Publications by authors named "Jiang Qian"

958 Publications

Quantitative T1 mapping MRI for the assessment of extraocular muscle fibrosis in thyroid-associated ophthalmopathy.

Endocrine 2021 Sep 21. Epub 2021 Sep 21.

Department of Ophthalmology, Fudan Eye & ENT Hospital, Shanghai, China.

Purpose: We aimed to investigate the performance of T1 mapping and its histological correlation with extraocular muscle fibrosis in thyroid-associated ophthalmopathy (TAO).

Methods: We prospectively recruited 12 cases of active TAO, 12 cases of inactive TAO, and 15 cases of control subjects. All participants underwent magnetic resonance imaging (MRI) scan with pre-/postcontrast T1 mapping and short-time inversion-recovery (STIR) sequence. The images were analyzed to obtain precontrast T1, extracellular-volume (ECV) fraction on T1 mapping, and signal-intensity ratio (SIR) on STIR for each rectus. Muscle biopsy was performed at lateral rectus to quantify-collagen volume fraction, glycosaminoglycan (GAG)-volume fraction, and extracellular space component. The relationship between MRI and histopathology was examined with Pearson correlation coefficient.

Results: The active TAO group was characterized with GAG accumulation, while the inactive TAO group presented with substantial fibrosis. The MRI parameters achieved acceptable interobserver and intraobserver agreement. The precontrast T1 and ECV remarkably increased in the TAO groups than the control group, and ECV positively correlated with collagen-volume fraction (r = 0.913) and extracellular-space component (r = 0.886) in the inactive TAO group. The SIR statistically increased in the active TAO group, and SIR positively correlated with GAG-volume fraction in all three groups. The performance of ECV (cutoff > 48.1%) to screen out extraocular muscle fibrosis in inactive TAO was 60.9% sensitivity and 93.3% specificity.

Conclusions: The ECV parameter on T1 mapping MRI is a reliable tool to quantify extraocular muscle fibrosis, providing insights into noninvasive evaluation of pathological changes in TAO orbit.

Trial Registration Number: ChiCTR2000040394; Date of registration: 28 November 2020.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12020-021-02873-0DOI Listing
September 2021

Fermented Cottonseed Meal as a Partial Replacement for Soybean Meal Could Improve the Growth Performance, Immunity and Antioxidant Properties, and Nutrient Digestibility by Altering the Gut Microbiota Profile of Weaned Piglets.

Front Microbiol 2021 1;12:734389. Epub 2021 Sep 1.

College of Animal Science and Technology, Hunan Agricultural University, Changsha, China.

The study investigated the impact of fermented cottonseed meal (FCSM) on growth performance, immunity and antioxidant properties, nutrient digestibility, and gut microbiota of weaned piglets by replacing soybean meal with FCSM in the diet. The experimental piglets were fed with either the soybean meal diet (SBM group) or fermented cottonseed meal diet (FCSM group) for 14days after weaning. The digestibility of dry matter (DM), organic matter (OM), crude protein (CP), gross energy (GE), amino acids and nitrogen was higher in the FCSM diet than those in the SBM diet (<0.05). The piglets in the FCSM group showed greater growth performance and lower diarrhea rate than those in the SBM group (<0.05). The concentration of serum immunoglobulin G (IgG) and antioxidase, intestinal and hepatic antioxidase were increased and the concentration of malondialdehyde (MDA) in the serum was decreased in those piglets in the FCSM group compared to those piglets in the SBM group (<0.05). The piglets in the FCSM group had a higher concentration of volatile fatty acids (VFAs) in their ileum and cecum and a higher Simpson index of ileum than piglets in the SBM group (<0.05). The relative abundance of and in ileum and , , and in cecum were enhanced in piglets fed with the FCSM diet, whereas the relative abundance of and were increased in piglets fed with the SBM diet. Overall, FCSM replacing SBM improved the growth performance, immunity and antioxidant properties, and nutrient digestibility; possibly the alterant gut microbiota and its metabolism of weaned piglets. Graphical AbstractFermented cottonseed meal as a partial replacement for soybean meal could improve the growth performance, immunity and antioxidant properties, and nutrient digestibility by altering the gut microbiota profile of weaned piglets. SBM, soybean meal; FCSM, fermented cottonseed meal.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2021.734389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440953PMC
September 2021

CO sequestration mediated by wollastonite in anaerobic digestion of sewage sludge: From sequence batch to semi-continuous operation.

Chemosphere 2021 Sep 4;287(Pt 3):132095. Epub 2021 Sep 4.

School of Environmental and Civil Engineering, Jiangnan University, Wuxi, 214122, China.

This study investigated the mechanisms involved in CO sequestration under the sequence batch and semi-continuous operation using wollastonite in sludge anaerobic digestion. Wollastonite substantially elevated CH content in biogas and played a role in CO capture. It increased biogas yield of the glucose due to pH buffering effect but did not increase that of the hydrolysate from thermal alkali pretreated sludge. Under the semi-continuous operation, wollastonite improved the CO sequestration, but decreased the biogas yield from 166 to 24 mL/g soluble chemical oxygen demand, since seemingly wollastonite residues inhibited microbes in the sludge. However, the use of dialysis bags to wrap wollastonite offset the negative impact of the wollastonite residues in the sludge, thereby increased biogas yield. The present study is conducive to understanding the mechanisms involved in and proving the feasibility of the CO sequestration using wollastonite in sludge anaerobic digestion and its impacts on long-term operation. Consequently, the findings of the study provide key parameters and useful guidelines for scaling up and wollastonite application in anaerobic digestion of sewage sludge.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chemosphere.2021.132095DOI Listing
September 2021

Irf6 participates in sevoflurane-induced perioperative neurocognitive disorder via modulating M2, but not M1 polarization of microglia.

Brain Res Bull 2021 Sep 15. Epub 2021 Sep 15.

Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China. Electronic address:

Perioperative neurocognitive disorder (PND) frequently occurs in elderly patients following anesthesia, and is associated with pro-inflammatory activation of microglia in hippocampus. In this study, sevoflurane, a commonly used inhaled anesthetic in clinic, was used to induce PND-like symptoms in aged SD rats (18-20 months). Data from novel object recognition and Y-maze tests first confirmed that aged SD rats exposed to 2% sevoflurane for 5h developed cognitive impairment. Microglia preferred to polarizing towards pro-inflammatory M1 subtype (iNOS+Iba-1+) in rat hippocampus post sevoflurane exposure, but not anti-inflammatory M2 subtype (Arg-1+Iba-1+). Microarray data identified interferon regulatory factor 6 (Irf6) as one (Fold change = -2.52, p = 0.006) of the 15 downregulated genes in hippocampus of the rats exposed to sevoflurane. Co-immunofluorescence data further illustrated that sevoflurane decreased Irf6 expression in hippocampal microglia. In vitro, sevoflurane enhanced lipopolysaccharide-induced M1 polarization of BV-2 cells and inhibited interleukin-4 induced M2 polarization. Interestingly, manipulation of Irf6 expression hardly affected M1 polarization. However, Irf6 overexpression further augmented the inhibitory effects on M2 polarization, and its silencing showed opposite effects. In addition, such M2 polarization-promoting effects of Irf6 knockdown may be associated with induction of peroxisome proliferator activated receptor gamma expression. Collectively, these findings suggest that Irf6 downregulation in hippocampal microglia may be a compensatory mechanism against sevoflurane-induced PND in the elderly.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.brainresbull.2021.09.012DOI Listing
September 2021

Diagnosis of Hirschsprung disease by hydrocolonic sonography in children.

Eur Radiol 2021 Sep 17. Epub 2021 Sep 17.

Department of Ultrasound, Capital Institute of Pediatrics, No. 2 Yabao Rd, Chaoyang District, Beijing, 100020, China.

Objectives: To compare hydrocolonic sonography with histopathology for diagnosing children with symptoms highly suggestive of Hirschsprung disease (HD).

Methods: In this prospective study, patients presenting refractory constipation highly suggestive of HD underwent hydrocolonic sonography with retrograde infusion of saline into the colon. The dilated segments, narrowed segments, luminal diameter ratio, transition zone (TZ), thickening, and blood perfusion of the upstream bowel were evaluated. The sensitivity and specificity of combined and single parameters were determined in comparison with biopsy.

Results: One hundred and three children were included in this study; 49 were confirmed to have HD. The luminal diameter ratio showed superiority over other parameters. An area under the curve (AUC) of 0.969 (95% confidence interval [CI]: 0.936-1.000) and a cutoff value of 1.51 were established by receiver operating characteristic (ROC) curve analysis of the luminal diameter ratio (sensitivity: 89.8%; specificity: 96.3%). By combining the luminal diameter ratio as the major criterion with two minor criteria, hydrocolonic sonography showed the same sensitivity (91.8%) and better specificity (96.3% vs 87%) than contrast enema, but this difference was not statistically significant (p = 0.063). Consistency analysis showed a kappa value of 0.825 (p < 0.001), indicating excellent agreement between hydrocolonic sonography and contrast enema.

Conclusions: Hydrocolonic sonography is a valuable diagnostic tool with both high sensitivity and specificity for HD diagnosis, allowing morphological and vascular assessments of the colon, and correlates well with contrast enema. In the appropriate setting, hydrocolonic sonography may be an alternative screening method for HD in a large group of children with constipation. Key Points • Hydrocolonic sonography is a simple, well-tolerated diagnostic tool with both high sensitivity and specificity for HD diagnosis. • Hydrocolonic sonography allows morphological and vascular assessments of the colon, and correlates well with contrast enema. • Hydrocolonic sonography is a possible alternative modality for paediatric patients highly suggestive of HD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00330-021-08287-wDOI Listing
September 2021

Risk Stratification of Cytogenetically Normal Acute Myeloid Leukemia With Biallelic Mutations Based on a Multi-Gene Panel and Nomogram Model.

Front Oncol 2021 17;11:706935. Epub 2021 Aug 17.

Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing, China.

Background: Approximately 30% of Chinese individuals with cytogenetically normal acute myeloid leukemia (CN-AML) have biallelic (bi) mutations. The prognosis and optimal therapy for these patients are controversial in clinical practice.

Methods: In this study, we performed targeted region sequencing of 236 genes in 158 individuals with this genotype and constructed a nomogram model based on leukemia-free survival (LFS). Patients were randomly assigned to a training cohort ( =111) and a validation cohort ( =47) at a ratio of 7:3. Risk stratification was performed by the prognostic factors to investigate the risk-adapted post-remission therapy by Kaplan-Meier method.

Results: At least 1 mutated gene other than was identified in patients and mutation number was associated with LFS (61.6% 39.0%, =0.033), survival (85.6% 62.9%,  =0.030) and cumulative incidence of relapse (CIR) (38.4% 59.5%, =0.0496). White blood cell count, mutations in , and DNA methylation related genes were weighted to construct a nomogram model and differentiate two risk subgroups. Regarding LFS, low-risk patients were superior to the high-risk (89.3% 33.8%, 0.001 in training cohort; 87.5% 18.2%, =0.009 in validation cohort). Compared with chemotherapy, allogenic hematopoietic stem cell transplantation (allo-HSCT) improved 5-year LFS (89.6% 32.6%, 0.001), survival (96.9% 63.6%, =0.001) and CIR (7.2% 65.8%, 0.001) in high-risk patients but not low-risk patients (LFS, 77.4% 88.9%, =0.424; survival, 83.9% 95.5%, =0.173; CIR, 11.7% 11.1%, =0.901).

Conclusions: Our study indicated that bi mutant-positive CN-AML patients could be further classified into two risk subgroups by four factors and allo-HSCT should be recommended for high-risk patients as post-remission therapy. These data will help physicians refine treatment decision-making in bi mutant-positive CN-AML patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.706935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415912PMC
August 2021

Low Intensity Focused Ultrasound Increases Duration of Anti-Nociceptive Responses in Female Common Peroneal Nerve Injury Rats.

Neuromodulation 2021 Sep 2. Epub 2021 Sep 2.

Department of Neuroscience and Experimental Therapeutics, Albany Medical College, Albany, NY, USA.

Objective: Chronic pain affects 7%-10% of Americans, occurs more frequently and severely in females, and available treatments have been shown to have less efficacy in female patients. Preclinical models addressing sex-specific treatment differences in the treatment of chronic pain have been limited. Here we examine the sex-specific effects of low intensity focused ultrasound (liFUS) in a modified sciatic nerve injury (SNI) model.

Materials And Methods: A modified SNI performed by ligating the common peroneal nerve (CPN) was used to measure sensory, behavioral pain responses, and nerve conduction studies in female and male rats, following liFUS of the L5 dorsal root ganglion.

Results: Using the same dose of liFUS in females and males of the same weight, CPN latency immediately after treatment was increased for 50 min in females compared to 25 min in males (p < 0.001). Improvements in mechanical pain thresholds after liFUS lasted significantly longer in females (seven days; p < 0.05) compared to males (three days; p < 0.05). In females, there was a significant improvement in depression-like behavior as a result of liFUS (N = 5; p < 0.01); however, because males never developed depression-like behavior there was no change after liFUS treatment.

