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Showing papers by "Cheng Li published in 2022"


Journal ArticleDOI
TL;DR: The JNK pathway was identified as a major barrier to chemical reprogramming, the inhibition of which was indispensable for inducing cell plasticity and a regeneration-like program by suppressing pro-inflammatory pathways and provides a platform for the generation and application of human pluripotent stem cells in biomedicine.

83 citations



Journal ArticleDOI
TL;DR: This study generated islets from human chemically induced pluripotent stem cells (hCiPSC-islets) and shows that a one-dose intraportal infusion into diabetic non-human primates effectively restored endogenous insulin secretion and improved glycemic control.

37 citations


Journal ArticleDOI
TL;DR: In this paper , intermittent but not daily dosing of a PI3Kα/β/δ inhibitor, BAY1082439, on Pten-null prostate cancer models could overcome ICT resistance and unleash CD8+ T cell-dependent anti-tumor immunity in vivo.
Abstract: Combining immune checkpoint therapy (ICT) and targeted therapy holds great promises for broad and long-lasting anti-cancer therapies. However, combining ICT with anti-PI3K inhibitors have been challenging because the multifaceted effects of PI3K on both cancer cells and immune cells within the tumor microenvironment. Here we find that intermittent but not daily dosing of a PI3Kα/β/δ inhibitor, BAY1082439, on Pten-null prostate cancer models could overcome ICT resistance and unleash CD8+ T cell-dependent anti-tumor immunity in vivo. Mechanistically, BAY1082439 converts cancer cell-intrinsic immune-suppression to immune-stimulation by promoting IFNα/IFNγ pathway activation, β2-microglubin expression and CXCL10/CCL5 secretion. With its preferential regulatory T cell inhibition activity, BAY1082439 promotes clonal expansion of tumor-associated CD8+ T cells, most likely via tertiary lymphoid structures. Once primed, tumors remain T cell-inflamed, become responsive to anti-PD-1 therapy and have durable therapeutic effect. Our data suggest that intermittent PI3K inhibition can alleviate Pten-null cancer cell-intrinsic immunosuppressive activity and turn "cold" tumors into T cell-inflamed ones, paving the way for successful ICT.

30 citations


Journal ArticleDOI
TL;DR: In this paper , intermittent but not daily dosing of a PI3Kα/β/δ inhibitor, BAY1082439, on Pten-null prostate cancer models could overcome ICT resistance and unleash CD8+ T cell-dependent anti-tumor immunity in vivo.
Abstract: Combining immune checkpoint therapy (ICT) and targeted therapy holds great promises for broad and long-lasting anti-cancer therapies. However, combining ICT with anti-PI3K inhibitors have been challenging because the multifaceted effects of PI3K on both cancer cells and immune cells within the tumor microenvironment. Here we find that intermittent but not daily dosing of a PI3Kα/β/δ inhibitor, BAY1082439, on Pten-null prostate cancer models could overcome ICT resistance and unleash CD8+ T cell-dependent anti-tumor immunity in vivo. Mechanistically, BAY1082439 converts cancer cell-intrinsic immune-suppression to immune-stimulation by promoting IFNα/IFNγ pathway activation, β2-microglubin expression and CXCL10/CCL5 secretion. With its preferential regulatory T cell inhibition activity, BAY1082439 promotes clonal expansion of tumor-associated CD8+ T cells, most likely via tertiary lymphoid structures. Once primed, tumors remain T cell-inflamed, become responsive to anti-PD-1 therapy and have durable therapeutic effect. Our data suggest that intermittent PI3K inhibition can alleviate Pten-null cancer cell-intrinsic immunosuppressive activity and turn "cold" tumors into T cell-inflamed ones, paving the way for successful ICT.

