Publications by authors named "Yong Hou"

243 Publications

Well-Defined Nanostructured Biointerfaces: Strengthened Cellular Interaction for Circulating Tumor Cells Isolation.

Adv Healthc Mater 2021 May 4:e2002202. Epub 2021 May 4.

Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustr. 3, Berlin, 14195, Germany.

The topographic features at the cell-material biointerface are critical for cellular sensing of the extracellular environment (ECM) and have gradually been recognized as key factors that regulate cell adhesion behavior. Herein, a well-defined nanostructured biointerface is fabricated via a new generation of mussel-inspired polymer coating to mimic the native ECM structures. Upon the bioinert background presence and biospecific ligands conjugation, the affinity of cancer cells to the resulting biofunctional surfaces, which integrate topographic features and biochemical cues, is greatly strengthened. Both the conjugated bioligand density, filopodia formation, and focal adhesion expression are significantly enhanced by the surficial nano-features with an optimized size-scale. Thus, this nanostructured biointerface exhibits high capture efficiency for circulating tumor cells (CTCs) with high sensitivity, high biospecificity, and high purity. Benefiting from the unique bioligands conjugation chemistry herein, the captured cancer cells can be responsively detached from the biointerfaces without damage for downstream analysis. The present biofunctional nanostructured interfaces offer a good solution to address current challenges to efficiently isolate rare CTCs from blood samples for earlier cancer diagnosis.
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http://dx.doi.org/10.1002/adhm.202002202DOI Listing
May 2021

Esophagus involvement in systemic sclerosis: ultrasound parameters and association with clinical manifestations.

Arthritis Res Ther 2021 Apr 21;23(1):122. Epub 2021 Apr 21.

Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 1 Shuaifuyuan Street, Dongcheng District, Beijing, 100730, China.

Background: The esophagus involvement in systemic sclerosis (SSc) is very common yet underestimated due to the lack of suitable screening tools. This study aims to explore the usefulness of ultrasound (US) in the assessment of esophagus involvement and to identify its relationship with clinical and CT manifestations.

Methods: We performed transabdominal esophageal US in 38 SSc patients and 38 controls. US parameters including the abdominal esophagus length, esophagus wall thickness, shear-wave elastography, gastro-esophageal (His) angle, and reflux were compared. Relationships between distinguishable US parameters and clinical/CT parameters, such as gastro-esophageal reflux disease questionnaire (GERDQ), modified Rodnan skin score (mRSS), interstitial lung disease (ILD) score, the largest esophagus diameter (Dmax), and esophagus dilation percentage (%Eop), were evaluated.

Results: Abdominal esophagus length was shorter in the SSc group than the control group (2.69 cm vs 3.06 cm, P = 0.018), whereas His angle and the angle change before and after drinking water were larger in the SSc group than the control group (121° vs 108°, P < 0.001; 7.97° vs 2.92°, P = 0.025). Reflux was more frequently seen in the SSc group than the control group (7/38 vs 0/38; P = 0.017). As for correlation with clinical and CT parameters, His angle was higher in patients with GERDQ ≥ 8 than GERDQ < 8 (116.5° vs 125.6°, P = 0.035). Patients with reflux showed higher ILD score than patients without (15.8 vs 9.6, P = 0.043). Furthermore, abdominal esophagus length was negatively correlated with %Eop and Dmax (r = - 0.573, P < 0.001; r = - 0.476, P = 0.003).

Conclusion: US parameters of the esophagus can distinguish SSc patients from controls, as well as have correlations with clinical and CT characteristics. Our pilot study first shows that US can be used as a noninvasive and convenient method to evaluate the esophagus involvement in SSc.
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http://dx.doi.org/10.1186/s13075-021-02505-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059267PMC
April 2021

Mitigation of Multiple Environmental Footprints for China's Pig Production Using Different Land Use Strategies.

Environ Sci Technol 2021 04 1;55(8):4440-4451. Epub 2021 Apr 1.

College of Resources and Environmental Sciences; National Academy of Agriculture Green Development; Key Laboratory of Plant-Soil Interactions, Ministry of Education, China Agricultural University, Beijing 100193, China.

Pig production contributes considerably to land use and greenhouse gas (GHG) and reactive nitrogen (Nr) emissions. Land use strategies were widely proposed, but the spillover effects on biological flow are rarely explored. Here, we simultaneously assessed the carbon (C), nitrogen (N), and cropland footprints of China's pig production at the provincial scale in 2017. The environmental impacts of land use strategies were further evaluated. Results show that one kg live-weight pig production generated an average of 1.9 kg CO-equiv and 59 g Nr emissions, occupying 3.5 m cropland, with large regional variations. A large reduction in GHG (58-64%) and Nr (12-14%) losses and occupied cropland (10-11%) could be achieved simultaneously if combined strategies of intensive crop production, improved feed-protein utilization efficiency, and feeding co-products were implemented. However, adopting a single strategy may have environmental side-effects. Reallocating cropland that pigs used for feed to plant food alternatives would enhance human-edible energy (3-20 times) and protein delivery (1-5 times) and reduce C and N footprints, except for rice and vegetables. Reallocating cropland to beef and milk production would decrease energy and protein supply. Therefore, a proper combination of land use strategies is essential to alleviate land use changes and nutrient emissions without sacrificing food supply.
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http://dx.doi.org/10.1021/acs.est.0c08359DOI Listing
April 2021

Comparison of relapsing polychondritis patients with and without central nervous system involvement: A retrospective study of 181 patients.