Conclusions: Neuromodulation with liFUS has a greater effect in female rats on CPN latency, mechanical allodynia duration, and depression-like behavior. In order to customize neuromodulatory techniques for different patient phenotypes, it is essential to understand how they may alter sex-specific pathophysiologies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ner.13531DOI Listing
September 2021

Estrogen receptor β alleviates inflammatory lesions in a rat model of inflammatory bowel disease via down-regulating P2X7R expression in macrophages.

Int J Biochem Cell Biol 2021 Aug 28;139:106068. Epub 2021 Aug 28.

Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of the Ministry of Education, Division of Spine Surgery, Department of Orthopedics, Tongji Hospital Affiliated to Tongji University School of Medicine, Shanghai, 200065, People's Republic of China. Electronic address:

Estrogen receptor beta (ERβ) agonists could inhibit inflammation in animal models of inflammatory bowel disease (IBD). However, the mechanism underlying such effect and the potential role of P2 × 7 receptor (P2X7R) remains unclear. In the present study, we examined whether the effect of ERβ activation in IBD rats was related to P2X7R. Overexpression of ERβ using a recombinant lentivirus in IBD rats improved the IBD-like symptoms, including weight loss, disease activity index (DAI) scores, and inflammatory responses. ERβ agonists DPN and ERB-041 attenuated P2X7R expression in macrophages from colitis rats and in a murine macrophage cell line (RAW264.7) in response to either lipopolysaccharide (LPS) or adenosine triphosphate (ATP). DPN and ERB-041 also blocked increased production of TNF-α, IL-6, and IL-1β in the rectocolon of colitis rats. The two ERβ agonists reversed LPS- and ATP-induced up-regulation of P2X7R and its downstream proteins, including NLRP3, ASC, caspase-1, and pro-IL-1β, in RAW264.7 cells. Also, in both the rectocolon of colitis rats and RAW264.7 cells, ERβ agonists reversed the up-regulation of extracellular regulated protein kinases (ERK), the Janus kinase 2 (JAK2), and signal transducer and activator of transcription 3 (STAT3), but not up-regulation of serine threonine kinase or cAMP-response element binding protein (CREB). Blockade of JAK2 or STAT3 phosphorylation significantly reduced the ability of DPN to down-regulate P2X7R expression and the ability of ERB-041 and DPN to inhibit IL-1β release from RAW264.7 cells. We found that ERβ and P2X7R co-localized in the macrophages of rat rectocolon and in RAW264.7 cells. Deletion of macrophages from colitis rats with clodronate abolished the inhibitory effect of DPN. These results suggest that ERβ plays an important anti-inflammatory role in IBD rats by down-regulating P2X7R expression and inhibiting IL-1β release from macrophages through the JAK2/STAT3 signaling pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biocel.2021.106068DOI Listing
August 2021

Epithelial to mesenchymal transition (EMT) of human stem cell-derived retinal pigment epithelium shares commonalities with malignancy-associated EMT: a proteomic analysis.

Mol Cell Proteomics 2021 Aug 26:100131. Epub 2021 Aug 26.

Department of Ophthalmology, Stem Cell Ocular Regenerative Medicine Center, Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Solomon H. Snyder Department of Neuroscience, Department of Molecular Biology and Genetics, Department of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Institute for NanoBioTechnology, Johns Hopkins University, Whiting School of Engineering Baltimore, MD 21218, USA. Electronic address:

Stress and injury to the retinal pigment epithelium (RPE) often lead to de-differentiation and epithelial to mesenchymal transition (EMT). These processes have been implicated in several retinal diseases, including proliferative vitreoretinopathy (PVR), diabetic retinopathy (DR), and age-related macular degeneration (AMD). Despite the importance of RPE-EMT and the large body of data characterizing malignancy-related EMT, comprehensive proteomic studies to define the protein changes and pathways underlying RPE-EMT have not been reported. This study sought to investigate the temporal protein expression changes that occur in a human induced pluripotent stem cell (iPSC)-based RPE-EMT model. We utilized multiplexed isobaric tandem mass tag (TMT) labeling followed by high-resolution tandem mass spectrometry for precise and in-depth quantification of the RPE-EMT proteome. We have identified and quantifed 7,937 protein groups in our TMT-based mass spectrometry analysis. We observed a total of 532 proteins that are differentially regulated during RPE-EMT. Further, we integrated our proteomic data with prior transcriptomic (RNA-seq) data to provide additional insights into RPE-EMT mechanisms. To validate these results, we have performed a label free single shot data-independent acquisition (DIA) mass spectrometry study. Our integrated analysis indicates both the commonality and uniqueness of RPE-EMT compared with malignancy-associated EMT. Our comparative analysis also revealed that multiple AMD-associated risk factors are differentially regulated during RPE-EMT. Together, our integrated dataset provides a comprehensive RPE-EMT atlas and resource for understanding the molecular signaling events and associated biological pathways that underlie RPE-EMT onset. This resource has already facilitated the identification of chemical modulators that could inhibit RPE-EMT, and it will hopefully aid in ongoing efforts to develop EMT inhibition as an approach for the treatment of retinal disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.mcpro.2021.100131DOI Listing
August 2021

Altered gut microbiome compositions are associated with the severity of asthma.

J Thorac Dis 2021 Jul;13(7):4322-4338

National Heart & Lung Institute, Imperial College London & Biomedical Research Unit, Royal Brompton & Harefield NHS Trust, London, UK.

Background: Despite substantial evidence on the contribution of the diversity of the gut microbiome to the pathogenesis of asthma and allergic diseases, little is known about their relationship with asthma severity and/or clinical phenotypes. We analyzed the difference in composition of the gut microbiome between subjects with asthma and healthy subjects and explored its role in the development of asthma.

Methods: Fecal samples from 15 subjects with severe asthma (SA), 14 with non-severe asthma (NSA), and 15 healthy subjects were assessed by 16S ribosomal RNA gene sequencing methods to identify the gut bacterial composition.

Results: Compared with those in the NSA group, patients in the SA group had a higher dose of inhaled corticosteroids, and there were more atopic subjects (60% 35.7%, respectively). No significant differences were found at the phylum level either in operational taxonomic unit numbers or in diversity scores among the SA, NSA, and healthy groups. However, at the family level, the relative abundance of in the SA group was remarkedly lower than that in the group with healthy subjects (P<0.05). Furthermore, and were significantly more common in samples from the SA group than in those from the NSA group (P<0.05). In the SA group, positive correlations were observed between the relative abundance of and mid-expiratory flow 25% (MEF25%) predicted (r=0.538, P=0.047), as well as between the relative abundance of and body mass index (r=0642, P=0.010). Principal component analysis suggested that the relative abundances of and were associated with severe asthma. Moreover, we found that class , order , and family were significantly different among the groups defined by serum immunoglobulin E (IgE) levels.

