strongly associated with various autoimmune diseases. Anti-nuclear antibodies (ANA) serve as valuable laboratory biomarkers for screening and supporting the diagnosis of various autoimmune diseases. The aim of this study was to assess the prevalence of EBV infection and its association with ANA. This retrospective study employed standard indirect immunofluorescence assay to determine ANA levels, EBV-specific immunofluorescence assay, or plasma EBV-DNA testing. Demographic data including gender and age were collected to observe variations in EBV infection status and ANA positivity rates among different populations. Incorporating 6492 hospitalized patients who underwent ANA antibody spectrum testing, it was observed that serum positivity rates gradually increased with age. The overall serum positivity rate of ANA in females (25.14%) was significantly higher than that in males (13.76%). Among hospitalized patients undergoing EBV-DNA testing, adults aged 21 to 40 years were least affected by EBV, with a positivity rate of 11.96%; however, as age increased, the positivity rate gradually increased. Among the 5225 patients undergoing EBV antibody spectrum testing, ANA-positive patients exhibited significantly higher serum positivity rates for Epstein-Barr nuclear antigen 1 immunoglobulin G, Epstein-Barr virus early antigen immunoglobulin G, Epstein-Barr virus early antigen immunoglobulin A, and Epstein-Barr virus viral capsid antigen immunoglobulin A antibodies compared to ANA-negative patients (Pâ <â .001; Pâ <â .001; Pâ =â .013; Pâ <â .001). The EBV-DNA positivity rate in ANA-positive patients was also significantly higher than in ANA-negative patients, yielding the same conclusion (Pâ =â .012). The positivity rates of ANA antibodies in patients with past EBV infection and reactivation were significantly higher than those in uninfected patients (Pâ <â .001; Pâ =â .006). The positivity rate of ANA antibodies in reactivated patients was significantly higher than that in primary infected patients and those with past infections (Pâ <â .001; Pâ <â .001). Among ANA-positive patients, the positivity rates of EBV antibody spectrum and EBV-DNA were higher compared to ANA-negative patients. The positivity rates of ANA in patients with past EBV infection and reactivation were higher than those in uninfected patients.
Subject(s)
Antibodies, Antinuclear , Epstein-Barr Virus Infections , Herpesvirus 4, Human , Humans , Epstein-Barr Virus Infections/epidemiology , Epstein-Barr Virus Infections/blood , Epstein-Barr Virus Infections/immunology , Epstein-Barr Virus Infections/diagnosis , Female , Male , Antibodies, Antinuclear/blood , China/epidemiology , Adult , Cross-Sectional Studies , Middle Aged , Retrospective Studies , Young Adult , Adolescent , Child , Herpesvirus 4, Human/immunology , Aged , DNA, Viral/blood , Child, Preschool , Antibodies, Viral/blood , Infant , PrevalenceABSTRACT
As a promising gene therapy strategy, controllable small molecule-mRNA covalent modification in tumor cells could be initiated by singlet oxygen (1O2) to complete the modification process. However, in vivo generation of 1O2 is usually dependent on excitation of external light, and the limited light penetration of tissues greatly interferes the development of deep tumor phototherapy. Here, we constructed a tumor-targeting nano-micelle for the spontaneous intracellular generation of 1O2 without the need for external light, and inducing a high level of covalent modification of mRNA in tumor cells. Luminal and Ce6 were chemically bonded to produce 1O2 by chemiluminescence resonance energy transfer (CRET) triggered by high levels of hydrogen peroxide (H2O2) in the tumor microenvironment. The sufficient 1O2 oxidized the loaded furan to highly reactive dicarbonyl moiety, which underwent cycloaddition reaction with adenine (A), cytosine (C) or guanine (G) on the mRNA for interfering with the tumor cell protein expression, thereby inhibiting tumor progression. In vitro and in vivo experiments demonstrated that this self-initiated gene therapy nano-micelle could induce covalent modification of mRNA by 1O2 without external light, and the process could be monitored in real time by fluorescence imaging, which provided an effective strategy for RNA-based tumor gene therapy.