29 citations


Journal ArticleDOI
TL;DR: In this article , a chemical cocktail enables the derivation of totipotent-like stem cells from 2-cell mouse embryos and extended pluripotent stem cells, and these TPS cells can be stably maintained long term.
Abstract: Abstract It is challenging to derive totipotent stem cells in vitro that functionally and molecularly resemble cells from totipotent embryos. Here, we report that a chemical cocktail enables the derivation of totipotent-like stem cells, designated as totipotent potential stem (TPS) cells, from 2-cell mouse embryos and extended pluripotent stem cells, and that these TPS cells can be stably maintained long term in vitro. TPS cells shared features with 2-cell mouse embryos in terms of totipotency markers, transcriptome, chromatin accessibility and DNA methylation patterns. In vivo chimera formation assays show that these cells have embryonic and extraembryonic developmental potentials at the single-cell level. Moreover, TPS cells can be induced into blastocyst-like structures resembling preimplantation mouse blastocysts. Mechanistically, inhibition of HDAC1/2 and DOT1L activity and activation of RARγ signaling are important for inducing and maintaining totipotent features of TPS cells. Our study opens up a new path toward fully capturing totipotent stem cells in vitro.

28 citations


Journal ArticleDOI
TL;DR: This work designed and verified an induced CTCF phase separation system in embryonic stem cells, which facilitated inter-A compartment interactions, improved self-renewal of ESCs and inhibited their differentiation toward neural progenitor cells.

13 citations


Journal ArticleDOI
TL;DR: This study provides a novel web server that could effectively predict the regulation of miRNAs expression by small molecules and predicted binding affinities of oncogenic mi RNAs and small molecules bore a close resemblance to the lowest binding energy profiles using molecular docking.
Abstract: Background: MicroRNAs (miRNAs) play key roles in a variety of pathological processes by interacting with their specific target mRNAs for translation repression and may function as oncogenes (oncomiRs) or tumor suppressors (TSmiRs). Therefore, a web server that could predict the regulation relations between miRNAs and small molecules is expected to achieve implications for identifying potential therapeutic targets for anti-tumor drug development. Methods: Upon obtaining positive/known small molecule-miRNA regulation pairs from SM2miR, we generated a multitude of high-quality negative/unknown pairs by leveraging similarities between the small molecule structures. Using the pool of the positive and negative pairs, we created the Dataset1 and Dataset2 datasets specific to up-regulation and down-regulation pairs, respectively. Manifold machine learning algorithms were then employed to construct models of predicting up-regulation and down-regulation pairs on the training portion of pairs in Dataset1 and Dataset2, respectively. Prediction abilities of the resulting models were further examined by discovering potential small molecules to regulate oncogenic miRNAs identified from miRNA sequencing data of endometrial carcinoma samples. Results: The random forest algorithm outperformed four machine-learning algorithms by achieving the highest AUC values of 0.911 for the up-regulation model and 0.896 for the down-regulation model on the testing datasets. Moreover, the down-regulation and up-regulation models yielded the accuracy values of 0.91 and 0.90 on independent validation pairs, respectively. In a case study, our model showed highly-reliable results by confirming all top 10 predicted regulation pairs as experimentally validated pairs. Finally, our predicted binding affinities of oncogenic miRNAs and small molecules bore a close resemblance to the lowest binding energy profiles using molecular docking. Predictions of the final model are freely accessible through the PSRR web server at https://rnadrug.shinyapps.io/PSRR/. Conclusion: Our study provides a novel web server that could effectively predict the regulation of miRNAs expression by small molecules.

7 citations


Journal ArticleDOI
TL;DR: In this article , the authors retrospectively reviewed all children with congenital clubfoot treated with the Ponseti method in Guilin Peoples' Hospital from June 2008 to June 2013.
Abstract: We retrospectively investigated the clinical materials to seek the factors that lead to relapse after using the Ponseti method.We retrospectively reviewed all children with congenital clubfoot treated with the Ponseti method in our hospital from June 2008 to June 2013. The data included the following factors: age, gender, initial Pinari score, number of casts, number of feet (unilateral or bilateral), age at the first casting, age of mother, tenotomy, walking age, and compliance with using bracing. All investigations were conducted in conformity with ethical standards. This study was approved by Guilin Peoples' Hospital Ethics Committee.In this study, there were 148 cases (164 ft) in total that underwent the Ponseti method, with the follow-up period at least 5 years. Of them, 64 children presented with left side, 58 with right side, and 26 with bilateral cases. This study included 75 males and 73 females; sex did not affect the outcomes. The mean age of the first casting was 2.50 ± 2.15 months. The average initial Pirani score was 4.98 ± 1.33, and the average number of casts was 5.71 ± 2.28 times. The mean age of mothers at birth was 25.81 ± 2.38 years old. The walking age of children was at a mean of 14.83 ± 1.18 months. Forty-nine cases could not tolerate using braces, namely the rate of noncompliance in this study was 33.1%. Tenotomy was performed on 113 ft (76.4%). The average follow-up period was 7.27 ± 1.29 years (from 5 to 10 years). The rate of relapse was 21.6% (32 cases) at the end of the follow-up. The rate of relapse in the noncompliance with using bracing group was significantly higher compared to the compliance group .The initial Pirani score, compliance with the foot abduction brace and the age at the first casting are three independent factors for relapse in clubfoot.