Conclusions: Our findings suggest that altered gut microbiome compositions are involved in the severity of asthma and that there are specific bacteria related to different asthma phenotypes in terms of serum IgE levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/jtd-20-2189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339736PMC
July 2021

Surgical approach and functional outcome of redo pull-through for postoperative complications in Hirschsprung's disease.

Pediatr Surg Int 2021 Oct 20;37(10):1401-1407. Epub 2021 Aug 20.

Department of General Surgery, Capital Institute of Pediatrics, Beijing, China.

Aim: To review our surgical experience and outcome of redo pull-through for various postoperative complications of Hirschsprung's disease.

Methods: A retrospective study was performed on children who underwent redo pull-through from 2016 to 2019. Operative methods and functional outcomes were compared between those with anastomotic complications (stricture and fistula, n = 12) and patients without anastomotic complications (n = 24) such as residual aganglionosis/transition zone, twisted pull-through and tight soave cuff.

Result: 36 Patients (29 male and 7 female) were included with median age 6 (0.1-54) months at primary and 36 (9-144) months at redo pull-through. A transanal rectal mucosectomy and partial internal anal sphincterectomy (TRM-PIAS) pull-through with laparoscopic (n = 10, 27.8%) or laparotomy (n = 26, 72.2%) assisted techniques were performed for all patients during redo procedure. Patients with anastomotic complications had lower incidence of successful laparoscopic pull-through (0%), higher postoperative complications (25%) after redo surgery, but similar functional outcomes compared to those without anastomotic complications (41.6% underwent laparoscopic surgery, 4.2% complications). Patients with partial colectomy had significantly less soiling (36.4%) and enterocolitis (0%) compared to those with subtotal/total colectomy (79.2% soiling and 58.3% enterocolitis).

Conclusion: TRM-PIAS with/without laparoscopic-assisted redo pull-through was effective in treating various complications after primary pull-through. The functional outcome is strongly associated with the length of residual colon after redo pull-though.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00383-021-04965-4DOI Listing
October 2021

Is the Sokal or EUTOS long-term survival (ELTS) score a better predictor of responses and outcomes in persons with chronic myeloid leukemia receiving tyrosine-kinase inhibitors?

Leukemia 2021 Aug 19. Epub 2021 Aug 19.

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, PR China.

Data from 1661 consecutive subjects with chronic-phase chronic myeloid leukemia (CML) receiving initial imatinib (n = 1379) or a 2-generation tyrosine-kinase inhibitor (2G-TKI; n = 282) were interrogated to determine whether the Sokal or European Treatment and Outcome Study for CML (EUTOS) long-term survival (ELTS) scores were more accurate responses and outcome predictors. Both scores predicted probabilities of achieving complete cytogenetic response (CCyR), major molecular response (MMR), failure- and progression-free survivals (FFS, PFS), and survival in all subjects and those receiving imatinib therapy. However, the ELTS score was a better predictor of MR, MR, and CML-related survival than the Sokal score. In subjects receiving 2G-TKI therapy, only the ELTS score accurately predicted probabilities of CCyR, MMR, MR, FFS, and PFS. In the propensity score matching, subjects classified as intermediate risk by the ELTS score receiving a 2G-TKI had better responses (p < 0.001~0.061), FFS (p = 0.002), and PFS (p = 0.03) but not survival. Our data suggest better overall prediction accuracy for the ELTS score compared with the Sokal score in CML patients, especially those receiving 2G-TKIs. People identified as intermediate risk by the ELTS score may benefit more from initial 2G-TKI therapy in achieving surrogate endpoints but not survival, especially when a briefer interval to stopping TKI therapy is the therapy objective.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41375-021-01387-yDOI Listing
August 2021

Prognostic significance of TIM-3 expression pattern at diagnosis in patients with t(8;21) acute myeloid leukemia.

Leuk Lymphoma 2021 Aug 18:1-10. Epub 2021 Aug 18.

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing, China.

Acute myeloid leukemia (AML) with t(8;21) is a heterogeneous disease and needs to be stratified. Both, cancer cells and immune cells participate in tumor initiation, growth and progression and might affect clinical outcomes. TIM-3 (T cell immunoglobulin and mucin domain-containing protein 3), an immune checkpoint molecule, is expressed not only on immune cells but also on leukemic stem cells (LSCs) in AML. This prompted us to investigate the prognostic significance of TIM-3 in t(8;21) AML. A total of 47 t(8;21) AML patients were tested for TIM-3 expression by multi-parameter flow cytometry at diagnosis. 35 of these, who received chemotherapy alone or along with allogeneic hematopoietic stem cell transplantation were followed up. The expression pattern of TIM-3 on T-cells and NK (natural killer) cells as a whole (T + NK) and LSCs were evaluated independently. High percentage of T + NK - TIM-3 and CD34CD38TIM-3 cells were significantly associated with a high 2-year cumulative incidence of relapse (CIR) ( = 0.028, 0.016). Further, concurrent high frequencies of T + NK-TIM-3 and CD34CD38TIM-3 cells at diagnosis were significantly associated with a high 2-year CIR ( < 0.0001) and this together with c-KIT D816 mutation were the independent adverse prognostic factors for relapse (hazard ratio (HR)=2.5, [95% confidence interval (CI), 1.1-6.0],  = 0.04; HR = 46.5, [95% CI, 2.7-811.5],  = 0.009). In conclusion, the expression pattern of TIM-3 on both T and NK cells and LSCs at diagnosis had prognostic significance in t (8;21) AML.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10428194.2021.1966785DOI Listing
August 2021

PML-RARA transcript levels at the end of induction therapy are associated with prognosis in non-high-risk acute promyelocytic leukaemia with all-trans retinoic acid plus arsenic in front-line therapy: long-term follow-up of a single-centre cohort study.

Br J Haematol 2021 Aug 17. Epub 2021 Aug 17.

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.