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BACKGROUND Odontogenic keratocyst (OKC) is a common odontogenic cyst, and it occurs more frequently in the mandible, with the posterior region of the dental arch, the angle, or the ramus being the most commonly affected sites. Odontogenic keratocyst occurring within the maxillary sinus is extremely rare, accounting for only about 1% of cases. CASE REPORT A 20-year-old female patient without any clinical symptoms underwent an oral examination, during which a dense dental shadow was identified within the maxillary sinus, surrounded by a low-density shadow. Physical examination revealed absence of the left maxillary third molar, with intact mucosa. The patient reported no history of tooth extraction. X-ray and cone-beam computed tomography revealed a high-density image within the left maxillary sinus, resembling a tooth and surrounded by a soft-tissue shadow, which exhibited a greater density in comparison to conventional odontogenic cysts. The initial diagnosis was odontogenic keratocyst in the maxillary sinus with an ectopic maxillary third molar. Surgical enucleation of the cyst and extraction of the impacted tooth were carried out utilizing the Caldwell-Luc approach. Histopathological analysis confirmed the presence of OKC. No significant recurrence was noted during the 6 months of follow-up. CONCLUSIONS Odontogenic keratocysts in the maxillary sinus with ectopic third molar are rare and may not have any symptoms in the early stage. Surgery can be performed using the Caroler-Luke approach to achieve ideal treatment results. In view of the high recurrence rate of OKC, close follow-up should be conducted after surgery.
Subject(s)
Maxillary Sinus , Molar, Third , Odontogenic Cysts , Humans , Odontogenic Cysts/surgery , Odontogenic Cysts/diagnostic imaging , Female , Molar, Third/surgery , Maxillary Sinus/diagnostic imaging , Maxillary Sinus/pathology , Young Adult , Cone-Beam Computed Tomography , Paranasal Sinus Diseases/surgery , Paranasal Sinus Diseases/diagnostic imaging , Tooth ExtractionABSTRACT
BACKGROUND: The aqueous humor, a transparent fluid secreted by the ciliary body, supports the lens of the eyeball. In this study, we analyzed the cytokine and chemokine profiles within the aqueous humor of the contralateral eye post-implantation of an implantable collamer lens (ICL) to evaluate potential subclinical inflammation in the second eye subsequent to ICL implantation in the first eye. METHODS: Aqueous humor samples were procured from both eyes of 40 patients (totaling 80 eyes) prior to bilateral ICL insertion. Subsequently, a comprehensive statistical analysis was conducted using the Luminex assay to quantify 30 different cytokines in these samples. RESULTS: Compared to the first eye, the aqueous humor of the second eye demonstrated decreased concentrations of IFN-γ (P = 0.038), IL-13 (P = 0.027), IL-17/IL-17 A (P = 0.012), and IL-4 (P = 0.025). No significant differences were observed in other cytokine levels between the two groups. Patients were then categorized based on the postoperative rise in intraocular pressure (IOP) in the first eye. The group with elevated IOP displayed elevated levels of EGF in the aqueous humor of the first eye (P = 0.013) and higher levels of PDGF-AB/BB in the aqueous humor of the second eye (P = 0.032) compared to the group with normal IOP. Within the elevated IOP group, the levels of EGF (P = 0.013) and IL-17/IL-17 A (P = 0.016) in the aqueous humor were lower in the second eye than in the first eye. In the normal IOP group, cytokine levels did not differ notably between eyes. CONCLUSION: Following sequential ICL implantation, it appears that a protective response may be activated to mitigate subclinical inflammation in the second eye induced by the initial implantation in the first eye. Additionally, the increase in IOP subsequent to surgery in the first eye may correlate with the presence of inflammatory mediators in the aqueous humor.