Int J Immunopathol Pharmacol 2021 Jan-Dec;35:20587384211000547

Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Graduate School of Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, China.

The relapsing polychondritis (RP) patients with central nervous system (CNS) involvement were rare. We aimed to determine the clinical characteristics of RP patients with CNS involvement. The clinical data of 181 RP patients, hospitalized at Peking Union Medical College Hospital between December 2005 and February 2019, were collected. The patients were categorized into two subgroups: 25 RP patients with CNS involvement, and 156 RP patients without CNS involvement. The involvement of the ear was more frequent in RP patients with CNS involvement, compared with those of RP patients without CNS involvement ( < 0.01). After controlling sex and the admission age, logistic regression analysis revealed hypertension (odds ratio = 4.308,  = 0.006) and involvement of eye (odds ratio = 5.158,  = 0.001) and heart (odds ratio = 3.216,  = 0.025) were correlated with RP patients with CNS involvement, respectively. In addition, pulmonary infection (odds ratio = 0.170,  = 0.020), tracheal involvement (odds ratio = 0.073,  < 0.01), and involvement of laryngeal (odds ratio = 0.034,  = 0.001), costochondral joint (odds ratio = 0.311,  = 0.013), sternoclavicular joint (odds ratio = 0.163,  = 0.017) and manubriosternal joint (odds ratio = 0.171,  = 0.021) were associated with RP patients without CNS involvement, respectively. In contrast to RP patients without CNS involvement, the incidence of ear involvement was higher in RP patients with CNS involvement. After controlling the potential confounding factor sex and the admission age, hypertension and involvement of eye and heart were related with RP patients with CNS involvement, respectively.
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http://dx.doi.org/10.1177/20587384211000547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995309PMC
March 2021

Increased co-expression of PSMA2 and GLP-1 receptor in cervical cancer models in type 2 diabetes attenuated by Exendin-4: A translational case-control study.

EBioMedicine 2021 Mar 6;65:103242. Epub 2021 Mar 6.

Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China. Electronic address:

Background: Type 2 diabetes (T2D) increases the risk of many types of cancer. Dysregulation of proteasome-related protein degradation leads to tumorigenesis, while Exendin-4, a glucagon-like peptide 1 receptor (GLP-1R) agonist, possesses anti-cancer effects.

Methods: We explored the co-expression of proteasome alpha 2 subunit (PSMA2) and GLP-1R in the Cancer Genome Atlas (TCGA) database and human cervical cancer specimens, supplemented by in vivo and in vitro studies using multiple cervical cancer cell lines.

Findings: PSMA2 expression was increased in 12 cancer types in TCGA database and cervical cancer specimens from patients with T2D (T2D vs non-T2D: 3.22 (95% confidence interval CI: 1.38, 5.05) vs 1.00 (0.66, 1.34) fold change, P = 0.01). psma2-shRNA decreased cell proliferation in vitro, and tumour volume and Ki67 expression in vivo. Exendin-4 decreased psma2 expression, tumour volume and Ki67 expression in vivo. There was no change in GLP-1R expression in 12 cancer types in TCGA database. However, GLP-1R expression (T2D vs non-T2D: 5.49 (3.0, 8.1) vs 1.00 (0.5, 1.5) fold change, P < 0.001) was increased and positively correlated with PSMA2 expression in T2D-related (r = 0.68)  but not in non-T2D-related cervical cancer specimens. This correlation was corroborated by in vitro experiments where silencing glp-1r decreased psma2 expression. Exendin-4 attenuated phospho-p65 and -IκB expression in the NF-κB pathway.

Interpretation: PSMA2 and GLP-1R expression in T2D-related cervical cancer specimens was increased and positively correlated, suggesting hyperglycaemia might promote cancer growth by increasing PSMA2 expression which could be attenuated by Exendin-4.

Funding: This project was supported by Postdoctoral Fellowship Scheme, Direct Grant, Diabetes Research and Education Fund from the Chinese University of Hong Kong (CUHK).
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http://dx.doi.org/10.1016/j.ebiom.2021.103242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938253PMC
March 2021

Multishock to Quasi-Isentropic Compression of Dense Gaseous Deuterium-Helium Mixtures up to 120 GPa: Probing the Sound Velocities Relevant to Planetary Interiors.

Phys Rev Lett 2021 Feb;126(7):075701

College of Physics, Sichuan University, Chengdu 610065, China.

