Publications by authors named "Feng Qiao"

102 Publications

Ipomoea staphylina Attenuates Potassium Dichromate-Induced Nephrotoxicity in Wistar Rats via Antioxidant and Antiapoptotic Effects.

Dokl Biochem Biophys 2021 Jul 23;499(1):289-295. Epub 2021 Aug 23.

Department of Nephrology, Chengdu Fifth People's Hospital, 611130, Chengdu, Sichuan, China.

Occupational and environmental exposure to chromium compounds leads to nephrotoxicity to humans and animals due to the overproduction of ROS. Our study was aimed to demonstrate the shielding effect of hydroethanolic extract of Ipomoea staphylina (HEIS) bark on male Wistar rats challenged with potassium dichromate (KCrO). Division of animals was done in 4 groups' viz., normal control, KCrO control, KCrO+HEIS (100 mg/kg), and KCrO+HEIS (200 mg/kg). Except for the normal control group, other groups were challenged with a single dose (subcutaneous) of KCrO (15 mg/kg) and then treated with HEIS (100 and 200 mg/kg) for 1 week. It was observed that animals treated with KCrO showed a notable increase in serum creatinine, blood urea, and BUN and dwindles in protein level. These changes were significantly reversed after a 1-week treatment with HEIS (100 and 200 mg/kg). Moreover, HEIS (100 and 200 mg/kg) showed a remarkable improvement in the activity of antioxidant enzymes (GPx, CAT, and SOD) and decreased the levels of TNF-α and IL-1β in the kidney. Furthermore, treatment with HEIS (100 and 200 mg/kg) notably decreased the activity of caspase-3 and improved the level of HO-1 especially in the KCrO+ HEIS (200 mg/kg) group. Also, the histopathological study of the kidney supported the protective effects of HEIS. Hence, HEIS bark holds a notable protective effect against KCrO-induced nephrotoxicity in rats.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1134/S1607672921040074DOI Listing
July 2021

Clustering of genes from microarray data using hierarchical projective adaptive resonance theory: a case study of tuberculosis.

Brief Funct Genomics 2021 Aug 9. Epub 2021 Aug 9.

School of Mathematics and Statistics, Southwest University, Chongqing, China.

We propose the hierarchical Projective Adaptive Resonance Theory (PART) algorithm for classification of gene expression data. This algorithm is realized by combing transposed quasi-supervised PART and unsupervised PART. We develop the corresponding validation statistics for each process and compare it with other clustering algorithms in a case study of tuberculosis (TB). First, we use sample-based transposed quasi-supervised PART to obtain optimal clustering results of samples distinguished by time post-infection and the representative genes for each cluster including up-regulated, down-regulated and stable genes. The up- and down-regulated genes show more than 90% similarity to the result derived from Linear Models for Microarray Data and are verified by weighted k-nearest neighbor model on TB projection. Second, we use gene-based unsupervised PART algorithm to cluster these representative genes where functional enrichment analysis is conducted in each cluster. We further confirm the main immune response of human macrophage-like THP-1 cells against TB within 2 days is type I interferon-mediated innate immunity. This study demonstrates how hierarchical PART algorithm analyzes microarray data. The sample-based quasi-supervised PART extracts representative genes and narrows down the shortlist of disease-relevant genes and gene-based unsupervised PART classifies representative genes that help to interpret immune response against TB.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/bfgp/elab034DOI Listing
August 2021

Ketogenesis impact on liver metabolism revealed by proteomics of lysine β-hydroxybutyrylation.

Cell Rep 2021 Aug;36(5):109487

Center for Epigenetics and Metabolism, U1233 INSERM, Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA.

Ketone bodies are bioactive metabolites that function as energy substrates, signaling molecules, and regulators of histone modifications. β-hydroxybutyrate (β-OHB) is utilized in lysine β-hydroxybutyrylation (Kbhb) of histones, and associates with starvation-responsive genes, effectively coupling ketogenic metabolism with gene expression. The emerging diversity of the lysine acylation landscape prompted us to investigate the full proteomic impact of Kbhb. Global protein Kbhb is induced in a tissue-specific manner by a variety of interventions that evoke β-OHB. Mass spectrometry analysis of the β-hydroxybutyrylome in mouse liver revealed 891 sites of Kbhb within 267 proteins enriched for fatty acid, amino acid, detoxification, and one-carbon metabolic pathways. Kbhb inhibits S-adenosyl-L-homocysteine hydrolase (AHCY), a rate-limiting enzyme of the methionine cycle, in parallel with altered metabolite levels. Our results illuminate the role of Kbhb in hepatic metabolism under ketogenic conditions and demonstrate a functional consequence of this modification on a central metabolic enzyme.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.celrep.2021.109487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8372761PMC
August 2021

The cooperative assembly of shelterin bridge provides a kinetic gateway that controls telomere length homeostasis.

Nucleic Acids Res 2021 Aug;49(14):8110-8119

Department of Biological Chemistry, School of Medicine, University of California, Irvine, CA 92697-1700, USA.

Shelterin is a six-protein complex that coats chromosome ends to ensure their proper protection and maintenance. Similar to the human shelterin, fission yeast shelterin is composed of telomeric double- and single-stranded DNA-binding proteins, Taz1 and Pot1, respectively, bridged by Rap1, Poz1 and Tpz1. The assembly of the proteinaceous Tpz1-Poz1-Rap1 complex occurs cooperatively and disruption of this shelterin bridge leads to unregulated telomere elongation. However, how this biophysical property of bridge assembly is integrated into shelterin function is not known. Here, utilizing synthetic bridges with a range of binding properties, we find that synthetic shelterin bridge lacking cooperativity requires a linker pair that matches the native bridge in complex lifespan but has dramatically higher affinity. We find that cooperative assembly confers kinetic properties on the shelterin bridge allowing disassembly to function as a molecular timer, regulating the duration of the telomere open state, and consequently telomere lengthening to achieve a defined species-specific length range.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/nar/gkab550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373121PMC
August 2021

Relationship between the difference in electric pulp test values and the diagnostic type of pulpitis.

BMC Oral Health 2021 07 10;21(1):339. Epub 2021 Jul 10.

Department of Endodontics, School of Stomatology, Tianjin Medical University, #12 Qi Xiang Tai Road, He Ping District, Tianjin, 300070, China.