Subject(s)
Aqueous Humor , Cytokines , Myopia , Humans , Aqueous Humor/metabolism , Male , Female , Myopia/surgery , Myopia/metabolism , Adult , Cytokines/metabolism , Lens Implantation, Intraocular , Inflammation , Middle Aged , Intraocular Pressure , Young AdultABSTRACT
A vitamin D receptor (VDR) deficiency leads to the dysbiosis of intestinal bacteria and is associated with various diseases, including cancer, infections, and inflammatory bowel disease. However, the impact of a VDR deficiency on fungi and archaea is unknown. We conditionally deleted the VDR in Paneth cells (VDRΔPC), intestinal epithelial cells (VDRΔIEC), or myeloid cells (VDRΔLyz) in mice and collected feces for shotgun metagenomic sequencing and untargeted metabolomics. We found that fungi were significantly altered in each knockout (KO) group compared to the VDRLoxp control. The VDRΔLyz mice had the most altered fungi species (three depleted and seven enriched), followed by the VDRΔPC mice (six depleted and two enriched), and the VDRΔIEC mice (one depleted and one enriched). The methanogen Methanofollis liminatans was enriched in the VDRΔPC and VDRΔLyz mice and two further archaeal species (Thermococcus piezophilus and Sulfolobus acidocaldarius) were enriched in the VDRΔLyz mice compared to the Loxp group. Significant correlations existed among altered fungi, archaea, bacteria, and viruses in the KO mice. Functional metagenomics showed changes in several biologic functions, including decreased sulfate reduction and increased biosynthesis of cobalamin (vitamin B12) in VDRΔLyz mice relative to VDRLoxp mice. Fecal metabolites were analyzed to examine the involvement of sulfate reduction and other pathways. In conclusion, a VDR deficiency caused the formation of altered fungi and archaea in a tissue- and sex-dependent manner. These results provide a foundation about the impact of a host factor (e.g., VDR deficiency) on fungi and archaea. It opens the door for further studies to determine how mycobiome and cross-kingdom interactions in the microbiome community and metabolites contribute to the risk of certain diseases.
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BACKGROUND: With more pregnant women undergoing cesarean section, the number of women with scarring in the uterus undergoing uterine magnetic resonance (MR) examination in the second and third trimesters following a subsequent pregnancy, has increased. OBJECTIVE: To investigate features of MR signals in retroplacental basal decidual space. METHODS: The MR imaging data of patients with clinically and pathologically confirmed placenta implantation and complete placental abruption were retrospectively analyzed. RESULTS: Patients with high-intensity signals in T2-weighted images (T2WI) of the retroplacental basal decidual space did not suffer placenta implantation after delivery, while high-intensity signals in T2WI of the retroplacental basal decidual space was not observed in patients with different degrees of placenta implantation. CONCLUSION: As the retroplacental basal decidual space is the barrier between the placenta and myometrium, high-intensity signals in T2WI can improve the confidence of MR exclusion diagnostics of placenta implantation, and can be used as exclusion criteria for MR diagnosis of placenta implantation.
Subject(s)
Cesarean Section , Placenta , Pregnancy , Female , Humans , Placenta/diagnostic imaging , Retrospective Studies , Magnetic Resonance Imaging/methods , Magnetic Resonance SpectroscopyABSTRACT
OBJECTIVE@#To assess the effectiveness and feasibility of carrier detection for Spinal muscular atrophy (SMA) by using digital PCR assay.@*METHODS@#Peripheral blood samples were collected from 214 pregnant women who were routinely screened for SMA carriers, of which 204 were randomly selected samples and 10 were samples with known copy numbers of SMN1 exons 7 and 8. Samples with known copy numbers of SMN1 exons 7 and 8 were randomly mixed into the experiment to validate the performance of the digital PCR assay.@*RESULTS@#The copy numbers of SMN1 exons 7 and 8 and SMN2 exons 7 and 8 in peripheral blood samples were detected by digital PCR assay. The results of SMN1 exons 7 and 8 were compared with those of the quantitative PCR method to assess the reliability and clinical performance of the digital PCR assay. Among the 204 random samples, digital PCR has detected five samples with simultaneous heterozygous deletion of SMN1 exons 7 and 8, three samples with heterozygous deletion of SMN1 exon 8 only, and 196 samples with no deletion of SMN1 exons 7 and 8. Ten samples with known SMN1 exons 7 and 8 copy numbers were detected with the expected values. The digital PCR test results were fully consistent with that of the quantitative PCR.@*CONCLUSION@#The results of digital PCR for the detection of copy number variation of SMN1 exons 7 and 8 were consistent with qPCR. Digital PCR assay was able to clearly distinguish the copy number of the target genes, therefore can be used for SMA carrier screening. Moreover, it can also detect copy number of SMN2 exons 7 and 8, which can provide more information for genetic counseling.