Shock reverberation compression experiments on dense gaseous deuterium-helium mixtures are carried out to provide thermodynamic parameters relevant to the conditions in planetary interiors. The multishock pressures are determined up to 120 GPa and reshock temperatures to 7400 K. Furthermore, the unique compression path from shock-adiabatic to quasi-isentropic compressions enables a direct estimation of the high-pressure sound velocities in the unexplored range of 50-120 GPa. The equation of state and sound velocity provide particular dual perspectives to validate the theoretical models. Our experimental data are found to agree with several equation of state models widely used in astrophysics within the probed pressure range. The current data improve the experimental constraints on sound velocities in the Jovian insulating-to-metallic transition layer.
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http://dx.doi.org/10.1103/PhysRevLett.126.075701DOI Listing
February 2021

Integrated genetic analyses revealed novel human longevity loci and reduced risks of multiple diseases in a cohort study of 15,651 Chinese individuals.

Aging Cell 2021 03 3;20(3):e13323. Epub 2021 Mar 3.

Center for the Study of Aging and Human Development, Medical School of Duke University, Durham, USA.

There is growing interest in studying the genetic contributions to longevity, but limited relevant genes have been identified. In this study, we performed a genetic association study of longevity in a total of 15,651 Chinese individuals. Novel longevity loci, BMPER (rs17169634; p = 7.91 × 10 ) and TMEM43/XPC (rs1043943; p = 3.59 × 10 ), were identified in a case-control analysis of 11,045 individuals. BRAF (rs1267601; p = 8.33 × 10 ) and BMPER (rs17169634; p = 1.45 × 10 ) were significantly associated with life expectancy in 12,664 individuals who had survival status records. Additional sex-stratified analyses identified sex-specific longevity genes. Notably, sex-differential associations were identified in two linkage disequilibrium blocks in the TOMM40/APOE region, indicating potential differences during meiosis between males and females. Moreover, polygenic risk scores and Mendelian randomization analyses revealed that longevity was genetically causally correlated with reduced risks of multiple diseases, such as type 2 diabetes, cardiovascular diseases, and arthritis. Finally, we incorporated genetic markers, disease status, and lifestyles to classify longevity or not-longevity groups and predict life span. Our predictive models showed good performance (AUC = 0.86 for longevity classification and explained 19.8% variance of life span) and presented a greater predictive efficiency in females than in males. Taken together, our findings not only shed light on the genetic contributions to longevity but also elucidate correlations between diseases and longevity.
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http://dx.doi.org/10.1111/acel.13323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7963337PMC
March 2021

A genome-wide association study for gut metagenome in Chinese adults illuminates complex diseases.

Cell Discov 2021 Feb 9;7(1). Epub 2021 Feb 9.

BGI-Shenzhen, Shenzhen,, Guangdong 518083, China.

The gut microbiome has been established as a key environmental factor to health. Genetic influences on the gut microbiome have been reported, yet, doubts remain as to the significance of genetic associations. Here, we provide shotgun data for whole genome and whole metagenome from a Chinese cohort, identifying no <20% genetic contribution to the gut microbiota. Using common variants-, rare variants-, and copy number variations-based association analyses, we identified abundant signals associated with the gut microbiome especially in metabolic, neurological, and immunological functions. The controversial concept of enterotypes may have a genetic attribute, with the top two loci explaining 11% of the Prevotella-Bacteroides variances. Stratification according to gender led to the identification of differential associations in males and females. Our two-stage metagenome genome-wide association studies on a total of 1295 individuals unequivocally illustrates that neither microbiome nor GWAS studies could overlook one another in our quest for a better understanding of human health and diseases.
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http://dx.doi.org/10.1038/s41421-020-00239-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873036PMC
February 2021

Risk Factors in Patients with Diabetes Hospitalized for COVID-19: Findings from a Multicenter Retrospective Study.

J Diabetes Res 2021 15;2021:3170190. Epub 2021 Jan 15.

Beijing University of Chinese Medicine, Beijing, China.

Methods: In this multicenter retrospective study, patients with COVID-19 in China were included and classified into two groups according to whether they were complicated with diabetes or not. Demographic symptoms and laboratory data were extracted from medical records. Univariable and multivariable logistic regression methods were used to explore the risk factors.

Results: 538 COVID-19 patients were finally included in this study, of whom 492 were nondiabetes and 46 were diabetes. The median age was 47 years (IQR 35.0-56.0). And the elderly patients with diabetes were more likely to have dry cough, and the alanine aminotransferase, lactate dehydrogenase, Ca, and mean hemoglobin recovery rate were higher than the other groups. Furthermore, we also found the liver and kidney function of male patients was worse than that of female patients, while female cases should be paid more attention to the occurrence of bleeding and electrolyte disorders. Moreover, advance age, blood glucose, gender, prothrombin time, and total cholesterol could be considered as risk factors for COVID-19 patients with diabetes through the multivariable logistic regression model in our study.

Conclusion: The potential risk factors found in our study showed a major piece of the complex puzzle linking diabetes and COVID-19 infection. Meanwhile, focusing on gender and age factors in COVID-19 patients with or without diabetes, specific clinical characteristics, and risk factors should be paid more attention by clinicians to figure out a targeted intervention to improve clinical efficacy worldwide.
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http://dx.doi.org/10.1155/2021/3170190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847355PMC
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.
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http://dx.doi.org/10.3967/bes2020.123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817475PMC
December 2020

Multiregion single-cell sequencing reveals the transcriptional landscape of the immune microenvironment of colorectal cancer.