Background: According to the diagnosis criteria of the American Association of Endodontists (AAE), sensitive responses to cold and/or heat tests of suspected teeth compared with those of control teeth can be used for the diagnosis of pulpitis, but the role of electric pulp test (EPT) is not mentioned. It is believed that EPT has some limitations in determining the vitality of the pulp. The aim of this study was to explore the association between the difference in EPT values and the differential diagnoses of reversible pulpitis (RP) and symptomatic irreversible pulpitis (SIRP) caused by dental caries.

Methods: A total of 203 cases with pulpitis caused by dental caries were included. A diagnosis of pulpitis was made on the basis of the diagnostic criteria of AAE. Patient demographic and clinical examination data were collected. The EPT values of the suspected teeth and control teeth were measured, and the differences between them were calculated. The correlation between the difference in the EPT values and diagnosis of pulpitis was analyzed using univariate and multivariate logistic regression.

Results: In the 203 cases (78 males and 125 females; 115 cases of RP, 88 cases of SIRP; 9 anterior teeth, 59 premolars, and 135 molars), the mean patient age was 34.04 ± 13.02 (standard deviation) years. The unadjusted (crude) model, model 1 (adjusted for age), model 2 (adjusted for age and sex), and model 3 (adjusted for age, sex, and tooth type) were established for the statistical analyses. In model 3 [odds ratio (OR) = 1.025; 95% confidence interval (CI) 1.002-1.050; P = 0.035], the difference in EPT values between RP and SIRP was statistically significant. However, the areas under the curve of predictive probability of the crude model, model 1, model 2, and model 3 were 0.565, 0.570, 0.585, and 0.617, respectively, showing that the model accuracy was low. The P-value for the trend in differences between the EPT values as a categorical variable showed that the differences in the EPT values, comparing RP and SIRP, were not statistically significant.

Conclusions: Based on the present data, the difference in EPT values was not sufficient to differentiate RP from SIRP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12903-021-01696-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8272274PMC
July 2021

The histone H3K9M mutation synergizes with H3K14 ubiquitylation to selectively sequester histone H3K9 methyltransferase Clr4 at heterochromatin.

Cell Rep 2021 May;35(7):109137

Department of Biological Sciences, Columbia University, New York, NY 10027, USA. Electronic address:

Oncogenic histone lysine-to-methionine mutations block the methylation of their corresponding lysine residues on wild-type histones. One attractive model is that these mutations sequester histone methyltransferases, but genome-wide studies show that mutant histones and histone methyltransferases often do not colocalize. Using chromatin immunoprecipitation sequencing (ChIP-seq), here, we show that, in fission yeast, even though H3K9M-containing nucleosomes are broadly distributed across the genome, the histone H3K9 methyltransferase Clr4 is mainly sequestered at pericentric repeats. This selective sequestration of Clr4 depends not only on H3K9M but also on H3K14 ubiquitylation (H3K14ub), a modification deposited by a Clr4-associated E3 ubiquitin ligase complex. In vitro, H3K14ub synergizes with H3K9M to interact with Clr4 and potentiates the inhibitory effects of H3K9M on Clr4 enzymatic activity. Moreover, binding kinetics show that H3K14ub overcomes the Clr4 aversion to H3K9M and reduces its dissociation. The selective sequestration model reconciles previous discrepancies and demonstrates the importance of protein-interaction kinetics in regulating biological processes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.celrep.2021.109137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167812PMC
May 2021

Image-Guided Human Reconstruction via Multi-Scale Graph Transformation Networks.

IEEE Trans Image Process 2021 25;30:5239-5251. Epub 2021 May 25.

3D human reconstruction from a single image is a challenging problem. Existing methods have difficulties to infer 3D clothed human models with consistent topologies for various poses. In this paper, we propose an efficient and effective method using a hierarchical graph transformation network. To deal with large deformations and avoid distorted geometries, rather than using Euclidean coordinates directly, 3D human shapes are represented by a vertex-based deformation representation that effectively encodes the deformation and copes well with large deformations. To infer a 3D human mesh consistent with the input real image, we also use a perspective projection layer to incorporate perceptual image features into the deformation representation. Our model is easy to train and fast to converge with short test time. Besides, we present the DHuman (Dynamic Detailed Human) dataset, including variously posed 3D human meshes with consistent topologies and rich geometry details, together with the captured color images and SMPL models, which is useful for training and evaluation of deep frameworks, particularly for graph neural networks. Experimental results demonstrate that our method achieves more plausible and complete 3D human reconstruction from a single image, compared with several state-of-the-art methods. The code and dataset are available for research purposes at http://cic.tju.edu.cn/faculty/likun/projects/MGTnet.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/TIP.2021.3080177DOI Listing
May 2021

Spatio-temporal landscape of mouse epididymal cells and specific mitochondria-rich segments defined by large-scale single-cell RNA-seq.

Cell Discov 2021 May 18;7(1):34. Epub 2021 May 18.

Institute of Reproductive Medicine, Medical School of Nantong University, Nantong, Jiangsu 226019, China.

Spermatozoa acquire their fertilizing ability and forward motility during epididymal transit, suggesting the importance of the epididymis. Although the cell atlas of the epididymis was reported recently, the heterogeneity of the cells and the gene expression profile in the epididymal tube are still largely unknown. Considering single-cell RNA sequencing results, we thoroughly studied the cell composition, spatio-temporal differences in differentially expressed genes (DEGs) in epididymal segments and mitochondria throughout the epididymis with sufficient cell numbers. In total, 40,623 cells were detected and further clustered into 8 identified cell populations. Focused analyses revealed the subpopulations of principal cells, basal cells, clear/narrow cells, and halo/T cells. Notably, two subtypes of principal cells, the Prc7 and Prc8 subpopulations were enriched as stereocilia-like cells according to GO analysis. Further analysis demonstrated the spatially specific pattern of the DEGs in each cell cluster. Unexpectedly, the abundance of mitochondria and mitochondrial transcription (MT) was found to be higher in the corpus and cauda epididymis than in the caput epididymis by scRNA-seq, immunostaining, and qPCR validation. In addition, the spatio-temporal profile of the DEGs from the P42 and P56 epididymis, including transiting spermatozoa, was depicted. Overall, our study presented the single-cell transcriptome atlas of the mouse epididymis and revealed the novel distribution pattern of mitochondria and key genes that may be linked to sperm functionalities in the first wave and subsequent wave of sperm, providing a roadmap to be emulated in efforts to achieve sperm maturation regulation in the epididymis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41421-021-00260-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129088PMC
May 2021

The genetic mechanism of heterosis utilization in maize improvement.

Genome Biol 2021 05 10;22(1):148. Epub 2021 May 10.