Subject(s)
Humans , Female , Pregnancy , DNA Copy Number Variations , Reproducibility of Results , Muscular Atrophy, Spinal/genetics , Polymerase Chain Reaction/methods , Nucleic Acid Amplification Techniques , Survival of Motor Neuron 1 Protein/geneticsABSTRACT
BACKGROUND: Hepatitis B virus (HBV) remains a substantial public health safety concern drawing considerable attention in China and globally. The detection of HBV serological markers can enable the assessment of HBV infection and replication status in vivo and evaluate the body's protection against HBV. Therefore, this study aims to identify the epidemiological and clinical characteristics of HBV infection in children to prevent and control HBV infection in Wuhan areas. METHODS: We conducted an extensive retrospective cohort analysis of 115,029 individuals aged 0-18 years who underwent HBV serological markers detection for HBV infection in hospital between 2018 and 2021 using Electrochemiluminescence immunoassay. We generated descriptive statistics and analysed HBV infection's epidemiological and clinical characteristics between different sex and age groups. RESULTS: The overall positive detection rates of HBsAg, HBsAb, HBeAg, HBeAb, and HBcAb in all participants were 0.13%, 79.09%, 0.17%, 2.81%, and 5.82%, respectively. The positive rate of HBeAb and HBcAb in males was significantly lower than that in females (2.64% vs. 3.13%, 5.56% vs. 6.29%) (P < 0.05). Twenty-two distinct HBV serological expression patterns were revealed. Among them, 8 common expression patterns accounted for 99.63%, while the remaining 14 uncommon expression patterns were primarily observed in neonatal patients with HBV infection. There are no significant differences in serological patterns based on sex (P < 0.05). The overall HBV infection detection rate was 5.82% [range 5.68-5.95] and showed a declining yearly trend. The rate in females was higher than that in males 6.29% [6.05, 6.35] vs. 5.56% [5.39, 5.59]. The overall HBV diagnostic rate over 4 years was 0.20% [0.17, 0.22], and the rate declined yearly. The prevalence of acute infection was higher than that of other infection types before 2019, but the incidence of unclassified infection showed a significant upward trend after 2019. CONCLUSIONS: While the overall HBV infection detection rate in children has decreased year by year, the infection rate remains high in children under one year and between 4 and 18 years. This continued prevalence warrants heightened attention and vigilance.
Subject(s)
Hepatitis B virus , Hepatitis B , Male , Infant, Newborn , Female , Humans , Child , Retrospective Studies , Hepatitis B Surface Antigens , Hepatitis B/diagnosis , Hepatitis B/epidemiology , Hepatitis B/prevention & control , Hepatitis B AntibodiesABSTRACT
Aim: To investigate the thrifty effects of subanesthetic-dose S-ketamine on postoperative opioids and its safety and analgesic efficacy. Methods: Four-hundred and twenty patients were divided into the control group (CON group), the S-ketamine 0.2 mg/kg group (ES0.2 group), and the S-ketamine 0.3 mg/kg group (ES0.3 group) randomly. Major indicators include the Visual Analogue Scale (VAS), the times of compression with analgesic pumps after surgery, and analgesic drug consumption from anesthesia induction to 48 h after surgery. Minor records include vital signs, the use of vasoactive drugs, the Ramsay scores, the occurrence of adverse events including nervous system reaction, and the patient's satisfaction with anesthesia. Results: Compared with the CON group, VAS scores decreased in the ES0.2 and ES0.3 groups (p < 0.05). At 10 min after extubation, the VAS scores of the ES0.3 group were lower than that of the ES0.2 group (p < 0.05). The total number of compression with analgesic pumps of the ES0.3 group was lower than that of the CON group (p < 0.05). The opioid consumption after surgery of the ES0.3 group was lower than those of the CON group and the ES0.2 group (p < 0.05). The ES0.3 group's heart rate (HR) was faster but the use of vasoactive, drug consumption was less than the other two groups (p < 0.05). There were no significant differences in the incidence of postoperative adverse events and anesthetic satisfaction among the three groups. Conclusion: Subanesthetic-dose S-ketamine at 0.2-0.3 mg/kg especially the 0.3 mg/kg in general anesthesia induction can safely and effectively reduce postoperative pain and save postoperative opioid consumption.