Clin Transl Med 2021 Jan;11(1):e253

Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China.

The tumor microenvironment is a complex ecosystem formed by distinct and interacting cell populations, and its composition is related to cancer prognosis and response to clinical treatment. In this study, we have taken the advantage of two single-cell RNA sequencing technologies (Smart-seq2 and DNBelab C4) to generate an atlas of 15,115 immune and nonimmune cells from primary tumors and hepatic metastases of 18 colorectal cancer (CRC) patients. We observed extensive changes in the proportions and functional states of T cells and B cells in tumor tissues, compared to those of paired non-tumor tissues. Importantly, we found that B cells from early CRC tumor were identified to be pre-B like expressing tumor suppressors, whereas B cells from advanced CRC tumors tended to be developed into plasma cells. We also identified the association of IgA IGLC2 plasma cells with poor CRC prognosis, and demonstrated a significant interaction between B-cell and myeloid-cell signaling, and found CCL8 cycling B cells/CCR5 T-cell interactions as a potential antitumoral mechanism in advanced CRC tumors. Our results provide deeper insights into the immune infiltration within CRC, and a new perspective for the future research in immunotherapies for CRC.
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http://dx.doi.org/10.1002/ctm2.253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775989PMC
January 2021

Genome diversity in Ukraine.

Gigascience 2021 Jan;10(1)

Department of Medicine, Uzhhorod National University, Uzhhorod 88000, Ukraine.

Background: The main goal of this collaborative effort is to provide genome-wide data for the previously underrepresented population in Eastern Europe, and to provide cross-validation of the data from genome sequences and genotypes of the same individuals acquired by different technologies. We collected 97 genome-grade DNA samples from consented individuals representing major regions of Ukraine that were consented for public data release. BGISEQ-500 sequence data and genotypes by an Illumina GWAS chip were cross-validated on multiple samples and additionally referenced to 1 sample that has been resequenced by Illumina NovaSeq6000 S4 at high coverage.

Results: The genome data have been searched for genomic variation represented in this population, and a number of variants have been reported: large structural variants, indels, copy number variations, single-nucletide polymorphisms, and microsatellites. To our knowledge, this study provides the largest to-date survey of genetic variation in Ukraine, creating a public reference resource aiming to provide data for medical research in a large understudied population.

Conclusions: Our results indicate that the genetic diversity of the Ukrainian population is uniquely shaped by evolutionary and demographic forces and cannot be ignored in future genetic and biomedical studies. These data will contribute a wealth of new information bringing forth a wealth of novel, endemic and medically related alleles.
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http://dx.doi.org/10.1093/gigascience/giaa159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804371PMC
January 2021

MicroRNA-320a: an important regulator in the fibrotic process in interstitial lung disease of systemic sclerosis.

Arthritis Res Ther 2021 01 11;23(1):21. Epub 2021 Jan 11.

Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.

Background: Systemic sclerosis (SSc) is an acquired autoimmune disorder characterized by excessive accumulation of collagen and progressive tissue fibrosis. Although interstitial lung disease (ILD) complicates the majority of SSc patients and is the leading cause of death, its pathogenesis remains largely unclear. In the current study, we aimed to evaluate the role of microRNAs in SSc-ILD.

Methods: miRNA expression patterns were assessed by miRNA array and real-time PCR from serum and PBMCs of SSc-ILD patients and healthy controls. Bleomycin-induced SSc-ILD mouse model was used to verify the miRNA expression in the lung tissue. The function of miRNAs in pulmonary fibroblasts was assessed using miRNA inhibitors, and mimics.

Results: miR-320a was significantly downregulated in both SSc-ILD patients and mouse models. The inhibition or overexpression of miR-320a in human pulmonary fibroblasts significantly affected the protein expression of type I collagen. Luciferase reporter assay, RT-PCR, and western blot analysis identified TGFBR2 and IGF1R as direct targets of miR-320a. Upon TGF-β stimulation, the expression of miR-320a and collagen genes were significantly upregulated.

Conclusion: miR-320a, together with its target genes, TGFBR2 and IGF1R, constituted a complex regulatory network, and played an important role in the fibrotic process of SSc-ILD. Investigation of more detailed mechanisms of miR-320a-mediated regulation of collagen expression may provide new therapeutic strategies for SSc-ILD.
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http://dx.doi.org/10.1186/s13075-020-02411-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802184PMC
January 2021

[Clinical Features of Relapsing Polychondritis Patients Presented with Arthropathy].

Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2020 Dec;42(6):717-722

Department of Rheumatology and Clinical Immunology,PUMC Hospital,CAMS and PUMC,Beijing 100730,China.