National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan, 430070, China.

Background: In maize hybrid breeding, complementary pools of parental lines with reshuffled genetic variants are established for superior hybrid performance. To comprehensively decipher the genetics of heterosis, we present a new design of multiple linked F1 populations with 42,840 F1 maize hybrids, generated by crossing a synthetic population of 1428 maternal lines with 30 elite testers from diverse genetic backgrounds and phenotyped for agronomic traits.

Results: We show that, although yield heterosis is correlated with the widespread, minor-effect epistatic QTLs, it may be resulted from a few major-effect additive and dominant QTLs in early developmental stages. Floral transition is probably one critical stage for heterosis formation, in which epistatic QTLs are activated by paternal contributions of alleles that counteract the recessive, deleterious maternal alleles. These deleterious alleles, while rare, epistatically repress other favorable QTLs. We demonstrate this with one example, showing that Brachytic2 represses the Ubiquitin3 locus in the maternal lines; in hybrids, the paternal allele alleviates this repression, which in turn recovers the height of the plant and enhances the weight of the ear. Finally, we propose a molecular design breeding by manipulating key genes underlying the transition from vegetative-to-reproductive growth.

Conclusion: The new population design is used to dissect the genetic basis of heterosis which accelerates maize molecular design breeding by diminishing deleterious epistatic interactions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13059-021-02370-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8108465PMC
May 2021

CTRP9 protects against MIA-induced inflammation and knee cartilage damage by deactivating the MAPK/NF-κB pathway in rats with osteoarthritis.

Open Life Sci 2020 23;15(1):971-980. Epub 2020 Dec 23.

Department of Integrated TCM & Western Medicine Orthopaedics, Xi'an Honghui Hospital, Xi'an Jiaotong University, 555 of Youyi East Road, Xi'an 710056, China.

C1q/TNF-related protein 9 (CTRP9), the closest paralog of adiponectin, has been reported to protect against inflammation-related diseases. However, its role in regulating osteoarthritis (OA) has not been fully elucidated. First, a rat model of OA was generated. Furthermore, rats with OA were injected with different doses of recombinant CTRP9 protein (rCTRP9), and the knee cartilage damage was evaluated. Finally, the phosphorylation of p38 and the secretion of matrix metalloproteinases (MMPs) were detected by Western blotting and enzyme-linked immunosorbent assay. Results revealed that CTRP9 was highly expressed in adipose tissue, followed by skeletal muscle and cartilage tissue, and less expressed in liver, kidney and lung. Moreover, the expression of CTRP9 significantly decreased in the monosodium iodoacetate (MIA) group in the knee cartilage and knee synovial fluid, and the contents of interleukin-1β (IL-1β) and IL-6 significantly increased in knee synovial fluid. In addition, rCTRP9 alleviated MIA-induced inflammation, oxidative stress and knee cartilage damage in a dose-dependent way. In addition, rCTRP9 could attenuate the expression of p38MAPK and p-p38 and suppress the expression of nuclear factor-kappa B (NF-κB), p65 and MMPs. Collectively, the results of the present study suggested that CTRP9 alleviates the inflammation of MIA-induced OA through deactivating p38MAPK and NF-κB signaling pathways in rats.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1515/biol-2020-0105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874593PMC
December 2020

Triptolide laden reduced graphene oxide transdermal hydrogel to manage knee arthritis: and studies.

J Biomater Sci Polym Ed 2021 Jul 18;32(10):1288-1300. Epub 2021 May 18.

Department of Orthopedics combined TCM with Western Medicine, Honghui Hospital, Xi'an Jiaotong University, No. 555 Youyi East Road, Beilin, Xi'an, Shaanxi, 710054, China.

Triptolide (extract of herb ) is widely used in rheumatoid arthritis due to its potent immunosuppressant effect. The marketed oral (tablet dosage forms) and parenteral injections have short duration of action (half-life = 38 min) and not limited to multiorgan toxicity, which restrict the use of triptolide in clinical practice. In this study, a triptolide-loaded Pluronic® F68-reduced graphene oxide transdermal (non-invasive) hydrogel was developed to achieve sustained release of triptolide. Fourier transform infrared spectroscopy, X-ray diffraction, and Raman spectroscopy confirmed the synthesis of Pluronic F68-reduced graphene oxide. Transmission electron microscopy showed flat wrinkled-nanosheets. The developed hydrogel showed desirable viscosity (11,261-11,365 cps), adhesiveness (0.25 mJ), hardness (6.5 g), and cohesiveness (1.85) for transdermal application. The release study demonstrated the ability of the Pluronic F68-reduced graphene oxide hydrogel to prolong release up to 14 h (63.64-96.78%), owing to the strong π-π interactions between the graphene oxide and the triptolide. The pharmacokinetic parameters in the rat model confirmed the improvement in the relative bioavailability (3.3-fold) with Pluronic F68-reduced graphene oxide hydrogel in comparison to the control hydrogel without reduced graphene oxide. The anti-rheumatoid efficacy model suggest the potential application of Pluronic F68-reduced graphene oxide hydrogel to treat knee rheumatoid arthritis (70-75% resolution) to substitute tablets and parenteral injections.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/09205063.2021.1912976DOI Listing
July 2021

Effects of different prosthetic instrumentations on tibial bone resection in total knee arthroplasty.

Sci Rep 2021 Mar 31;11(1):7297. Epub 2021 Mar 31.

Osteonecrosis and Joint Reconstruction Ward, Department of Joint Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, 710054, Shaanxi, People's Republic of China.

Our aim was to assess the accuracy of the obtained posterior tibial slope (PTS) with a fixed angle cutting block. 247 TKAs in 213 patients were reviewed. We included 104 Legion Prosthesis, 76 U2 Knee Prosthesis, 46 NexGen LPS-Flex Prosthesis, and 21 Vanguard Knee System products. Preoperative and postoperative PTS were measured via expanded lateral tibia radiographs. For postoperative PTS, the Legion group had significantly smaller slopes than the U2 Knee group and Vanguard group. However, there was no significant difference between the Legion and NexGen groups, and no significant difference among the NexGen, U2 Knee, and Vanguard groups. Multiple linear regression showed that the different tibial lengths and preoperative PTS had statistically significant effects on postoperative PTS. However, there were weak correlations between the tibial length and PTS, and between preoperative and postoperative PTS. For TKA, although the PTS is not completely consistent with the angle of the cutting block, using conventional tibial bone resection technology with different tibial cutting instrumentations provided by various manufacturers in TKA can obtain safe PTS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-86787-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012597PMC
March 2021

Operation time is independent associated with serious postoperative symptom in patients with mandibular third molar removal.