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Abscess wound caused by bacterial infection is usually difficult to heal, thus greatly affect people's quality of life. In this study, a biodegradable drug-loaded microneedle patch (MN) is designed for targeted eradication of S. aureus infection and repair of abscess wound. Firstly, the bacterial responsive composite nanoparticle (Ce6@GNP-Van) with a size of about 182.6 nm is constructed by loading the photosensitizer Ce6 into gelatin nanoparticle (GNP) and coupling vancomycin (Van), which can specifically target S. aureus and effectively shield the phototoxicity of photosensitizer during delivery. When Ce6@GNP-Van is targeted and enriched in the infected regions, the gelatinase secreted by the bacteria can degrade GNP in situ and release Ce6, which can kill the bacteria by generating ROS under laser irradiation. In vivo experiments show that the microneedle is basically degraded in 10 min after inserting into skin, and the abscess wound is completely healed within 13 d after applying Ce6@GNP-Van-loaded MN patch to the abscess wound of the bacterial infected mice with laser irradiation, which can simultaneously achieve the eradication of biofilm and subsequent wound healing cascade activation, showing excellent synergistic antibacterial effect. In conclusion, this work establishes a synergistic treatment strategy to facilitate the repair of chronic abscess wound.
Subject(s)
Methicillin-Resistant Staphylococcus aureus , Photochemotherapy , Humans , Mice , Animals , Staphylococcus aureus , Photosensitizing Agents/pharmacology , Abscess/drug therapy , Quality of Life , Anti-Bacterial Agents/pharmacology , Vancomycin/pharmacologyABSTRACT
BACKGROUND: Optical coherence tomography angiography (OCTA) is a new and reliable machine used to evaluate retinal structure and macular perfusion in children. The use of OCTA under bad condition such as high altitude, low atmospheric oxygen, and low humidity, in children is rarely. AIM: To quantify the macular micro-vasculature in healthy children of various ages using OCTA in Qamdo. METHODS: Design: Prospective cross-sectional, school-based study. Three hundred and forty-seven normal students from 9 schools in 4 different areas in Qamdo were included. OCTA was performed on a 3 mm × 3 mm area centered on the macular region and macular cube 512 × 128 showed details in macular. Early treatment of diabetic retinopathy study Vessel Flow Density (VD) of the macular central vascular plexus density (CVD), inner vascular plexus density (IVD), full vascular plexus density (FVD), and the size of the foveal avascular zone (FAZ) were measured. All these results corrected by t/s = 3.382 × 0.01306 × (axial length-1.82). The differences were compared among various ages, sexes and living environments. RESULTS: The mean FAZ area in all eyes was 0.27 mm2 ± 0.12 mm2. The mean foveal thickness (MFT) in the macular cube was 227.64 µm ± 23.51 µm. Compared with girls, boys had a lager FAZ (P = 0.0029). Among the different age groups, MFT (P < 0.001) and FVD (P < 0.0001), IVD (P < 0.0001), and CVD (P = 0.0050) increased with age. FAZ areas were not correlated with age (P = 0.8853) or others (MFT, area). CONCLUSION: OCTA can use to evaluate macular perfusion in children. Our data bridge the gap between structural OCT and perfusion density in children in high altitude. Even though these were not a longitudinal study, it may provide us with hints about retina development during puberty and clinical implications of OCTA in children.
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OBJECTIVES: Two interlinked surveys were organised by the British Heart Foundation Data Science Centre, which aimed to establish national priorities for cardiovascular imaging research. METHODS: First a single time point public survey explored their views of cardiovascular imaging research. Subsequently, a three-phase modified Delphi prioritisation exercise was performed by researchers and healthcare professionals. Research questions were submitted by a diverse range of stakeholders to the question 'What are the most important research questions that cardiovascular imaging should be used to address?'. Of these, 100 research questions were prioritised based on their positive impact for patients. The 32 highest rated questions were further prioritised based on three domains: positive impact for patients, potential to reduce inequalities in healthcare and ability to be implemented into UK healthcare practice in a timely manner. RESULTS: The public survey was completed by 354 individuals, with the highest rated areas relating to improving treatment, quality of life and diagnosis. In the second survey, 506 research questions were submitted by diverse stakeholders. Prioritisation was performed by 90 researchers or healthcare professionals in the first round and 64 in the second round. The highest rated questions were 'How do we ensure patients have equal access to cardiovascular imaging when it is needed?' and 'How can we use cardiovascular imaging to avoid invasive procedures'. There was general agreement between healthcare professionals and researchers regarding priorities for the positive impact for patients and least agreement for their ability to be implemented into UK healthcare practice in a timely manner. There was broad overlap between the prioritised research questions and the results of the public survey. CONCLUSIONS: We have identified priorities for cardiovascular imaging research, incorporating the views of diverse stakeholders. These priorities will be useful for researchers, funders and other organisations planning future research.