Objective To explore the clinical characteristics of relapsing polychondritis(RP)patients presented with arthropathy. Methods We retrospectively analyzed the clinical data of 201 RP patients who were hospitalized in our center between December 2005 and February 2019.After 16 patients with co-existing other autoimmune diseases and malignancies were ruled out,185 RP patients entered the final analysis,among whom 16 RP patients were presented with arthropathy and 169 without arthropathy.The demographic data,clinical manifestations,laboratory findings,and prognosis were compared between these two groups. Results Five of the 16 RP patients with arthropathy at presentation were misdiagnosed as rheumatoid arthritis.Compared with RP patients without arthropathy at presentation,RP patients with arthropathy at presentation had a longer disease course[(37.50±66.50)months (9.00±11.00)months,=-3.186, =0.001],longer time of diagnostic delay[(24.00±41.25)months (7.00±9.00)months,=-2.890,=0.004],and higher incidence of eye(62.50% 36.09%,=4.309,=0.038)and nervous system involvements(43.75% 15.38%,=6.205,=0.013). Conclusions RP patients with arthropathy at presentation are most likely to be misdiagnosed as rheumatoid arthritis.These patients are characterized by longer disease course and diagnostic delay and more frequrent eye and nervous system involvements.
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http://dx.doi.org/10.3881/j.issn.1000-503X.11914DOI Listing
December 2020

Single-cell landscape of the ecosystem in early-relapse hepatocellular carcinoma.

Cell 2021 Jan 23;184(2):404-421.e16. Epub 2020 Dec 23.

Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute Rockville, MD 20850, USA.

Hepatocellular carcinoma (HCC) has high relapse and low 5-year survival rates. Single-cell profiling in relapsed HCC may aid in the design of effective anticancer therapies, including immunotherapies. We profiled the transcriptomes of ∼17,000 cells from 18 primary or early-relapse HCC cases. Early-relapse tumors have reduced levels of regulatory T cells, increased dendritic cells (DCs), and increased infiltrated CD8 T cells, compared with primary tumors, in two independent cohorts. Remarkably, CD8 T cells in recurrent tumors overexpressed KLRB1 (CD161) and displayed an innate-like low cytotoxic state, with low clonal expansion, unlike the classical exhausted state observed in primary HCC. The enrichment of these cells was associated with a worse prognosis. Differential gene expression and interaction analyses revealed potential immune evasion mechanisms in recurrent tumor cells that dampen DC antigen presentation and recruit innate-like CD8 T cells. Our comprehensive picture of the HCC ecosystem provides deeper insights into immune evasion mechanisms associated with tumor relapse.
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http://dx.doi.org/10.1016/j.cell.2020.11.041DOI Listing
January 2021

Clinical features and risk factors for severe inpatients with COVID-19: A retrospective study in China.

PLoS One 2020 17;15(12):e0244125. Epub 2020 Dec 17.

President's Office, Beijing University of Chinese Medicine, Beijing, China.

Background: A worldwide outbreak of coronavirus disease (COVID-19), since 2019, has brought a disaster to people all over the world. Many researchers carried out clinical epidemiological studies on patients with COVID-19 previously, but risk factors for patients with different levels of severity are still unclear.

Methods: 562 patients with laboratory-confirmed COVID-19 from 12 hospitals in China were included in this retrospective study. Related clinical information, therapies, and imaging data were extracted from electronic medical records and compared between patients with severe and non-severe status. We explored the risk factors associated with different severity of COVID-19 patients by logistic regression methods.

Results: Based on the guideline we cited, 509 patients were classified as non-severe and 53 were severe. The age range of whom was 5-87 years, with a median age of 47 (IQR 35.0-57.0). And the elderly patients (older than 60 years old) in non-severe group were more likely to suffer from fever and asthma, accompanied by higher level of D-dimer, red blood cell distribution width and low-density lipoprotein. Furthermore, we found that the liver and kidney function of male patients was worse than that of female patients in both severe and non-severe groups with different age levels, while the severe females had faster ESR and lower inflammatory markers. Of major laboratory markers in non-severe cases, baseline albumin and the lymphocyte percentage were higher, while the white blood cell and the neutrophil count were lower. In addition, severe patients were more likely to be accompanied by an increase in cystatin C, mean hemoglobin level and a decrease in oxygen saturation. Besides that, advanced age and indicators such as count of white blood cell, glucose were proved to be the most common risk factors preventing COVID-19 patients from aggravating.

Conclusion: The potential risk factors found in our study have shown great significance to prevent COVID-19 patients from aggravating and turning to critical cases during treatment. Meanwhile, focusing on gender and age factors in groups with different severity of COVID-19, and paying more attention to specific clinical symptoms and characteristics, could improve efficacy of personalized intervention to treat COVID-19 effectively.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244125PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745975PMC
December 2020

Controllable ligand spacing stimulates cellular mechanotransduction and promotes stem cell osteogenic differentiation on soft hydrogels.

Biomaterials 2021 Jan 23;268:120543. Epub 2020 Nov 23.

Department of Cellular Biophysics, Max Planck Institute for Medical Research, Jahnstraße 29, 69120, Heidelberg, Germany; Department of Biophysical Chemistry, Heidelberg University, INF 253, 69120, Heidelberg, Germany.