Ann Palliat Med 2021 Apr 12;10(4):4080-4089. Epub 2021 Mar 12.

Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Tianjin Medical University, Tianjin, China.

Background: To investigate the association between operation time and serious postoperative symptom severity (PoSS) in patients following the surgical removal of mandibular third molar (M3M), independent of the degree of impaction.

Methods: A retrospective hospital-based observational study was carried out at the Stomatology Hospital of Tianjin Medical University. The operation time was recorded and divided by quartiles (Q1-Q4). The primary outcome was PoSS. Clinical, demographic and radiologic variables were also recorded. A descriptive bivariate analysis was performed. Associations were analyzed using the adjusted multivariate logistic regression. The association between time and impaction status was also tested. Potential nonlinear associations were evaluated with the restricted cubic spline. P values of <0.05 were considered as statistically significant.

Results: A total of 321 patients met our inclusion criteria (114 men and 207 women). The mean operation time was 16.0 minutes (range, 1.1 to 40.5 minutes). The odds ratio (OR) and 95% confidence interval (CI) were determined after multivariate adjustments for the risk of serious PoSS per 5-min incremental increase in operation time (OR 1.201, 95% CI, 1.005-1.434). The multivariable-adjusted ORs (95% CI) of PoSS across the categories of operation time were as follows: 1.00 (reference), 1.765 (0.770-4.045), 2.567 (1.047-6.293), and 3.085 (1.180-8.064) (P for trend =0.027). The test of interaction effect was not significant (all P for interaction >0.05). No evidence of a nonlinear association was observed (P for nonlinearity =0.117).

Conclusions: Operation time was significantly and positively associated with a high risk of serious PoSS independent of impaction status in patients who underwent the surgical removal of M3M.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/apm-20-2340DOI Listing
April 2021

Analysis of the cytotoxic effects, cellular uptake and cellular distribution of paclitaxel-loaded nanoparticles in glioblastoma cells .

Exp Ther Med 2021 Apr 27;21(4):292. Epub 2021 Jan 27.

Department of Pathology and Physiology, School of Basic Medical Sciences of Jiamusi University, Jiamusi, Heilongjiang 154007, P.R. China.

Glioblastoma is the most common and aggressive type of brain tumor. Although treatments for glioblastoma have been improved recently, patients still suffer from local recurrence in addition to poor prognosis. Previous studies have indicated that the efficacy of chemotherapeutic or bioactive agents is severely compromised by the blood-brain barrier and the inherent drug resistance of glioblastoma. The present study developed a delivery system to improve the efficiency of delivering therapeutic agents into glioblastoma cells. The anticancer drug paclitaxel (PTX) was packed into nanoparticles that were composed of amphiphilic poly (γ-glutamic-acid-maleimide-co-L-lactide)-1,2-dipalmitoylsn-glycero-3-phosphoethanolaminecopolymer conjugated with targeting moiety transferrin (Tf). The Tf nanoparticles (Tf-NPs) may enter glioblastoma cells via transferrin receptor-mediated endocytosis. MTT assay and flow cytometry were used to explore the cytotoxic effects, cellular uptake and cellular distribution of paclitaxel-loaded nanoparticles. The results indicated that both PTX and PTX-Tf-NPs inhibited the viability of rat glioblastoma C6 cells in a dose-dependent manner, but the PTX-Tf-NPs exhibited a greater inhibitory effect compared with PTX, even at higher concentrations (0.4, 2 and 10 µg/ml). However, both PTX and PTX-Tf-NPs exhibited a reduced inhibitory effect on the viability of mouse hippocampal neuronal HT22 cells compared with that on C6 cells. Additionally, in contrast to PTX alone, PTX-Tf-NPs treatment of C6 cells at lower concentrations (0.0032, 0.0160 and 0.0800 µg/ml) induced increased G/M arrest, although this difference did not occur at a higher drug concentration (0.4 µg/ml). It was observed that FITC-labeled PTX-Tf-NPs were endocytosed by C6 cells within 4 h. Furthermore, FITC-labeled PTX-Tf-NPs or Tf-NPs co-localized with a lysosomal tracker, Lysotracker Red DND-99. These results of the present study indicated that Tf-NPs enhanced the cytotoxicity of PTX in glioblastoma C6 cells, suggesting that PTX-Tf-NPs should be further explored in animal models of glioblastoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/etm.2021.9723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885080PMC
April 2021

[Finite element analysis on stress concentration improvement in patellofemoral joint by releasing lateral patellar retinaculum with stiletto needle based on the theory of Jinshugu()].

Zhongguo Gu Shang 2021 Feb;34(2):126-30

Department of Orthopaedics, Wangjing Hospital of China Academy of Chinese Medicine, Beijing 100102, China.

Objective: To study mechanism of improvement of stress concentration on patellofemoral joint by stiletto needle releasing lateral patellar retinaculum guided by the theory of Jinshugu() and based on the finite element model of knee joint. and to elucidate the biomechanical mechanism of stiletto needle releasing changing patellar trajectory and reducing patellofemoral joint pressure.

Methods: CT data of knee joint from a normal male (aged 29, heighted 171 cm, weighted 58 kg) was selected. Starting with construction of three-dimensional model of knee joint by using finite element software, the finite element model of knee joint with complete tendonand bone structures were established through several steps, such as geometric reconstruction, reverse engineering, meshing, material assignment and loading analysis. The loading condition was set as 500 N load on knee joint, and the average tensile stress of quadriceps femoris tendon was about 200 N. To simulate the release of lateral patellar retinaculum by stiletto needle at 30 and 90 position of knee flexion in finite element model separately, and to compare the improvement of stress concentration of patellofemoral joint by stiletto needle intervention under different knee flexion conditions.

Results: The peak stress of patellofemoral joint and tibiofemoral joint decreased after stiletto needle releasing of patellofemoral lateral retinaculum compared with before intervention, which was(1) knee flexion at 30 degrees:patellar cartilage decreased by 0.498 MPa (decreased 9.06%), femoral trochlea decreased by 0.886 MPa(decreased 16.27%);(2) knee flexion at 90 degrees:patellar cartilage decreased by 0.558 MPa (decreased 8.6%), femoral trochlea decreasedby 0.607 MPa (decreased 9.94%).