6 citations


Journal ArticleDOI
TL;DR: In this article , the authors performed multi-omics dissection of the HSC ontogeny trajectory across early arterial ECs, hemogenic endothelial cells (HECs), pre-HSCs and long-term HSCs.
Abstract: The gene activity underlying cell differentiation is regulated by a diverse set of transcription factors (TFs), histone modifications, chromatin structures and more. Although definitive hematopoietic stem cells (HSCs) are known to emerge via endothelial-to-hematopoietic transition (EHT), how the multi-layered epigenome is sequentially unfolded in a small portion of endothelial cells (ECs) transitioning into the hematopoietic fate remains elusive. With optimized low-input itChIP-seq and Hi-C assays, we performed multi-omics dissection of the HSC ontogeny trajectory across early arterial ECs (eAECs), hemogenic endothelial cells (HECs), pre-HSCs and long-term HSCs (LT-HSCs) in mouse embryos. Interestingly, HSC regulatory regions are already pre-configurated with active histone modifications as early as eAECs, preceding chromatin looping dynamics within topologically associating domains. Chromatin looping structures between enhancers and promoters only become gradually strengthened over time. Notably, RUNX1, a master TF for hematopoiesis, enriched at half of these loops is observed early from eAECs through pre-HSCs but its enrichment further increases in HSCs. RUNX1 and co-TFs together constitute a central, progressively intensified enhancer-promoter interactions. Thus, our study provides a framework to decipher how temporal epigenomic configurations fulfill cell lineage specification during development.

5 citations


Journal ArticleDOI
TL;DR: In this article , the authors performed multi-omics dissection of the HSC ontogeny trajectory across early arterial ECs, hemogenic endothelial cells (HECs), pre-HSCs and long-term HSCs.
Abstract: The gene activity underlying cell differentiation is regulated by a diverse set of transcription factors (TFs), histone modifications, chromatin structures and more. Although definitive hematopoietic stem cells (HSCs) are known to emerge via endothelial-to-hematopoietic transition (EHT), how the multi-layered epigenome is sequentially unfolded in a small portion of endothelial cells (ECs) transitioning into the hematopoietic fate remains elusive. With optimized low-input itChIP-seq and Hi-C assays, we performed multi-omics dissection of the HSC ontogeny trajectory across early arterial ECs (eAECs), hemogenic endothelial cells (HECs), pre-HSCs and long-term HSCs (LT-HSCs) in mouse embryos. Interestingly, HSC regulatory regions are already pre-configurated with active histone modifications as early as eAECs, preceding chromatin looping dynamics within topologically associating domains. Chromatin looping structures between enhancers and promoters only become gradually strengthened over time. Notably, RUNX1, a master TF for hematopoiesis, enriched at half of these loops is observed early from eAECs through pre-HSCs but its enrichment further increases in HSCs. RUNX1 and co-TFs together constitute a central, progressively intensified enhancer-promoter interactions. Thus, our study provides a framework to decipher how temporal epigenomic configurations fulfill cell lineage specification during development.