Despite the high cure probability for acute promyelocytic leukaemia (APL), a minority of patients will relapse and the risk factors for relapse are unclear. We retrospectively analysed 212 patients who were diagnosed with non-high-risk APL and received all-trans retinoic acid (ATRA) plus arsenic as front-line therapy at Peking University Institute of Hematology from February 2014 to December 2018. A total of 176 patients (83%) received oral arsenic (realgar-indigo naturalis formula) plus ATRA, 36 patients (17%) received arsenic trioxide plus ATRA and 203 patients were evaluable for relapse. After a median (range) follow-up of 53·6 (24·3-85·4) months, two patients had molecular relapse and eight had haematological relapse. A promyelocytic leukaemia/retinoic acid receptor alpha (PML-RARA) transcript level of ≥6·5% at the end of induction therapy was associated with relapse (P = 0·031). The 5-year cumulative incidence of relapse, event-free survival and overall survival were 5·5%, 92·3% and 96·3% respectively. In conclusion, the present long-term follow-up study further confirmed the high cure probability of ATRA plus oral arsenic as front-line therapy for non-high-risk APL and showed that the PML-RARA transcript level at the end of induction therapy was associated with relapse.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bjh.17752DOI Listing
August 2021

Delayed hypersensitivity reaction to a dural repair substitute.

Br J Neurosurg 2021 Aug 16:1-4. Epub 2021 Aug 16.

Department of Neurosurgery, Albany Medical Center, Albany, NY, USA.

Background: Modern neurosurgeons commonly rely on dural grafts to aid in obtaining watertight closures when the native dura itself cannot be approximated.

Case Presentation: We present a patient who developed a symptomatic, delayed hypersensitivity reaction to a cellulose-based synthetic dural graft, which resolved after reoperation and removal of the graft.

Discussion: Dural grafts are a safe and common implant utilized in neurosurgery. Nevertheless, as with all implanted material, there is a chance for symptomatic immune reactions to occur.

Conclusion: This type of response is exceedingly uncommon, but recognition of this rare presentation may help other providers recognize it in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/02688697.2021.1967879DOI Listing
August 2021

Health-adjusted life expectancy (HALE) in Chongqing, China, 2017: An artificial intelligence and big data method estimating the burden of disease at city level.

Lancet Reg Health West Pac 2021 Apr 2;9:100110. Epub 2021 Mar 2.

Ping An Technology (Shenzhen) Co., Ltd., Ping'an International Financial Center, Futian District, Shenzhen 518001, China.

Background: A universally applicable approach that provides standard HALE measurements for different regions has yet to be developed because of the difficulties of health information collection. In this study, we developed a natural language processing (NLP) based HALE estimation approach by using individual-level electronic medical records (EMRs), which made it possible to calculate HALE timely in different temporal or spatial granularities.

Methods: We performed diagnostic concept extraction and normalisation on 13•99 million EMRs with NLP to estimate the prevalence of 254 diseases in WHO Global Burden of Disease Study (GBD). Then, we calculated HALE in Chongqing, 2017, by using the life table technique and Sullivan's method, and analysed the contribution of diseases to the expected years "lost" due to disability (DLE).

Findings: Our method identified a life expectancy at birth (LE) of 77•9 years and health-adjusted life expectancy at birth (HALE) of 71•7 years for the general Chongqing population of 2017. In particular, the male LE and HALE were 76•3 years and 68•9 years, respectively, while the female LE and HALE were 80•0 years and 74•4 years, respectively. Cerebrovascular diseases, cancers, and injuries were the top three deterioration factors, which reduced HALE by 2•67, 2•15, and 1•19 years, respectively.

Interpretation: The results demonstrated the feasibility and effectiveness of EMRs-based HALE estimation. Moreover, the method allowed for a potentially transferable framework that facilitated a more convenient comparison of cross-sectional and longitudinal studies on HALE between regions. In summary, this study provided insightful solutions to the global ageing and health problems that the world is facing.

Funding: National Key R and D Program of China (2018YFC2000400).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lanwpc.2021.100110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315391PMC
April 2021

Primary Intramedullary Spinal Melanoma: A Rare Disease of the Spinal Cord.

Cureus 2021 Jul 5;13(7):e16194. Epub 2021 Jul 5.

Hematology and Medical Oncology, Albany Medical Center, Albany, USA.

Primary malignant melanoma of the intramedullary region of the spinal cord has rarely been reported in the literature. These tumors can have variable appearance on magnetic resonance imaging (MRI) due to different extents of melanin and hemorrhage. Histopathologic confirmation and a comprehensive workup to rule out extra-spinal melanoma are required to make definitive diagnosis. We present a case of a patient diagnosed with primary intramedullary spinal melanoma in his lower thoracic spinal cord who was effectively treated with surgical resection, adjuvant radiation, and adjuvant immunotherapy. Gross total resection (GTR) is most vital in the management of this spinal tumor. Although several studies have established the efficacy of immunotherapy agents in advanced malignant melanoma, the use of these agents has not been studied in primary central nervous system melanomas. This case provides insight into the diagnostic approach and treatment options for this unique malignancy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7759/cureus.16194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336382PMC
July 2021

Algae biochar enhanced methanogenesis by enriching specific methanogens at low inoculation ratio during sludge anaerobic digestion.

Bioresour Technol 2021 Oct 4;338:125493. Epub 2021 Jul 4.

School of Environmental and Civil Engineering, Jiangnan University, Wuxi 214122, China; Jiangsu Key Laboratory of Anaerobic Biotechnology, Wuxi 214122, China; Jiangsu Collaborative Innovation Center of Water Treatment Technology and Material, Suzhou 215011, China. Electronic address:

Carbon materials are promising in improving the performance of anaerobic digestion, however, interactive mechanisms between the carbon-based enhancement and operating parameters remained unclear. Using anaerobic digested sludge as inoculum, the effects of Taihu blue algae biochar (ABC) on methanogenesis at different inoculation ratios were investigated during sludge anaerobic digestion. Results showed that ABC enhanced methane productions at the lower inoculation ratios (4% and 1%, v/v), but not at the higher ratio (10%, v/v). Mechanism analysis demonstrated methanogenic improvements at the lower inoculation ratios were not owing to initial organic loading rate increments. Otherwise, ABC addition at the lower inoculation ratios were more favorable for the enrichment of Methanosarcina than the higher ratio, which might be benefit for methanogenesis through directed interspecies electron transfer. Thus, for the improvement of sludge anaerobic digestion, the microbial enrichments at different inoculation ratios would be more important than the merely biochar addition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biortech.2021.125493DOI Listing
October 2021

Genome assembly of the Chinese maize elite inbred line RP125 and its EMS mutant collection provide new resources for maize genetics research and crop improvement.

Plant J 2021 Jul 12. Epub 2021 Jul 12.

Maize Research Institute, Sichuan Agricultural University, ChengDu, 611130, China.