Hydrogels with tunable mechanical properties have provided a tremendous opportunity to regulate stem cell differentiation. Hydrogels with osteoid (about 30-40 kPa) or higher stiffness are usually required to induce the osteogenic differentiation of mesenchymal stem cells (MSCs). It is yet difficult to achieve the same differentiation on very soft hydrogels, because of low environmental mechanical stimuli and restricted cellular mechanotransduction. Here, we modulate cellular spatial sensing of integrin-adhesive ligands via quasi-hexagonally arranged nanopatterns to promote cell mechanosensing on hydrogels having low stiffness (about 3 kPa). The increased interligand spacing has been shown to regulate actomyosin force loading to recruit extra integrins on soft hydrogels. It therefore activates mechanotransduction and promotes the osteogenic differentiation of MSCs on soft hydrogels to the level comparable with the one observed on osteoid stiffness. Our work opens up new possibilities for the design of biomaterials and tissue scaffolds for regenerative therapeutics.
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http://dx.doi.org/10.1016/j.biomaterials.2020.120543DOI Listing
January 2021

Self-Strengthening Adhesive Force Promotes Cell Mechanotransduction.

Adv Mater 2020 Dec 18;32(52):e2006986. Epub 2020 Nov 18.

Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustr. 3, Berlin, 14195, Germany.

The extracellular matrix (ECM) undergoes dynamic remodeling and progressive stiffening during tissue regeneration and disease progression. However, most of the artificial ECMs and in vitro disease models are mechanically static. Here, a self-strengthening polymer coating mimicking the dynamic nature of native ECM is designed to study the cellular response to dynamic biophysical cues and promote cell mechanical sensitive response. Spiropyran (SP) is utilized as dynamic anchor group to regulate the strength of cell adhesive peptide ligands. Benefiting from spontaneous thermal merocyanine-to-spiropyran (MC-SP) isomerization, the resulting self-responsive coating displays dynamic self-strengthening of interfacial interactions. Comparing with the static and all of the previous dynamic artificial ECMs, cells on this self-responsive surface remodel the weakly bonded MC-based coatings to activate α5β1 integrin and Rac signaling in the early adhesion stage. The subsequent MC-to-SP conversion strengthens the ligand-integrin interaction to further activate αvβ3 integrin and RhoA/ROCK signaling in the latter stage. This sequential process enhances cellular mechanotransduction as well as the osteogenic differentiation of mesenchymal stem cells (MSCs). It is worth emphasizing that the self-strengthening occurs spontaneously in the absence of any stimulus, making it especially useful for implanted scaffolds in regenerative medicine.
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http://dx.doi.org/10.1002/adma.202006986DOI Listing
December 2020

Tofacitinib as a possible treatment for skin thickening in diffuse cutaneous systemic sclerosis.

Rheumatology (Oxford) 2020 Nov 14. Epub 2020 Nov 14.

Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Science & Technology, Beijing, China.

Objectives: To analyse the effectiveness of tofacitinib for the treatment of refractory skin thickening in dcSSc.

Methods: Data from 10 patients with dcSSc treated with tofacitinib (5 mg twice daily) were analysed. A total of 12 dcSSc patients treated with intensive conventional immunosuppressants were selected as the historical comparator group. A clinically relevant response was defined as a decrease in the modified Rodnan skin score (mRSS) of >5 points and ≥25% from baseline. Clinical indicators were compared between the two groups to evaluate the effect of tofacitinib.

Results: The mRSS significantly improved the first month after tofacitinib treatment, with a mean change in the mRSS of -3.7 (95% CI -5.52, -1.88; P = 0.001) and greater than the comparators at 6 months [-10.0 (95% CI -14.74, -5.26) vs -4.1 (95% CI -7.49, -0.73), P = 0.026]. Tofacitinib-treated patients had a significantly shorter response time than the comparators (P = 0.015 by log-rank test), with overall response rates of 20% (2/10) vs 0% (0/12) and 60% (6/10) vs 16.7% (2/12) at 1 and 3 months, respectively.

Conclusion: Our results indicate that tofacitinib may be as effective as or even better than intensive conventional immunosuppressants, with a quicker and higher response rate in refractory dcSSc patients with progressive skin thickness.
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http://dx.doi.org/10.1093/rheumatology/keaa613DOI Listing
November 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.
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http://dx.doi.org/10.1016/j.phrs.2020.105290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833425PMC
November 2020

Risk and prognosis factors for systemic sclerosis with lung cancer: A single-centre case-control study in China.

Int J Clin Pract 2021 Apr 20;75(4):e13819. Epub 2020 Nov 20.

Department of Rheumatology and Clinical Immunology of Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.

Objective: To analyse clinical characteristics, risk and prognosis factors for systemic sclerosis (SSc) patients with lung cancer.

Methods: SSc patients with lung cancer admitted to Peking Union Medical College Hospital from February 1992 to December 2018 were included. Age and sex-matched controls were selected from a pool of SSc patients without lung cancer during the same period. Conditional logistic regression and Cox proportional-hazard regression were used to identify risk factors and prognosis factors. The Kaplan-Meier method was used to draw the survival curve and calculate median survival.