Conclusion: Releasing lateral patellofemoral retinaculum with stiletto needle could effectively alleviate the stress concentration of patellofemoral joint and reduce local stress peak value, which it is helpful to improve patellar trajectory and make stress distribution more uniform.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12200/j.issn.1003-0034.2021.02.006DOI Listing
February 2021

Association of Overlapped and Un-overlapped Comorbidities with COVID-19 Severity and Treatment Outcomes: A Retrospective Cohort Study from Nine Provinces in China.

Biomed Environ Sci 2020 Dec;33(12):893-905

Department of Traditional Chinese Medicine, The First Hospital of Suihua City, Suihua 152053, Heilongjiang, China.

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear.

Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( ) and 95% confidence interval (95% ) of the associations between comorbidities (cardiometabolic or non-cardiometabolic diseases), clinical severity, and treatment outcomes of COVID-19.

Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks.

Conclusion: Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3967/bes2020.123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817475PMC
December 2020

Polymeric non-spherical coarse microparticles fabricated by double emulsion-solvent evaporation for simvastatin delivery.

Colloids Surf B Biointerfaces 2021 Mar 6;199:111560. Epub 2021 Jan 6.

Biomedical Barriers Research Center, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Biomedical Materials, Tianjin, 300192, China. Electronic address:

Polymeric particles with non-spherical shape or coarse surface have distinct advantages for drug delivery, tissue regeneration and immunomodulation respectively, but it is not easy to control polymeric microparticles in required geometry and surface texture simultaneously. In this study, polymeric non-spherical microparticles with coarse surface were successfully prepared by double emulsion-solvent evaporation technique in the presence of ammonium bicarbonate and the formation mechanism was proposed. In addition, simvastatin was encapsulated in poly[lactic-co-(glycolic acid)] (PLGA) non-spherical microparticles with coarse surface by the same technique and the release kinetics in vitro was fitted as well, which not only enrich the encapsulation techniques of liposoluble drugs in polymeric non-spherical carriers but also envision the potential application for alveolar ridge preservation with local delivery of simvastatin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.colsurfb.2021.111560DOI Listing
March 2021

Quality-Control Mechanism for Telomerase RNA Folding in the Cell.

Cell Rep 2020 12;33(13):108568

Department of Biological Chemistry, School of Medicine, University of California, Irvine, CA 92697-1700, USA. Electronic address:

Long non-coding RNAs can often fold into different conformations. Telomerase RNA, an essential component of the telomerase ribonucleoprotein (RNP) enzyme, must fold into a defined structure to fulfill its function with the protein catalytic subunit (TERT) and other accessory factors. However, the mechanism by which the correct folding of telomerase RNA is warranted in a cell is still unknown. Here we show that La-related protein Pof8 specifically recognizes the conserved pseudoknot region of telomerase RNA and instructs the binding of the Lsm2-8 complex to its mature 3' end, thus selectively protecting the correctly folded RNA from exonucleolytic degradation. In the absence of Pof8, TERT assembles with misfolded RNA and produces little telomerase activity. Therefore, Pof8 plays a key role in telomerase RNA folding quality control, ensuring that TERT only assembles with functional telomerase RNA to form active telomerase. Our finding reveals a mechanism for non-coding RNA folding quality control.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.celrep.2020.108568DOI Listing
December 2020

Association between early treatment with Qingfei Paidu decoction and favorable clinical outcomes in patients with COVID-19: A retrospective multicenter cohort study.

Pharmacol Res 2020 11 9;161:105290. Epub 2020 Nov 9.

China Academy of Chinese Medical Sciences, Beijing, China.

The coronavirus disease 2019 (COVID-19) epidemic has been almost controlled in China under a series of policies, including "early diagnosis and early treatment". This study aimed to explore the association between early treatment with Qingfei Paidu decoction (QFPDD) and favorable clinical outcomes. In this retrospective multicenter study, we included 782 patients (males, 56 %; median age 46) with confirmed COVID-19 from 54 hospitals in nine provinces of China, who were divided into four groups according to the treatment initiation time from the first date of onset of symptoms to the date of starting treatment with QFPDD. The primary outcome was time to recovery; days of viral shedding, duration of hospital stay, and course of the disease were also analyzed. Compared with treatment initiated after 3 weeks, early treatment with QFPDD after less than 1 week, 1-2 weeks, or 2-3 weeks had a higher likelihood of recovery, with adjusted hazard ratio (HR) (95 % confidence interval [CI]) of 3.81 (2.65-5.48), 2.63 (1.86-3.73), and 1.92 (1.34-2.75), respectively. The median course of the disease decreased from 34 days to 24 days, 21 days, and 18 days when treatment was administered early by a week (P < 0.0001). Treatment within a week was related to a decrease by 1-4 days in the median duration of hospital stay compared with late treatment (P<0.0001). In conclusion, early treatment with QFPDD may serve as an effective strategy in controlling the epidemic, as early treatment with QFPDD was associated with favorable outcomes, including faster recovery, shorter time to viral shedding, and a shorter duration of hospital stay. However, further multicenter, prospective studies with a larger sample size should be conducted to confirm the benefits of early treatment with QFPDD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phrs.2020.105290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833425PMC
November 2020

Truncated HDAC9 identified by integrated genome-wide screen as the key modulator for paclitaxel resistance in triple-negative breast cancer.

Theranostics 2020 2;10(24):11092-11109. Epub 2020 Sep 2.

Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.

Paclitaxel resistance is a major concern when treating triple-negative breast cancer (TNBC) patients. We aimed to identify candidates causing paclitaxel resistance and explore their significance in TNBC therapeutics. A genome-wide CRISPR screening, integrated with transcriptome analyses, was performed to identify candidates involved in paclitaxel-resistant TNBCs. Cell proliferation, cytotoxicity, immunofluorescent staining, and xenograft assays were conducted to verify the phenotypes of paclitaxel resistance induced by candidate genes, both and . RNA sequencing, Western blotting, and chromatin immunoprecipitation assays were used to explore the underlying mechanisms. MEF2-interacting transcriptional repressor (MITR), the truncated isoform of histone deacetylase 9 (HDAC9) lacking the deacetylation domain, was enriched in paclitaxel-resistant cells. Elevated MITR expression resulted in increased interleukin-11 (IL11) expression and activation of downstream JAK/STAT3 signaling. Mechanistically, MITR counteracted MEF2A-induced transcriptional suppression of IL11, ultimately causing paclitaxel resistance. By contrast, pharmacological inhibition of JAK1/2 by ruxolitinib reversed paclitaxel resistance both and . Our and genetic and cellular analyses elucidated the pivotal role of MITR/MEF2A/IL11 axis in paclitaxel resistance and provided a novel therapeutic strategy for TNBC patients to overcome poor chemotherapy responses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/thno.44997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532680PMC
May 2021

Establishment and validation of a predictive nomogram for extended operation time following mandibular third molar removal.