Maize is an important crop worldwide, as well as a valuable model with vast genetic diversity. Accurate genome and annotation information for a wide range of inbred lines would provide valuable resources for crop improvement and pan-genome characterization. In this study, we generated a high-quality de novo genome assembly (contig N50 of 15.43 Mb) of the Chinese elite inbred line RP125 using Nanopore long-read sequencing and Hi-C scaffolding, which yield highly contiguous, chromosome-length scaffolds. Global comparison of the RP125 genome with those of B73, W22, and Mo17 revealed a large number of structural variations. To create new germplasm for maize research and crop improvement, we carried out an EMS mutagenesis screen on RP125. In total, we obtained 5818 independent M2 families, with 946 mutants showing heritable phenotypes. Taking advantage of the high-quality RP125 genome, we successfully cloned 10 mutants from the EMS library, including the novel kernel mutant qk1 (quekou: "missing a small part" in Chinese), which exhibited partial loss of endosperm and a starch accumulation defect. QK1 encodes a predicted metal tolerance protein, which is specifically required for Fe transport. Increased accumulation of Fe and reactive oxygen species as well as ferroptosis-like cell death were detected in qk1 endosperm. Our study provides the community with a high-quality genome sequence and a large collection of mutant germplasm.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/tpj.15421DOI Listing
July 2021

Primary angle closure glaucoma is characterized by altered extracellular matrix homeostasis in the iris.

Proteomics Clin Appl 2021 Jul 9:e2000094. Epub 2021 Jul 9.

Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Purpose: To characterize the proteome of the iris in primary angle closure glaucoma (PACG).

Experimental Design: In this cross-sectional study, iris samples were obtained from surgical iridectomy of 48 adults with PACG and five normal controls. Peptides from iris were analysed using liquid chromatography-tandem mass spectrometry on an Orbitrap Q Exactive Plus mass spectrometer. Verification of proteins of interest was conducted using selected reaction monitoring on a triple quadrupole mass spectrometer. The main outcome was proteins with a log two-fold difference in expression in iris between PACG and controls.

Results: There were 3,446 non-redundant proteins identified in human iris, of which 416 proteins were upregulated and 251 proteins were downregulated in PACG compared with controls. Thirty-two upregulated proteins were either components of the extracellular matrix (ECM) (fibrillar collagens, EMILIN-2, fibrinogen, fibronectin, matrilin-2), matricellular proteins (thrombospondin-1), proteins involved in cell-matrix interactions (integrins, laminin, histidine-rich glycoprotein, paxillin), or protease inhibitors known to modulate ECM turnover (α-2 macroglobulin, tissue factor pathway inhibitor 2, papilin). Two giant proteins, titin and obscurin, were up- and down-regulated, respectively, in the iris in PACG compared with controls.

Conclusions And Clinical Relevance: This proteomic study shows that ECM composition and homeostasis are altered in the iris in PACG.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/prca.202000094DOI Listing
July 2021

βA3/A1-crystallin regulates apical polarity and EGFR endocytosis in retinal pigmented epithelial cells.

Commun Biol 2021 07 8;4(1):850. Epub 2021 Jul 8.

Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

The retinal pigmented epithelium (RPE) is a monolayer of multifunctional cells located at the back of the eye. High membrane turnover and polarization, including formation of actin-based apical microvilli, are essential for RPE function and retinal health. Herein, we demonstrate an important role for βA3/A1-crystallin in RPE. βA3/A1-crystallin deficiency leads to clathrin-mediated epidermal growth factor receptor (EGFR) endocytosis abnormalities and actin network disruption at the apical side that result in RPE polarity disruption and degeneration. We found that βA3/A1-crystallin binds to phosphatidylinositol transfer protein (PITPβ) and that βA3/A1-crystallin deficiency diminishes phosphatidylinositol 4,5-biphosphate (PI(4,5)P), thus probably decreasing ezrin phosphorylation, EGFR activation, internalization, and degradation. We propose that βA3/A1-crystallin acquired its RPE function before evolving as a structural element in the lens, and that in the RPE, it modulates the PI(4,5)P pool through PITPβ/PLC signaling axis, coordinates EGFR activation, regulates ezrin phosphorylation and ultimately the cell polarity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s42003-021-02386-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266859PMC
July 2021

Interferon-α as maintenance therapy can significantly reduce relapse in patients with favorable-risk acute myeloid leukemia.

Leuk Lymphoma 2021 Jul 1:1-8. Epub 2021 Jul 1.

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Centre for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.

To evaluate the efficacy of interferon-α (IFN-α) as maintenance therapy in patients with favorable-risk acute myeloid leukemia (AML), this retrospective study enrolled 84 patients with favorable-risk AML: 42 patients who received IFN-α maintenance therapy and 42 patients who did not (control). The median follow-up time and duration of IFN-α treatment was 26 (6-54) months and 18 (2-24) months, respectively. The 4-year estimated relapse-free survival (RFS) after the last consolidation chemotherapy was 86.8% (95% confidence interval (CI), 75.8-97.8%) in the IFN-α group and 55.7% (95% CI, 37.2-74.3%) in the control group (=.007). The 4-year estimated overall survival was 94.4% (95% CI, 86.8-102%) and 76.4% (95% CI, 61.9-90.9%) in IFN-α and control groups, respectively (=.040). The Cox regression analysis showed that IFN-α treatment was the only independent factor affecting RFS (=.004). Maintenance therapy with IFN-α may prevent relapse in favorable-risk AML after consolidation chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10428194.2021.1948027DOI Listing
July 2021

Large-scale phenotypic drug screen identifies neuroprotectants in zebrafish and mouse models of retinitis pigmentosa.

Elife 2021 06 29;10. Epub 2021 Jun 29.

Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University, Baltimore, United States.

Retinitis pigmentosa (RP) and associated inherited retinal diseases (IRDs) are caused by rod photoreceptor degeneration, necessitating therapeutics promoting rod photoreceptor survival. To address this, we tested compounds for neuroprotective effects in multiple zebrafish and mouse RP models, reasoning drugs effective across species and/or independent of disease mutation may translate better clinically. We first performed a large-scale phenotypic drug screen for compounds promoting rod cell survival in a larval zebrafish model of inducible RP. We tested 2934 compounds, mostly human-approved drugs, across six concentrations, resulting in 113 compounds being identified as hits. Secondary tests of 42 high-priority hits confirmed eleven lead candidates. Leads were then evaluated in a series of mouse RP models in an effort to identify compounds effective across species and RP models, that is, potential pan-disease therapeutics. Nine of 11 leads exhibited neuroprotective effects in mouse primary photoreceptor cultures, and three promoted photoreceptor survival in mouse retinal explants. Both shared and complementary mechanisms of action were implicated across leads. Shared target tests implicated -dependent cell death in our zebrafish RP model. Complementation tests revealed enhanced and additive/synergistic neuroprotective effects of paired drug combinations in mouse photoreceptor cultures and zebrafish, respectively. These results highlight the value of cross-species/multi-model phenotypic drug discovery and suggest combinatorial drug therapies may provide enhanced therapeutic benefits for RP patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7554/eLife.57245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425951PMC
June 2021

Predictive model based on gene and laboratory data for intravenous immunoglobulin resistance in Kawasaki disease in a Chinese population.