Journal ArticleDOI
TL;DR: The level of selenium in all subjects from the endemic areas was lower than normal, which reminds us to monitor the state of KBD constantly and adjust seenium salt supplementation in accordance with the changes in the KBD state.
Abstract: Selenium deficiency is one of the main risk factors for Kashin-Beck disease (KBD). This study aimed to detect the status of selenium and zinc in the urine of children from endemic areas of KBD over three consecutive years and to evaluate whether selenium and zinc levels in children in Shaanxi Province remain normal after stopping selenium supplementation. The samples of urine were collected in consecutive years (2017–2019) to detect selenium content by hydride generation atomic fluorescence spectrometry (HGAFS) and to detect zinc content by atomic absorption spectrophotometry (AAS). Generalized estimation equation (GEE) analysis was integrated to assess the comprehensive nutritional status and dietary structure of children. Data were processed in duplicate and analyzed by SPSS 18.0. This study included 30 X-ray-positive KBD cases and 123 healthy children aged 7–12 years. A total of 424 urine and 137 hair samples were collected over three consecutive years for selenium determination. The mean value of urinary selenium in all subjects was 6.86 μg/l (2017), 8.26 μg/l (2018), and 4.04 μg/l (2019), and the mean value of urinary zinc in all subjects was 0.36 mg/l (2017), 0.39 mg/l (2018), and 0.31 mg/l (2019) for the three consecutive years of 2017–2019. The mean values of urinary selenium were 6.56 and 6.94 μg/l (2017), 8.69 and 8.14 μg/l (2018), and 4.57 and 3.90 μg/l (2019) in the KBD-X and normal groups, respectively; and the mean value of urinary zinc were 0.38 and 0.35 mg/l (2017), 0.41 and 0.39 mg/l (2018), and 0.43 and 0.28 mg/l (2019) in the KBD-X and normal groups, respectively. The mean value of hair selenium in 137 subjects was 275.08 μg/kg and the mean values of hair selenium were 267.48 and 276.61 μg/kg in the KBD-X group and normal group, respectively. The level of selenium/zinc showed a trend of increasing first and then decreasing during the three consecutive years. The level of selenium in all subjects from the endemic areas was lower than normal, which reminds us to monitor the state of KBD constantly and adjust selenium salt supplementation in accordance with the changes in the KBD state.

Journal ArticleDOI
TL;DR: In this paper , the authors compared the gut microbiota structure between OA and KBD patients using 16S rDNA gene sequencing and found that the OA group was characterized by elevated Epsilonbacteraeota and Firmicutes levels, while the KBD group had higher Prevotella_9, Lactobacillus, Coprococcus_2, Senegalimassilia , and Holdemanella levels.
Abstract: Abstract Background Osteoarthritis (OA) and Kashin-Beck disease (KBD) both are two severe osteochondral disorders. In this study, we aimed to compare the gut microbiota structure between OA and KBD patients. Methods Fecal samples collected from OA and KBD patients were used to characterize the gut microbiota using 16S rDNA gene sequencing. To identify whether gut microbial changes at the species level are associated with the genes or functions of the gut bacteria between OA and KBD groups, metagenomic sequencing of fecal samples from OA and KBD subjects was performed. Results The OA group was characterized by elevated Epsilonbacteraeota and Firmicutes levels. A total of 52 genera were identified to be significantly differentially abundant between the two groups. The genera Raoultella , Citrobacter , Flavonifractor , g__Lachnospiraceae_UCG-004 , and Burkholderia-Caballeronia-Paraburkholderia were more abundant in the OA group. The KBD group was characterized by higher Prevotella_9 , Lactobacillus , Coprococcus_2 , Senegalimassilia , and Holdemanella . The metagenomic sequencing showed that the Subdoligranulum_sp._APC924/74 , Streptococcus_parasanguinis , and Streptococcus_salivarius were significantly increased in abundance in the OA group compared to those in the KBD group, and the species Prevotella_copri , Prevotella_sp._CAG:386 , and Prevotella_stercorea were significantly decreased in abundance in the OA group compared to those in the KBD group by using metagenomic sequencing. Conclusion Our study provides a comprehensive landscape of the gut microbiota between OA and KBD patients and provides clues for better understanding the mechanisms underlying the pathogenesis of OA and KBD.