Subject(s)
Quality of Life , Research , Humans , Exercise , Health Personnel , HeartABSTRACT
INTRODUCTION: This case report presents a rare occurrence of lupus mastitis affecting the breast. CASE PRESENTATION: An induration with mild discomfort was detected in the upper inner quadrant of the right breast of a 27-year-old Chinese woman with regular menstrual cycles. The patient is currently unmarried and has no previous history of full-term pregnancies or lactation. An ill-defined, subcutaneous, hyperechoic lesion with no calcification was visualized on breast ultrasound. Peripheral and internal blood flow signals demonstrated high intensity. Pathological analysis of a breast needle biopsy revealed fat lobule necrosis accompanied by mixed lymphoplasmacytic and histiocytic aggregates. CONCLUSION: The diagnosis of lupus mastitis necessitates a comprehensive evaluation of the patient's medical history, serological testing, imaging studies, and histopathological analysis.
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Vitamin D signaling via the Vitamin D Receptor (VDR) has been shown to protect against intestinal inflammation. Previous studies have also reported the mutual interactions of intestinal VDR and the microbiome, indicating a potential role of probiotics in modulating VDR expression. In preterm infants, although probiotics have been shown to reduce the incidence of necrotizing enterocolitis (NEC), they are not currently recommended by the FDA due to potential risks in this population. No previous studies have delved into the effect of maternally administered probiotics on intestinal VDR expression in early life. Using an infancy mouse model, we found that young mice exposed to maternally administered probiotics (SPF/LB) maintained higher colonic VDR expression than our unexposed mice (SPF) in the face of a systemic inflammatory stimulus. These findings indicate a potential role for microbiome-modulating therapies in preventing diseases such as NEC through the enhancement of VDR signaling.
Subject(s)
Enterocolitis, Necrotizing , Probiotics , Infant, Newborn , Humans , Animals , Mice , Receptors, Calcitriol/genetics , Receptors, Calcitriol/metabolism , Infant, Premature , Intestines , Enterocolitis, Necrotizing/prevention & control , Enterocolitis, Necrotizing/metabolism , Probiotics/pharmacology , Probiotics/therapeutic useABSTRACT
BACKGROUND: Fibroblast growth factor 21 (FGF21) is deemed to play an important role in kidney outcomes, while the association between FGF21 and various kidney diseases remains largely unclear and inconsistent. Therefore, we conducted this meta-analysis to find out the role of FGF21 in various renal diseases. METHODS: The outcome indicator of our study was assessed by the pooled standard mean difference (SMD) with 95% confidence intervals (CIs) which were calculated by random-effect model analysis. The risk of bias was assessed by Non-Randomized Studies of Interventions (ROBINS-I) tool. Funnel plot combined with Egger's and Begg's tests was performed to estimate the publication bias that existed in the study. RESULTS: A total of 28 eligible studies with 19348 participants were included in our research. The agreement between authors reached a kappa-value of 0.88. Overall, the serum FGF21 level was strongly higher in CKD patients (SMD = 0.97 (ng/L); 95% CI, 0.70-1.24 (ng/L)) and the renal outcomes in T2DM patients (SMD = 0.54 (ng/L); 95% CI, 0.39-0.70 (ng/L)) compared with the control group. Consistent with this, the incidence of CKD (OR = 2.56; 95% CI, 1.72-3.81) and the incidence of renal outcomes (OR = 1.63; 95% CI, 1.31-2.01) in T2DM patients was significantly higher in the patients with high FGF21 concentration, indicating that high serum FGF21 level may predict the incidence of CKD and the renal outcomes in T2DM patients. CONCLUSION: Serum FGF21 may be one of the strong predictors for various kidney diseases including the progression of CKD and the hard renal outcomes in type 2 diabetes patients, but more large-scale clinical research are needed to confirm this finding.