Pediatr Rheumatol Online J 2021 Jun 26;19(1):95. Epub 2021 Jun 26.

Department of Cardiology, Children's Hospital Capital Institute of Pediatrics, No. 2 Ya-Bao Road, Chao Yang District, Beijing, 100020, China.

Background: Here, we investigated the predictive efficiency of a newly developed model based on single nucleotide polymorphisms (SNPs) and laboratory data for intravenous immunoglobulin (IVIG) resistance in Kawasaki disease (KD) in a Chinese population.

Methods: Data relating to children with KD were acquired from a single center between December 2015 and August 2019 and used to screen target SNPs. We then developed a predictive model of IVIG resistance using previous laboratory parameters. We then validated our model using data acquired from children with KD attending a second center between January and December 2019.

Results: Analysis showed that rs10056474 GG, rs746994GG, rs76863441GT, rs16944 (CT/TT), and rs1143627 (CT/CC), increased the risk of IVIG-resistance in KD patients (odds ratio, OR > 1). The new predictive model, which combined SNP data with a previous model derived from laboratory data, significantly increased the area under the receiver-operator-characteristic curves (AUC) (0.832, 95% CI: 0.776-0.878 vs 0.793, 95%CI:0.734-0.844, P < 0.05) in the development dataset, and (0.820, 95% CI: 0.730-0.889 vs 0.749, 95% CI: 0.652-0.830, P < 0.05) in the validation dataset. The sensitivity and specificity of the new assay were 65.33% (95% CI: 53.5-76.0%) and 86.67% (95% CI: 80.2-91.7%) in the development dataset and 77.14% (95% CI: 59.9-89.6%) and 86.15% (95% CI: 75.3-93.5%) in the validation dataset.

Conclusion: Analysis showed that rs10056474 and rs746994 in the SMAD5 gene, rs76863441 in the PLA2G7 gene, and rs16944 or rs1143627 in the interleukin (IL)-1B gene, were associated with IVIG resistant KD in a Chinese population. The new model combined SNPs with laboratory data and improved the predictve efficiency of IVIG-resistant KD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12969-021-00582-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236184PMC
June 2021

Mental Health in Persons With Chronic Myeloid Leukemia During the SARS-CoV-2 Pandemic: The Need for Increased Access to Health Care Services.

Front Psychiatry 2021 8;12:679932. Epub 2021 Jun 8.

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing, China.

Mental health problems in the general population have been reported during the SARS-CoV-2 pandemic; however, there were rare data in persons with chronic myeloid leukemia (CML). Therefore, we performed a cross-sectional study on mental health evaluated using the 9-item Patient Health Questionnaire (PHQ-9; depression), the 7-item Generalized Anxiety Disorder (GAD-7; anxiety), and the 22-item Impact of Event Scale-Revised (IES-R; distress), including subscales of avoidance, intrusion, and hyper-arousal in persons with CML, non-cancer persons, and immediate family members of persons with cancer as controls (≥16 years) by an online survey. Data from 3,197 persons with CML and 7,256 controls were collected. In multivariate analyses, CML was significantly associated with moderate to severe depression (OR = 1.6; 95% Confidence Interval [CI], 1.4, 1.9; < 0.001), anxiety (OR = 1.4 [1.1, 1.7]; = 0.001), distress (OR = 1.3 [1.1, 1.5]; < 0.001), and hyper-arousal (OR = 1.5 [1.3, 1.6]; < 0.001). Moreover, delay in regular monitoring was significantly associated with depression (OR 1.3 [1.0, 1.7]; = 0.024), anxiety (OR = 1.3 [1.0, 1.8]; = 0.044), avoidance (OR = 1.2 [1.0, 1.4]; = 0.017), and intrusion (OR = 1.2 [1.0, 1.4]; = 0.057); tyrosine kinase-inhibitor dose reduction or discontinuation, depression (OR = 1.9 [1.3, 2.8]; = 0.001), distress (OR = 2.0 [1.4, 2.8]; < 0.001), avoidance (OR = 1.6 [1.2, 2.1]; = 0.004), intrusion (OR = 1.6 [1.1, 2.1]; = 0.006), and hyper-arousal (OR = 1.3 [1.0, 1.8]; = 0.088). We concluded that persons with CML during the SARS-CoV-2 pandemic have worse mental health including depression, anxiety, and distress symptoms. Decreasing or stopping monitoring or dose resulted in adverse mental health consequences.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpsyt.2021.679932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217438PMC
June 2021

Novel Bioactive Glass-Modified Hybrid Composite Resin: Mechanical Properties, Biocompatibility, and Antibacterial and Remineralizing Activity.

Front Bioeng Biotechnol 2021 1;9:661734. Epub 2021 Jun 1.

Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.

Secondary caries seriously limits the lifetime of composite resin. However, integrating all desirable properties (i.e., mechanical, antibacterial, bioactivity, and biocompatibility) into one composite resin is still challenging. Herein, a novel bioactive glass (BAG)-modified hybrid composite resin has been successfully developed to simultaneously achieve excellent mechanical properties, good biocompatibility, and antibacterial and remineralizing capabilities. When the mass fractions of BAG particles were added from 8 to 23 wt %, the original mechanical properties of the composite resin, including flexural strength and compressive strength, were not obviously affected without compromising the degree of conversion. Although the BAG incorporation of mass fractions of 16 wt % to 23 wt % in composite resins reduced cell viability, the viability could be recovered to normal by adjusting the pH value. Moreover, the BAG-modified composite resins that were obtained showed good antibacterial effects against and enhanced remineralizing activity on demineralized dentin surfaces with increasing incorporation of BAG particles. The possible mechanisms for antibacterial and remineralizing activity might be closely related to the release of bioactive ions (Ca, Si), suggesting that its antibacterial and biological properties can be controlled by modulating the amounts of bioactive ions. The capability to balance the mechanical properties, cytotoxicity, antibacterial activity, and bioactivity makes the BAG-modified composite resin a promising prospect for clinical application. Our findings provide insight into better design and intelligent fabrication of bioactive composite resins.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fbioe.2021.661734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205519PMC
June 2021

3D genome alterations associated with dysregulated HOXA13 expression in high-risk T-lineage acute lymphoblastic leukemia.