Journal ArticleDOI
TL;DR: This study sampled the cubital venous blood of 258 subjects including 129 sex-matched KBD patients and 129 healthy controls for SNP detection and verified significantly upregulated PPARG, ADAM12, SMAD3, and TIMP2 in KBD compared with OA and normal controls.
Abstract: The mechanism of environmental factors in Kashin–Beck disease (KBD) remains unknown. We aimed to identify single nucleotide polymorphisms (SNPs) and protein alterations of selenium- and T-2 toxin–responsive genes to provide new evidence of chondrocytic damage in KBD. This study sampled the cubital venous blood of 258 subjects including 129 sex-matched KBD patients and 129 healthy controls for SNP detection. We applied an additive model, a dominant model, and a recessive model to identify significant SNPs. We then used the Comparative Toxicogenomics Database (CTD) to select selenium- and T-2 toxin–responsive genes with the candidate SNP loci. Finally, immunohistochemistry was applied to verify the protein expression of candidate genes in knee cartilage obtained from 15 subjects including 5 KBD, 5 osteoarthritis (OA), and 5 healthy controls. Forty-nine SNPs were genotyped in the current study. The C allele of rs6494629 was less frequent in KBD than in the controls (OR = 0.63, p = 0.011). Based on the CTD database, PPARG, ADAM12, IL6, SMAD3, and TIMP2 were identified to interact with selenium, sodium selenite, and T-2 toxin. KBD was found to be significantly associated with rs12629751 of PPARG (additive model: OR = 0.46, p = 0.012; dominant model: OR = 0.45, p = 0.049; recessive model: OR = 0.18, p = 0.018), rs1871054 of ADAM12 (dominant model: OR = 2.19, p = 0.022), rs1800796 of IL6 (dominant model: OR = 0.30, p = 0.003), rs6494629 of SMAD3 (additive model: OR = 0.65, p = 0.019; dominant model: OR = 0.52, p = 0.012), and rs4789936 of TIMP2 (recessive model: OR = 5.90, p = 0.024). Immunohistochemistry verified significantly upregulated PPARG, ADAM12, SMAD3, and TIMP2 in KBD compared with OA and normal controls (p < 0.05). Genetic polymorphisms of PPARG, ADAM12, SMAD3, and TIMP2 may contribute to the risk of KBD. These genes could promote the pathogenesis of KBD by disturbing ECM homeostasis.

Journal ArticleDOI
TL;DR: In this paper , the authors presented a study that used VR headsets to enhance affective expression and social reciprocity for children with ASD and explored how the approach could be effectively and sustainably delivered at schools.
Abstract: Social-emotional deficits in school-aged children diagnosed with autism spectrum disorder (ASD) greatly hinder these children from fully participating in various school activities in the inclusive education setting. Previous studies have demonstrated evidence regarding the effectiveness of using virtual reality (VR) for enhancing the children’s affective expression and social reciprocity. However, considering the technical and logistical complexity of the enabling hardware and software systems, how such approaches can be effectively and sustainably delivered in the school setting remains underexplored. This paper presents a study that utilised VR headsets to enhance affective expression and social reciprocity for children with ASD and explored how the approach could be effectively and sustainably delivered at schools. A total of eight VR learning scenarios were designed based on Kolb’s experiential learning framework. 176 children aged 6–12 with a clinical diagnosis of ASD participated in the study. The statistical analyses showed that the participants who received the intervention significantly improved in affective expression and social reciprocity, compared to those who were in the control group. Moreover, the approaches to enhance long-term sustainability have also been presented and discussed in this paper.

Journal ArticleDOI
TL;DR: The novel mixed cavity building model established by the “elastic stretch cavity builder” might provide the surgeon with additional longitudinal cervical operating space while improving the stability of the space and saving human effort.
Abstract: Objective To analyze the clinical characteristics of patients with large thyroid tumors underwent endoscopic thyroidectomy using the “elastic stretch cavity builder” system. Methods This retrospective case series study included thyroid tumor patients admitted to the Ningbo Medical Center Li Hui li Hospital between September 2017 and November 2021. The self-developed “elastic stretch cavity builder” was used to elastically lift the anterior cervical flap, combined with low-pressure (3 mmHg) high-flow CO2 inflation, and create a working cavity for endoscopic thyroidectomy. Results This study included 13 patients for analysis. The endoscopic thyroidectomy duration was 92-170 min (mean, 123 ± 24min). The maximum transverse plane diameter of the glands was 5.0-6.2 cm (mean, 5.3 ± 0.3 cm). The maximum sagittal plane diameter was 6.8-10.0 cm (mean, 7.6 ± 0.9 cm). After the “elastic stretch cavity builder” lifted the cervical flap, the height of the subcutaneous region was increased by 1.3 ± 0.2cm without affecting cervical activity. There was no residual scar in the anterior cervical skin puncture hole. All patients were satisfied with the cosmetic with the cosmetic satisfaction score was 3.4 ± 0.5. Conclusion The novel mixed cavity building model established by the “elastic stretch cavity builder” might provide the surgeon with additional longitudinal cervical operating space while improving the stability of the space and saving human effort.