Clin Oral Investig 2021 Apr 10;25(4):1915-1923. Epub 2020 Aug 10.

Department of Oral Preventive Medicine, School and Hospital of Stomatology, Tianjin Medical University, Tianjin, China.

Objectives: To develop and evaluate predictive nomogram for extended duration of surgery in patients following mandibular third molars (M3M) removal.

Materials And Methods: A retrospectively observational study was performed and designed. A credible random split-sample method was used to divide data into training and validation dataset (split ratio = 0.7:0.3). Least absolute shrinkage and selection operator (Lasso) logistic regression was applied to select predictors and develop the nomogram. The discrimination of the nomogram was assessed using the receiver operating characteristic (ROC) curve, and the calibration curve was used for evaluating the accuracy of prediction. The clinical usefulness of nomogram was also evaluated with decision curve analysis.

Results: Root of curve, Winter classification, Pell-Gregory ramus classification, flap design, procedure, and surgical experience were identified as predictors and assembled into the nomogram. The nomogram showed good discrimination with AUC in training dataset (0.79, 95% CI: 0.73-0.85) and validation dataset (0.75, 95% CI: 0.65-0.84) and was well calibrated in both datasets (all P > 0.05). Decision curve analysis demonstrated that the nomogram was clinically useful.

Conclusions: This study proposed an effective nomogram with potentially application in facilitating the individualized prediction for extended operation time.

Clinical Relevance: Individualized prediction of prolonged operation time can be conveniently facilitating an adequate treatment plan management and postoperative prevention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00784-020-03499-8DOI Listing
April 2021

Dual-Tracer Assessment of Dynamic Changes in Reoxygenation and Proliferation Decrease During Fractionated Radiotherapy in Murine Tumors.

Front Oncol 2020 17;10:1046. Epub 2020 Jul 17.

Department of Nuclear Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

The present work aimed to assess reoxygenation and tumor inhibition during fractionated radiotherapy (FRT) in murine tumors using F-fluoromisonidazole (F-FMISO) and F-fluorothymidine (F-FLT) based micro positron emission tomography/computed tomography (PET/CT). A nude mouse xenograft model was established with the head and neck squamous carcinoma cell (FaDu), followed by administration of FRT. Imaging was carried out with both F-FMISO and F-FLT PET/CT, prior to FRT (Pre-FRT, 0 Gy), during FRT (Inter-FRT, 21 Gy), and after FRT (Post-FRT, 40 Gy). The maximum standardized uptake (SUVmax) and tumor-to-normal muscle ratio (TNR) were determined in regions of interest (ROIs) in F-FMISO and F-FLT PET/CT images. Then, hypoxic (HV) and proliferative tumor (PTV) volumes obtained by PET/CT were analyzed. Immunohistochemistry was performed to analyze the changes of hypoxia-inducible factor- (HIF)-1α, carbonic anhydrase 9 (CAIX), Ki67 and proliferating cell nuclear antigen (PCNA). Associations of the levels of these biomarkers with PET/CT parameters were analyzed. F-FMISO PET/CT demonstrated markedly elevated reduction rates of SUVmax (30.3 vs. 14.5%, = 0.012), TNR (27.9 vs. 18.3%, = 0.032) and HV (85.0 vs. 71.4%, = 0.047) from Pre-FRT to Inter-FRT compared with values from Inter-FRT to Post-FRT. Meanwhile, PTV reduction rate in F-FLT PET/CT from Pre-FRT to Inter-FRT was significantly decreased compared with that from Inter-FRT to Post-FRT (21.2 vs. 82.7%, = 0.012). Tumor HIF-1α, CAIX, Ki67, and PCNA amounts were continuously down-regulated during radiotherapy. TNR (FMISO) showed significant correlations with HIF-1α ( = 0.692, = 0.015) and CAIX ( = 0.801, = 0.006) amounts in xenografts, while associations of SUVmax (FMISO) with hypoxia markers were weak ( = 0.418, = 0.041 and = 0.389, = 0.037, respectively). SUVmax (FLT) was significantly correlated with Ki67 ( = 0.792, = 0.003) and PCNA ( = 0.837, = 0.004). Tumor reoxygenation occurs early during radiotherapy, while inhibition of cell proliferation by tumoricidal effects mainly takes place gradually with the course of radiotherapy. F-FMISO and F-FLT PET/CT are sensitive and non-invasive tools for the monitoring of tumor reoxygenation and proliferation during radiotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.01046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7379890PMC
July 2020

Current Trends in Research on Bone Regeneration: A Bibliometric Analysis.

Biomed Res Int 2020 27;2020:8787394. Epub 2020 May 27.

Department of Oral and Maxillofacial Surgery, Stomatological Hospital of Tianjin Medical University, Tianjin, China.

Background: Bone regeneration is a frequent research topic in clinical studies, but macroscopic studies on the clinical application of bone regeneration are rare. We conducted a bibliometric analysis, using international databases, to explore the clinical application and mechanism of bone regeneration, to highlight the relevant research hotspots and prospects. . Scientific reports on bone regeneration published during 2009-2019 were retrieved from PubMed. VOSviewer for cooccurrence keywords and authorship analysis. BICOMB software was used to retrieve high-frequency words and construct a text/coword matrix. The matrix was inputted into gCLUTO software, managed by biclustering analysis, in order to identify hotspots, which could achieve mountain and matrix visualizations. The matrix was also analyzed by using Ucinet 6 software for social network analysis. A strategic diagram was used for further analysis of the research hotspots of bone regeneration by "SCIMAT" software. We searched the Web of Science for relevant articles.

Results: Eighty-nine high-frequency major MeSH terms were obtained from 10237 articles and were divided into 5 clusters. We generated a network visualization map, an overlay visualization mountain map, and a social network diagram. Then, the MeSH terms were subdivided into 7 categories according to each diagram; current research hotspots were identified as scaffold, drug effect, osseointegration in dental implant, guided bone regeneration, factors impacting bone regeneration, treatment of bone and tissue loss, and bone regeneration in dental implants.

Conclusion: BICOMB, VOSviewer, and other bibliometric tools revealed that dental implants, scaffolds, and factors impacting bone regeneration are hot research topics, while scaffolds also hold promise from the perspective of bone tissue regeneration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/8787394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273498PMC
April 2021

Association between microRNA 21 expression in serum and lung cancer: A protocol of systematic review and meta-analysis.