Nat Commun 2021 06 17;12(1):3708. Epub 2021 Jun 17.

The MOE Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University, Beijing, China.

3D genome alternations can dysregulate gene expression by rewiring enhancer-promoter interactions and lead to diseases. We report integrated analyses of 3D genome alterations and differential gene expressions in 18 newly diagnosed T-lineage acute lymphoblastic leukemia (T-ALL) patients and 4 healthy controls. 3D genome organizations at the levels of compartment, topologically associated domains and loop could hierarchically classify different subtypes of T-ALL according to T cell differentiation trajectory, similar to gene expressions-based classification. Thirty-four previously unrecognized translocations and 44 translocation-mediated neo-loops are mapped by Hi-C analysis. We find that neo-loops formed in the non-coding region of the genome could potentially regulate ectopic expressions of TLX3, TAL2 and HOXA transcription factors via enhancer hijacking. Importantly, both translocation-mediated neo-loops and NUP98-related fusions are associated with HOXA13 ectopic expressions. Patients with HOXA11-A13 expressions, but not other genes in the HOXA cluster, have immature immunophenotype and poor outcomes. Here, we highlight the potentially important roles of 3D genome alterations in the etiology and prognosis of T-ALL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-24044-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211852PMC
June 2021

Effect of chlorhexidine-loaded poly(amido amine) dendrimer on matrix metalloproteinase activities and remineralization in etched human dentin in vitro.

J Mech Behav Biomed Mater 2021 09 10;121:104625. Epub 2021 Jun 10.

Stomatological Hospital of Chongqing Medical University, Chongqing, 401147, China. Electronic address:

To investigate the effect of chlorhexidine (CHX)-loaded carboxyl-terminated poly (amido amine) dendrimer (CHX-PAMAM-COOH) on matrix metalloproteinase (MMP) activities and remineralization in human dentin, CHX-PAMAM-COOH was prepared and characterized by Fourier-transform infrared spectroscopy. The inhibitory effects of CHX, PAMAM-COOH, and CHX-PAMAM-COOH on soluble recombinant human matrix metalloproteinase (rhMMP-2) and dentin-bound endogenous MMP activity were measured using an MMP Activity Assay Kit. In situ zymography was performed to evaluate the gelatinase activity in dentin pretreated with CHX, PAMAM-COOH, and CHX-PAMAM-COOH. The remineralization of etched dentin pretreated with CHX, PAMAM-COOH, and CHX-PAMAM-COOH was evaluated by field emission-scanning electron microscopy (SEM) and energy disperse spectroscopy (EDS) after incubation in artificial saliva for 14 days. The results of the rhMMP-2 activity assay showed that the MMP-2 activity in the CHX-PAMAM-COOH group and the CHX group decreased significantly to 5.58 ± 0.85% (P < 0.05) and 4.86 ± 1.12% (P < 0.05), respectively, but that in the PAMAM-COOH group increased significantly to 213.38 ± 0.11% (P < 0.05). The results of total MMP activity and in situ zymography showed a significant reduction in endogenous gelatinase activity in dentin in the CHX-PAMAM-COOH group and the CHX group. The SEM and EDS results showed that rod-like crystals were formed on the etched dentin surface in the PAMAM-COOH group and the CHX-PAMAM-COOH group, and their Ca/P ratios were 1.73 and 1.71, respectively. In conclusion, CHX-PAMAM-COOH can inhibit dentin-bound endogenous MMPs and induce remineralization in etched dentin simultaneously. However, it is important to note that the catalytic role of PAMAM dendrimers may have an undesired excitatory effect on MMP activity, which cannot be ignored if PAMAM dendrimers were used alone in the oral environment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmbbm.2021.104625DOI Listing
September 2021

An integrated gene catalog and over 10,000 metagenome-assembled genomes from the gastrointestinal microbiome of ruminants.

Microbiome 2021 06 12;9(1):137. Epub 2021 Jun 12.

Laboratory of Gastrointestinal Microbiology, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China.

Background: Gastrointestinal tract (GIT) microbiomes in ruminants play major roles in host health and thus animal production. However, we lack an integrated understanding of microbial community structure and function as prior studies. are predominantly biased towards the rumen. Therefore, to acquire a microbiota inventory of the discrete GIT compartments, In this study, we used shotgun metagenomics to profile the microbiota of 370 samples that represent 10 GIT regions of seven ruminant species.

Results: Our analyses reconstructed a GIT microbial reference catalog with > 154 million nonredundant genes and identified 8745 uncultured candidate species from over 10,000 metagenome-assembled genomes. The integrated gene catalog across the GIT regions demonstrates spatial associations between the microbiome and physiological adaptations, and 8745 newly characterized genomes substantially expand the genomic landscape of ruminant microbiota, particularly those from the lower gut. This substantially expands the previously known set of endogenous microbial diversity and the taxonomic classification rate of the GIT microbiome. These candidate species encode hundreds of enzymes and novel biosynthetic gene clusters that improve our understanding concerning methane production and feed efficiency in ruminants. Overall, this study expands the characterization of the ruminant GIT microbiota at unprecedented spatial resolution and offers clues for improving ruminant livestock production in the future.

Conclusions: Having access to a comprehensive gene catalog and collections of microbial genomes provides the ability to perform efficiently genome-based analysis to achieve a detailed classification of GIT microbial ecosystem composition. Our study will bring unprecedented power in future association studies to investigate the impact of the GIT microbiota in ruminant health and production. Video abstract.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40168-021-01078-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199421PMC
June 2021

Variables associated with patient-reported outcomes in patients with myeloproliferative neoplasms.

Leuk Lymphoma 2021 Jun 8:1-13. Epub 2021 Jun 8.

Peking University People's Hospital, Beijing, China.

We explored variables associated with patient-reported outcomes (PROs) including symptom burden, impact on daily life and work, obstacles during therapy, satisfaction level with therapy, and health-related quality of life in 1500 respondents with myeloproliferative neoplasms (MPNs) including essential thrombocythemia (ET), polycythemia vera (PV) and myelofibrosis (MF) in a multicenter, cross-sectional study across China, a representative of the developing countries. In multivariate analyses, urban household registration and higher education level were significantly-associated with no symptoms at diagnosis in respondents with ET or MF. mutation was significantly-associated with lower MPN-10 scores in respondents with MF. Higher MPN-10 scores were significantly-associated with negative impact on daily life and work as well as lower satisfaction level in respondents with ET, PV and MF. Receiving ruxolitinib was significantly-associated with high satisfaction and satisfaction in respondents with MF. In addition, other demographics and clinical variables were also impacting PROs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10428194.2021.1933481DOI Listing
June 2021
-->