Journal ArticleDOI
TL;DR: In this article , the authors correct the article DOI: 10.3389/fneur.2022.755492 and present a new version of the article, this article .
Abstract: [This corrects the article DOI: 10.3389/fneur.2022.755492.].

Posted ContentDOI
18 Dec 2022-bioRxiv
TL;DR: In this article , a single molecule super-resolution imaging was applied to reveal how SUN2 responds to actomyosin contractility, showing that SUN2 undergoes bidirectional translocation between ER and nuclear membrane.
Abstract: The trans-luminal LINC (Linker of Nucleoskeleton and Cytoskeleton) complex plays a central role in nuclear mechanotransduction by coupling the nucleus with cytoskeleton. High spatial density and active dynamics of LINC complex have hindered its precise characterization for the understanding of underlying mechanisms how the linkages sense and respond to mechanical stimuli. In this study, we focus on SUN2, a core component of LINC complex interconnecting the nuclear lamina and actin cytoskeleton and apply single molecule super-resolution imaging to reveal how SUN2 responds to actomyosin contractility. Using stochastic optical reconstruction microscopy (STORM), we quantitated the distribution pattern and density of SUN2 on the basal nuclear membrane. We found that SUN2 undergoes bidirectional translocation between ER and nuclear membrane in response to actomyosin contractility, suggesting that dynamic constrained force on SUN2 is required for its proper distribution. Furthermore, single molecule imaging unveils interesting dynamics of SUN2 molecules that are regulated by both actomyosin contractility and laminA/C network, whereas SUN2 oligomeric states are not affected by actomyosin contractility. Lastly, the mechanical response of SUN2 to actomyosin contractility was found to regulate expression of mechano-sensitive genes located in lamina-associated domains (LADs) and perinuclear heterochromatin. Taken together, our results reveal how SUN2 responds to mechanical cues at the single-molecule level, providing new insights into the mechanism of nuclear mechanotransduction.

Journal ArticleDOI
TL;DR: In this paper , the authors identify a pathway that is activated in response to Granulocyte Colony Stimulating Factor (G-CSF) treatment, which suppresses IFN-γ secretion in NK cells.

Journal ArticleDOI
TL;DR: In this paper , a randomised parallel longitudinal study investigating the use of virtual reality (VR) exposure to enhance intercultural sensitivity was conducted. And the results suggested that the intercultural sensitivities of the VR group was significantly enhanced in both within-subject comparisons and between-subject comparison.
Abstract: Prior studies suggest that emotional empathy is one of the components of intercultural sensitivity - the affective dimension under the concept of intercultural communication competence. Based on existing theories and findings, this paper reports a randomised parallel longitudinal study investigating the use of virtual reality (VR) exposure to enhance intercultural sensitivity. A total of 80 participants (36 females and 44 males) joined the study and were included in the data analysis. The participants were randomly assigned to the VR group, the video group, and the control group. Their intercultural sensitivity was measured three times: one week before the exposure ($T_{1}$), right after the exposure ($T_{2}$), and three weeks after the exposure ($T_{3}$). The results suggested that (1) the intercultural sensitivity of the VR group was significantly enhanced in both within-subject comparisons and between-subject comparisons, (2) there were no significant differences in intercultural sensitivity between the VR group and the video group at $T_{2}$, but the VR group retained the enhancement better at $T_{3}$, and (3) the sense of presence and emotional empathy well predicted the change in intercultural sensitivity of the VR group. The results, together with the participants' feedback and comments, provide new insights into the practice of using VR for intercultural sensitivity training and encourage future research on exploring the contributing factors of the results.