Subject(s)
Diabetes Mellitus, Type 2 , Renal Insufficiency, Chronic , Humans , Kidney/metabolism , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/metabolism , BiomarkersABSTRACT
Transposons are parasitic genetic elements that frequently hijack vital cellular processes of their host. HMGXB4 is a known Wnt signaling-regulating HMG-box protein, previously identified as a host-encoded factor of Sleeping Beauty (SB) transposition. Here, we show that HMGXB4 is predominantly maternally expressed, and marks both germinal progenitor and somatic stem cells. SB piggybacks HMGXB4 to activate transposase expression and target transposition to germinal stem cells, thereby potentiating heritable transposon insertions. The HMGXB4 promoter is located within an active chromatin domain, offering multiple looping possibilities with neighboring genomic regions. HMGXB4 is activated by ERK2/MAPK1, ELK1 transcription factors, coordinating pluripotency and self-renewal pathways, but suppressed by the KRAB-ZNF/TRIM28 epigenetic repression machinery, also known to regulate transposable elements. At the post-translational level, SUMOylation regulates HMGXB4, which modulates binding affinity to its protein interaction partners and controls its transcriptional activator function via nucleolar compartmentalization. When expressed, HMGXB4 can participate in nuclear-remodeling protein complexes and transactivate target gene expression in vertebrates. Our study highlights HMGXB4 as an evolutionarily conserved host-encoded factor that assists Tc1/Mariner transposons to target the germline, which was necessary for their fixation and may explain their abundance in vertebrate genomes.
Subject(s)
Chromosomes , DNA Transposable Elements , Animals , DNA Transposable Elements/genetics , Stem Cells , HMGB2 Protein/metabolismABSTRACT
The microbiota plays critical roles in regulating the function and health of the intestine and extraintestinal organs. A fundamental question is whether an intestinal-microbiome-breast axis exists during the development of breast cancer. If so, what are the roles of host factors? Vitamin D receptor (VDR) involves host factors and the human microbiome. Vdr gene variation shapes the human microbiome, and VDR deficiency leads to dysbiosis. We hypothesized that intestinal VDR protects hosts against tumorigenesis in the breast. We examined a 7,12-dimethylbenzanthracene (DMBA)-induced breast cancer model in intestinal epithelial VDR knockout (VDRΔIEC) mice with dysbiosis. We reported that VDRΔIEC mice with dysbiosis are more susceptible to breast cancer induced by DMBA. Intestinal and breast microbiota analysis showed that VDR deficiency leads to a bacterial profile shift from normal to susceptible to carcinogenesis. We found enhanced bacterial staining within breast tumors. At the molecular and cellular levels, we identified the mechanisms by which intestinal epithelial VDR deficiency led to increased gut permeability, disrupted tight junctions, microbial translocation, and enhanced inflammation, thus increasing tumor size and number in the breast. Furthermore, treatment with the beneficial bacterial metabolite butyrate or the probiotic Lactobacillus plantarum reduced breast tumors, enhanced tight junctions, inhibited inflammation, increased butyryl-CoA transferase, and decreased levels of breast Streptococcus bacteria in VDRΔIEC mice. The gut microbiome contributes to the pathogenesis of diseases not only in the intestine but also in the breast. Our study provides insights into the mechanism by which intestinal VDR dysfunction and gut dysbiosis lead to a high risk of extraintestinal tumorigenesis. Gut-tumor-microbiome interactions represent a new target in the prevention and treatment of breast cancer.