Results: Nineteen SSc patients with lung cancer and 76 controls were included. The mean age at lung cancer diagnosis was 54.4 ± 10.2 years. In all 19 cases the lung cancer had been diagnosed after SSc and the median interval between SSc onset and lung cancer onset was 10.5 years (range 2.0-36.2 years). Among SSc patients with lung cancer, the median follow-up time and median survival were 2.6 years and 1.4 years, respectively. In the sex and age-matched conditional logistic multivariable regression analysis, family history of malignancy (OR 4.930, 95%CI 1.926-12.619, P = .001), ILD (OR 7.701, 95%CI 1.009-58.767, P = .049) were independent risk factors for lung cancer among SSc patients, and considering sex and age of SSc onset, SSc patients with more advanced staging of lung cancer (HR 3.190, 95%CI 1.127-6.126, P = .06) had poorer prognosis.

Conclusion: Lung cancer is not uncommon in SSc patients, especially those with family histories of malignancy or ILD. Early detection of lung cancer is of vital importance for better prognosis.
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http://dx.doi.org/10.1111/ijcp.13819DOI Listing
April 2021

Embryonic liver developmental trajectory revealed by single-cell RNA sequencing in the Foxa2 mouse.

Commun Biol 2020 Nov 3;3(1):642. Epub 2020 Nov 3.

BGI-Shenzhen, 518033, Shenzhen, China.

The liver and gallbladder are among the most important internal organs derived from the endoderm, yet the development of the liver and gallbladder in the early embryonic stages is not fully understood. Using a transgenic Foxa2 reporter mouse line, we performed single-cell full-length mRNA sequencing on endodermal and hepatic cells isolated from ten embryonic stages, ranging from E7.5 to E15.5. We identified the embryonic liver developmental trajectory from gut endoderm to hepatoblasts and characterized the transcriptome of the hepatic lineage. More importantly, we identified liver primordium as the nascent hepatic progenitors with both gut and liver features and documented dynamic gene expression during the epithelial-hepatic transition (EHT) at the stage of liver specification during E9.5-11.5. We found six groups of genes switched on or off in the EHT process, including diverse transcripitional regulators that had not been previously known to be expressed during EHT. Moreover, we identified and revealed transcriptional profiling of gallbladder primordium at E9.5. The present data provides a high-resolution resource and critical insights for understanding the liver and gallbladder development.
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http://dx.doi.org/10.1038/s42003-020-01364-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642341PMC
November 2020

Genome-wide mutational signatures revealed distinct developmental paths for human B cell lymphomas.

J Exp Med 2021 Feb;218(2)

Department of Lymphoma, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.

Both somatic hypermutation (SHM) and class switch recombination (CSR) are initiated by activation-induced cytidine deaminase (AID). Dysregulation of these processes has been linked to B cell lymphomagenesis. Here we performed an in-depth analysis of diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL) genomes. We characterized seven genomic mutational signatures, including two B cell tumor-specific signatures, one of which is novel and associated with aberrant SHM. We further identified two major mutational signatures (K1 and K2) of clustered mutations (kataegis) resulting from the activities of AID or error-prone DNA polymerase η, respectively. K1 was associated with the immunoglobulin (Ig) switch region mutations/translocations and the ABC subtype of DLBCL, whereas K2 was related to the Ig variable region mutations and the GCB subtype of DLBCL and FL. Similar patterns were also observed in chronic lymphocytic leukemia subtypes. Thus, alterations associated with aberrant CSR and SHM activities can be linked to distinct developmental paths for different subtypes of B cell lymphomas.
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http://dx.doi.org/10.1084/jem.20200573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608067PMC
February 2021

New surgical paradigm for open neural tube defects.

Childs Nerv Syst 2021 Feb 21;37(2):529-538. Epub 2020 Aug 21.

Department of Paediatric Neurosurgery, Great Ormond Street Hospital for Children, NHS Trust, Great Ormond Street, London, WC1N3JH, UK.

Introduction: An open neural tube defect (ONTD) features an exposed, unclosed neural plate in the form of an expanded, flat, and frequently hefty neural placode. Traditional philosophy of ONTD repair aims at preserving function at any cost, which often means stuffing the entire thick and unwieldy but non-functional placode into a tight dural sac, increasing the likelihood of future tethering of the spinal cord. The same philosophy of attempting to save the whole perimetry of the placode also sometimes leads to inadvertent inclusion of parts of the squamous epithelial membrane surrounding the placode into the reconstructed product, only to form inclusion dermoid cyst causing further injury to the neural tissues. Lastly, defective closure of the caudal primary neural tube usually results in abolition of secondary and junctional neurulation, leaving a defective conus and sacral nerve roots, clinically presenting in most cases with neurogenic bladder and bowel dysfunction. Preserving this trapped but locally active sacral micturition center, isolated from suprasegmental inhibitory moderation, leads to a spastic, hyperactive, low compliance, and high-pressure bladder predisposing to upstream kidney damage, without benefits of normal bladder function.