Medicine (Baltimore) 2020 May;99(22):e20314

Fifth Ward of Internal Medicine Department, Affiliated Cancer Hospital of Harbin Medical University, Harbin, China.

Background: Previous studies have reported that microRNA 21 (mRNA 21) has involved in the procedure of lung cancer (LC). However, its conclusions are still unclear. Thus, this study will try to elaborate the association between mRNA 21 expression in serum and LC.

Methods: The electronic databases of Cochrane Library, PubMed, EMBASE, Allied and Complementary Medicine Database, WANGFANG database, and China National Knowledge Infrastructure will be retrieved from the inception to the present. All electronic databases will be searched without limitations of language and geographical location. Case-controlled studies reporting the association between mRNA 21 expression in serum and LC will be included. In addition, we will also identify other literature sources to avoid missing potential studies. All study selection, information collection, and study quality assessment will be performed by 2 independent authors. RevMan V.5.3 software and Stata V.12.0 software will be used for data synthesis and analysis.

Results: This study will summarize current evidence to investigate the association between mRNA 21 expression in serum and LC.

Conclusion: The findings of this study will present comprehensive evidence to determine whether mRNA 21 expression in serum is relevant with LC or not.

Systematic Review Registration: INPLASY202040055.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000020314DOI Listing
May 2020

[Construction and simulation mechanical analysis of dynamic knee joint finite element model based on CT image].

Zhongguo Gu Shang 2020 May;33(5):479-84

Department of Orthopaedics and Trauma, Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing 100102, China.

Objective: To construct a dynamic knee joint finite element model based on CT image data and verify the validity of the model. To provide a simulation model and basic data for biomechanical research of the knee joint by further finite element analysis.

Methods: The CT data of a healthy male knee joint was selected. With the help of Mimics 19.0 and Hypermesh 12.0 software, a high simulation finite element model of knee joint was established following steps, including geometric reconstruction, reverse engineering, meshing and material characterization. The dynamic knee flexion model was generated by determining the boundary conditions and torque loading, and the validity of themodel was confirmed. The biomechanical changes of the tibiofemoral and patellofemoral joints under different knee flexion angles were analyzed by applying the loads (500 N) to the finite element model during knee flexion.

Results: A finite element model of knee joint was established based on CT images and anatomical characteristics. The model included three-dimensional elements such as bone, ligament, cartilage, meniscus and patellar retinaculum. The different finite element models of knee flexion states were produced by applying different torques after establishing boundary conditions. According to equivalent conditions (knee flexion 30 degrees, quadriceps tendon under 200 N stretch), the peak stress value of patella was 2.209 MPa and the average Mises stress was 1.132 MPa; the peak stress value of femoral trochlear was 1.405 MPa and the average Mises stress was 0.936 MPa. The validity of the model was proved by the difference between the model and previous studies of 1% to 13.5%. Dynamic model loading showed that the Mises stressof tibiofemoral joint decreased with the increase of knee flexion angle, while the Mises stress of patellofemoral joint was positively correlated with knee flexion angle. The Mises stress of cartilage stress planes at different knee flexion angles was significantly different(<0.05).

Conclusion: The finite element model established in this study is more comprehensive and can effectively simulate the biomechanical characteristics of dynamic knee joint, which provides support for further simulation mechanics researches of the knee joint.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12200/j.issn.1003-0034.2020.05.018DOI Listing
May 2020

Association between microRNA 25 expression in serum and lung cancer: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2020 May;99(20):e20263

Department of Critical Medicine, First Affiliated Hospital of Jiamusi University, Jiamusi, China.

Background: This study aims to identify the association between microRNA 25 (mRNA 25) expression in serum and lung cancer (LC).

Methods: This planned study will cover all eligible case-controlled studies that report association between mRNA 25 expression in serum and LC. It will include published studies from inception to the present in Cochrane Library, PUBMED, EMBASE, Web of Science, Allied and Complementary Medicine Database, VIP database, and China National Knowledge Infrastructure regardless language and geographical location. We will also search other sources, such as conference abstracts and reference lists of related known studies and experts in the domain consulted to avoid missing potential studies. Two contributors will independently examine and select studies, collect all necessary data, and judge study quality for all included studies. We will perform statistical analysis using RevMan V.5.3 software and Stata V.12.0 software.

Results: This study will summarize current evidence to present first systematic review of research on the association between mRNA 25 expression in serum and LC.

Conclusion: This study will present comprehensive evidence to determine whether mRNA 25 expression in serum is associated with LC, and will provide helpful evidence for the future studies.

Systematic Review Registration: INPLASY202040056.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000020263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7254826PMC
May 2020

The pedigree analysis and prenatal diagnosis of Hong Kongαα Thalassemia and the sequence analysis of Hong Kongαα Allele.

Mol Genet Genomic Med 2020 07 18;8(7):e1285. Epub 2020 May 18.

Department of Genetics, Affiliated Hospital of Guilin Medical University, Guilin, People's Republic of China.

Background: Thalassemia is one of the most common monogenic hemolytic disorders in the world. Hong Kongαα (HKαα) thalassemia was initially found among the people of southern China. Because of the complexity of genetic changes in HKαα thalassemia, we lack a precise sequence analysis of the HKαα allele. Here we aim to detect the specific genotype and trace the law of inheritance of this rare genotype.

Methods: We recruited an unprecedented huge pedigree containing 11 individuals carrying the HKαα thalassemia gene and 4 nongenetic-related patients suffering from HKαα from south China. Regular hematological analysis and routine genetic screening were performed on the pedigree and two-round nested PCR (polymerase chain reaction) for HKαα thalassemia were performed on each individual. The first-generation gene sequencing was performed on six individuals, including four nongenetic-related patients.

Result: We found that five family members were positive for the HKαα allele. Patients Ⅱ-2, Ⅲ-1, and Ⅱ-3 with only HKαα/-- or HKαα/-α presented with α-thalassemia minor trait. Ⅰ-1, the carrier of both HKαα/-α and β /β , showed a typical β-thalassemia trait. Fetus with genotype HKαα/-α alone was not likely to suffer from any deleterious effects after birth. The whole sequence of HKαα allele revealed that HKαα alleles in the six patients shared a high similarity, implying that all HKαα alleles are likely from the same ancestor. Moreover, pedigree and sequencing analyses demonstrated that the HKαα allele contained ααα mutation, -α mutation, and a fragment from α-hemoglobin gene; thus, the composition and formation of HKαα allele was revealed. Finally, the high similarity and composition of HKαα alleles implies that once HKαα formed, ααα and -α mutations tended to be a fusion gene and quite impossible to be inherited separately.