Subject(s)
Breast Neoplasms , Gastrointestinal Diseases , Gastrointestinal Microbiome , Humans , Mice , Animals , Female , Receptors, Calcitriol/genetics , Breast Neoplasms/prevention & control , Breast Neoplasms/metabolism , Dysbiosis/metabolism , Inflammation/metabolism , Carcinogenesis/metabolism , Cell Transformation, Neoplastic , Gastrointestinal Diseases/metabolism , Bacteria/metabolism , Intestinal Mucosa/microbiologyABSTRACT
OBJECTIVE: To explore clinical effect of intermittent flap opening technique in L-shaped incision of calcaneal fracture. METHODS: From January 2017 to January 2019, 48 patients with Sanders typeâ ¡ to â £ calcaneal fractures were treated by open reduction and internal fixation. According to different flap opening techniques, the patients were divided into control group and observation group, 24 patients in each group. In observation group, there were 17 males and 7 females, aged from 20 to 60 years old with an average of(45.12±9.56) years old;7 patients were typeâ ¡, 10 patients were type â ¢ and 7 patients were type â £ according to Sanders classification;3 patients were C0, 16 patients were C1 and 5 patients were C2 according to Tscherne-Gotzen soft-tissue assessment;treated with intermittent flap technique. In control group, there were 19 males and 5 females aged from 20 to 60 years old with an average of (47.32±10.67) years old;7 patients were typeâ ¡, 11 patients were type â ¢ and 6 patients were type â £ according to Sanders classification;2 patients were C0, 18 patients were C1 and 4 patients were C2 according to Tschemc-Gotzen soft-tissue assessment;treated with static flap opening technique. Operation time, flap retraction time, changes of Böhler angle and Gissane angle before and after operation at 3 days, and occurrence of incision complications were observed and compared between two groups. RESULTS: All patients were followed up from 3 to 6 months with an average of(4.52±1.01) months. There were no significant differences in operation time, changes of Böhler angle and Gissane angle before and after operation at 3 days between the two groups(P>0.05);there was statistical difference in flap retraction time between two groups(P<0.05). Occurrence of incision complications in observation group was significantly lower than that in control group (P<0.05). CONCLUSION: Intermittent flap opening technique is superior to static opening technique in reducing incision complications of lateral "L" approach of calcaneus. Single Kirschner wire opening does not affect the exposure, reduction and fixation of fracture during operation.
Subject(s)
Ankle Injuries , Calcaneus , Foot Injuries , Fractures, Bone , Knee Injuries , Surgical Wound , Male , Female , Humans , Young Adult , Adult , Middle Aged , Treatment Outcome , Fractures, Bone/surgery , Fracture Fixation, Internal/methods , Calcaneus/surgeryABSTRACT
OBJECTIVE: To investigate the clinical efficacy of needle-guided percutaneous cannulated compression screw fixation in the treatment of acute non-displaced scaphoid fracture of wrist. METHODS: The clinic data of twenty-eight patients with acute non-displaced scaphoid fracture from January 2014 to January 2019 were analyzed retrospectively. According to the intraoperative method of placement of cannulated screw, they were divided into Guide group(16 patients)and Conventional group(12 patients). There were 13 males and 3 females in Guide group, aged from 20 to 60 years old with an average of(31.42±9.71)years old;5 patients were classified as type A2, 3 patients were classified as type B1 and 8 patients were classified as type B2 according to Herbert classification;they were treated with percutaneous cannulated compression screw fixation under the guidance of needle. There were 11 males and 1 female in Conventional group, aged from 23 to 61 years old with an average of(30.51±7.52)years old;5 patients were classified as type A2, 2 patients were classified as type B1 and 5 patients were classified as type B2 according to Herbert classification;they were treated with conventional percutaneous cannulated compression screw fixation. The operation time, screw angle relative to the longitudinal axis of the scaphoid and wrist function score were assessed and compared between the two groups. RESULTS: A total of 28 patients were followed up from 20 to 45 months with an average of (33.00±8.72) months. None of patients had intraoperative complication and incision infection. These patients returned to work gradually 2 weeks after operation, and all fractures healed within 12 weeks. The operation time in the Guide group was significantly less than that in the Conventinal group(P<0.05). Screw angle relative to the longitudinal axis of the scaphoid in the Guide group was significantly smaller than that in the Conventional group(P<0.05). There was no significant difference in Mayo wrist function scores at the last follow-up between the two groups(P>0.05). During the follow-up period, none of the 28 patients showed internal fixation displacement, arthritis, scaphoid necrosis and other complications. CONCLUSION: In the treatment of acute non-displaced scaphoid fractures, the operation time of needle-guided percutaneous cannulated headless compression screw fixation is significantly shorter than that of conventional percutaneous screw fixation, and the screw axis is easier to be parallel to the longitudinal axis of the scaphoid.