Journal ArticleDOI
TL;DR: Wang et al. as discussed by the authors performed a comprehensive genomic analysis using an FA patient (P1001) sample that transformed to MDS and subsequently AML, together with other three FA patient samples at the MDS stage.
Abstract: Abstract Background Fanconi anemia (FA) is a rare disease of bone marrow failure. FA patients are prone to develop myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). However, the molecular clonal evolution of the progression from FA to MDS/AML remains elusive. Methods Herein, we performed a comprehensive genomic analysis using an FA patient (P1001) sample that transformed to MDS and subsequently AML, together with other three FA patient samples at the MDS stage. Results Our finding showed the existence of polyclonal pattern in these cases at MDS stage. The clonal evolution analysis of FA case (P1001) showed the mutations of UBASH3A , SF3B1 , RUNX1 and ASXL1 gradually appeared at the later stage of MDS, while the IDH2 alteration become the dominant clone at the leukemia stage. Moreover, single-cell sequencing analyses further demonstrated a polyclonal pattern was present at either MDS or AML stages, whereas IDH2 mutated cell clones appeared only at the leukemia stage. Conclusions We thus propose a clonal evolution model from FA to MDS and AML for this patient. The results of our study on the clonal evolution and mutated genes of the progression of FA to AML are conducive to understanding the progression of the disease that still perplexes us.


Journal ArticleDOI
TL;DR: A review of the literature with particular attention to the clinical and radiological aspects of CDS is presented in this paper , where the authors focus on the radiology aspects of this syndrome.
Abstract: Defined as an association of acute cervical pain and calcifications in the peri-odontoid space, crowned dens syndrome (CDS) is a major imaging manifestation of “coronary”. CDS is a rare but under-recognized cause of severe neck pain in older adults. As such, it is often misdiagnosed. So, we review the literature with particular attention to the clinical and radiological aspects of this syndrome.

Journal ArticleDOI
TL;DR: Cervical chondromyxoid fibroma is a benign primary bone tumour that is rarely located in the vertebral bone and en bloc surgical resection of the tumour is the cornerstone of treatment.
Abstract: BACKGROUND Chondromyxoid fibroma (CMF) is an unusual benign tumour of cartilaginous tissues that may be confused with other malignant tumours. It is rarely seen in the cervical spine. CASE SUMMARY A 24-year-old young woman was admitted to the hospital because of neck and shoulder pain. Computed tomography, magnetic resonance imaging, X-ray and other imaging examinations of the cervical spine and laboratory-related indicators combined with intraoperative pathology revealed that the patient had cervical CMF. We performed total resection of the vertebral body and intervertebral disc, and internal fixation was performed to simultaneously maintain the stability of the entire spine. The clinical results from extensive resection were satisfactory. At the 2-year follow-up, the patient's symptoms had not recurred. CONCLUSION CMF is a benign primary bone tumour that is rarely located in the vertebral bone. Accurate initial diagnosis of these tumours is important for appropriate treatment. En bloc surgical resection of the tumour is the cornerstone of treatment.

Posted ContentDOI
Cheng Li, Wei Hu, Yang Lin, Xingming Lai, Xinyu Huang 
12 Jan 2022
TL;DR:
Abstract: Background To explore the correlation analysis of the vertebral compression degree and cancellous bone CT Hounsfield units (HUs) in elderly patients with osteoporotic thoracolumbar fractures. Methods Forty-five elderly patients (32 females and 13 males) with single acute vertebral fragility fractures were retrospectively reviewed, and thoracolumbar MRI was used to assess whether each patient's vertebral compression fracture was fresh and whether the fractured vertebral body was single.All patients were diagnosed with osteoporosis or osteopenia by DXA.The consistency of measurement between two spine surgeons were evaluated. If the cancellous bone CT HU values of the vertebral bodies could not be measured due to moderate or severe compression, the average cancellous bone CT HU values of the upper and lower vertebral bodies were used instead. Results There were 18 L1 vertebral fractures, 16 T12,6 L2,3 T11,and 2 T10 fractures. The patients’ average age was 70.89±9.59 years (53 to 94 years), and the average CT HU value was 92.01±34.11HU (36 to 167 HU). The average vertebral compression ratio was 0.54±0.16 (0.26 to 0.83).Measurements showed both good intrarater repeatability and good interrater reproducibility of the vertebral compression ratio (the intraclass correlation coefficient (ICC) was 0.982). The degree of vertebral compression in thoracolumbar osteoporotic fractures was highly positively correlated with the CT HU values of cancellous bone (P༜0.01). Conclusions This study provides the quantitative evidence that the degree of thoracolumbar osteoporotic compression fracture is associated with the CT HU units of cancellous bone in elderly patients. Further longitudinal studies with larger cohorts are needed to verify this relationship.