Conclusion: The two-round nested PCR is an effective method to detect HKαα allele. Besides, our study for the first time revealed the sequence of the HKαα allele, the evidence of the same ancestor with HKαα thalassemia and enriched the composition as well as the formation mechanism of HKαα allele, and immediately opened up novel potential diagnosis and prenatal counseling for HKαα thalassemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mgg3.1285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336738PMC
July 2020

A Validated Model to Predict Postoperative Symptom Severity After Mandibular Third Molar Removal.

J Oral Maxillofac Surg 2020 06 6;78(6):893-901. Epub 2020 Mar 6.

Resident Physician, Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Tianjin Medical University, Tianjin, China.

Purpose: The individualized prediction of postoperative symptom severity is essential for selecting interventions after mandibular third molar (M3M) removal. The purpose of the present study was to develop and validate a nomogram for personal prediction of postoperative symptom severity.

Materials And Methods: A prospective cohort study was performed in the Stomatology Hospital of Tianjin Medical University. The sample was divided into training and testing data sets by time. The demographic, anatomic, radiographic, and operative variables were recorded. The self-reported postoperative symptom severity was recorded and defined as the primary outcome variable. Stepwise forward algorithms were applied to informative predictors based on Akaike's information criterion. Multivariable logistic regression analysis was used to develop the nomogram. An independent testing data set was used to validate the nomogram. Receiver operating characteristic curves and the Hosmer-Lemeshow test were used to assess model performance. P < .05 was considered to indicate statistical significance.

Results: The sample included 321 subjects who had undergone M3M removal. An independent validation data set included 103 consecutive patients. The median operation time was 15.0 minutes (interquartile range, 8.3 to 21.6 minutes) in the training data set (n = 218). Patients with serious postoperative symptoms accounted for 48.6 and 47.6% of the training and testing data sets, respectively. Gender, age, smoking status, operation time, Pell-Gregory ramus classification, and preoperative symptoms were identified as predictors and assembled into the nomogram. The area under curve demonstrated adequate discrimination in the validation data set (0.69; 95% confidence interval, 0.59 to 0.80). The nomogram was well calibrated, with a Hosmer-Lemeshow χ statistic of 6.33 (P = .78) in the testing data set. The confusion matrix was also summarized, and the accuracy was 63.3 and 65.1% in the training and testing data set, respectively.

Conclusions: The present study has proposed an effective nomogram with potential application in facilitating the individualized prediction of postoperative symptom severity after M3M removal.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.joms.2020.02.007DOI Listing
June 2020

CUBIC: an atlas of genetic architecture promises directed maize improvement.

Genome Biol 2020 01 24;21(1):20. Epub 2020 Jan 24.

National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan, 430070, China.

Background: Identifying genotype-phenotype links and causative genes from quantitative trait loci (QTL) is challenging for complex agronomically important traits. To accelerate maize gene discovery and breeding, we present the Complete-diallel design plus Unbalanced Breeding-like Inter-Cross (CUBIC) population, consisting of 1404 individuals created by extensively inter-crossing 24 widely used Chinese maize founders.

Results: Hundreds of QTL for 23 agronomic traits are uncovered with 14 million high-quality SNPs and a high-resolution identity-by-descent map, which account for an average of 75% of the heritability for each trait. We find epistasis contributes to phenotypic variance widely. Integrative cross-population analysis and cross-omics mapping allow effective and rapid discovery of underlying genes, validated here with a case study on leaf width.

Conclusions: Through the integration of experimental genetics and genomics, our study provides useful resources and gene mining strategies to explore complex quantitative traits.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13059-020-1930-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6979394PMC
January 2020

F-HX4/F-FMISO-based micro PET for imaging of tumor hypoxia and radiotherapy-associated changes in mice.

Biomed Pharmacother 2019 Nov 14;119:109454. Epub 2019 Sep 14.

Department of Nuclear Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, China. Electronic address:

Objective: The aim of this study was to evaluate the application of F-flortanidazole (F-HX4)/F-fluoromisonidazole (F-FMISO) - based micro positron emission tomography/computed tomography (PET/CT) for imaging of tumor hypoxia and radiotherapy-associated changes in mice.

Materials And Methods: Radiotracer-based cellular uptake was performed to explore the correlation between radiotracer uptake and hypoxia state in cells. Animal models were established using subcutaneous injection of the human breast cancer line (MDA-MB-231) in a nude mouse. The effect of radiotherapy on tumor xenograft was assessed by measuring the tumor volume and mouse survival time. Meanwhile, mice with xenograft were imaged with F-FMISO andF-HX4 PET/CT before and after radiotherapy. Tumor-to-normal muscle ratio (T/N) of F-FMISO andF-HX4 maximum uptake was calculated by selecting a region of interest. Changes in tumor biology were assessed with immunohistochemical staining; T/N (F-FMISO) and T/N (F-HX4) were analyzed in relation to tumor volume, survival time, and the expression of tumor biomarkers, including hypoxia-inducible factor (HIF)-1α, glucose transporter (Glut-1) and the proliferation antigen Ki67.

Results: Higher tracer uptake (both F-FMISO and F-HX4) was observed in hypoxic cells compared to oxygenated cell. The in vivo study suggested that both T/N (F-FMISO) and T/N (F-HX4) were positively correlated with tumor hypoxia volume (p = 0.014 and p = 0.009, respectively), but negatively associated with survival time (p = 0.012 and p = 0.007, respectively). HIF-1α, Glut-1 and Ki67 expression in tumors were downregulated after radiotherapy. T/N (F-HX4) was correlated with the expression of hypoxia marker HIF-1α in xenografts (r = 0.768, p = 0.025); while T/N (F-FMISO) was moderately correlated with the expressions of Ki67 (r = 0.412, p = 0.041). No significant correlation was detected between Glut-1 expression and T/N (F-FMISO) or T/N (F-HX4) (r = 0.511, p = 0.097 and r=0.562, p = 0.126, respectively).

Conclusions: Both F-HX4 and F-FMISO PET/CT can be used as biomarkers for tumor hypoxia and radiotherapy-associated changes. The clinical utilization of these two PET tracers needs to be further validated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biopha.2019.109454DOI Listing
November 2019
-->