Method And Material: We report the post-natal surgical treatment of 8 newborn infants with ONTD, in which we resected the non-functional portion of the neural placode identified as such by direct spinal cord/placode and nerve root stimulation, as well as by transcortical evoked motor responses to check for suprasegmental corticospinal connectivity. Any part of the placode without local function or upstream connections was resected, and the small caudal spinal cord stump closed with pia-to-pia microsutures. The patients were followed for pre- and post-operative neuro-urological status and with serial magnetic resonance imaging (MRI) at 3 weeks, 6 months, and 2 years post-repair. Follow-up period ranged from birth to 3 years (mean of 24 months).

Results: Of the 8 patients analyzed, 7 had a terminal and one a segmental ONTD. Pre-operative neurological level ranged from L4 to S2. Applying our new surgical paradigm, we found no neurological worsening post-operatively. All patients had a neurogenic bladder and bowel dysfunction but none had a high-pressure bladder on urodynamics studies. Early and late MRIs all showed a loose and capacious neural placode to dural sac relationship. None had an inclusion dermoid cyst.

Conclusion: We propose a new paradigm for the surgical repair of open neural tube defects with intraoperative neuromonitoring and introduce a safe and reliable technique of placode debulking.
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http://dx.doi.org/10.1007/s00381-020-04866-2DOI Listing
February 2021

Cathepsin-L is involved in degradation of fat body and programmed cell death in Bombyx mori.

Gene 2020 Nov 25;760:144998. Epub 2020 Jul 25.

State Key Laboratory of Silkworm Genome Biology, Southwest University, Beibei, Chongqing 400715, China; Biological Science Research Center, College of Biotechnology, Southwest University, Chongqing, Beibei, Chongqing 400715, China. Electronic address:

The life cycle of holometabolous insects involves different stages and cathepsin plays an important role in insect metamorphosis. In the present study, we investigated the function of Bombyx mori cathepsin-L (Bm-CatL) during metamorphosis and analyzed their role in programmed cell death (PCD) of the fat body. The results showed that knockdown of Bm-CatL by RNA interference led to abnormal pupation and a delay in fat body degradation during metamorphosis. Furthermore, PCD inhibition was observed in the fat body after downregulation of Bm-CatL. To confirm this finding, PCD was induced in Bombyx mori embryonic (BmE) cells by ultraviolet ray irradiation. We found that the PCD of BmE cells was weakened after knocking down Bm-CatL. Moreover, overexpression of Bm-CatL in cells promoted PCD. Overall, our results showed that Bm-CatL is involved in the degradation of internal tissues and promotes the PCD of cells involved in the pupation of silkworms. Thus, this study provides us with a better understanding for function of cathepsin-L during metamorphosis.
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http://dx.doi.org/10.1016/j.gene.2020.144998DOI Listing
November 2020

Clinical Characteristics of Peripheral Neuropathy in Eosinophilic Granulomatosis with Polyangiitis: A Retrospective Single-Center Study in China.

J Immunol Res 2020 4;2020:3530768. Epub 2020 Jul 4.

Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, The Ministry of Education Key Laboratory, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing 100730, China.

Objective: To investigate clinical features, independent associated factors, treatment, and outcome of patients with peripheral neuropathy (PN) in eosinophilic granulomatosis with polyangiitis (EGPA).

Methods: We retrospectively analyzed clinical data of 110 EGPA patients from 2007 to 2019 in Peking Union Medical College Hospital. The independent factors associated with PN in EGPA were analyzed with univariate and multivariate logistic regressions.

Results: In EGPA with PN, paresthesia and muscle weakness were observed in 82% and 33% of patients, respectively. Both the upper and lower limbs were involved in 51% of patients. 30% of EGPA patients had symmetrical multiple peripheral neuropathy, whereas only 16.4% presented with mononeuritis multiplex. Compared to patients without PN, patients with PN had a higher erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, Birmingham vasculitis activity score (BVAS), and positivity of myeloperoxidase-antineutrophil cytoplasmic antibodies (MPO-ANCA). Regarding manifestations, patients with PN tended to develop weight loss and arthritis or joint pain. Notably, ANCA positivity, arthritis or joint pain, and higher BVAS were found to be independent associated factors for PN in EGPA. Patients with PN more frequently need glucocorticoid pulses and intravenous infusion of cyclophosphamide. With the longest follow-up of 11.0 years, we found that age and cardiac involvement were risk factors for survival, and female was the protective factor.

Conclusion: PN in EGPA frequently displays with symmetrical multiple peripheral neuropathy in China. Positive ANCA, arthritis or joint pain, and higher BVAS are the independent associated factors of PN in EGPA. Glucocorticoids with immunosuppressants are vital therapeutic strategy.
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http://dx.doi.org/10.1155/2020/3530768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355369PMC
July 2020

Clinical features and long-term outcomes of Chinese patients with scleroderma renal crisis.

Int J Rheum Dis 2020 Aug 23;23(9):1194-1200. Epub 2020 Jul 23.

Department of Rheumatology, Peking Union Medical College Hospital, Clinical Immunology Center, Chinese Academy of Medical Sciences, Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, China.

Objective: To investigate the clinical features, treatments, and long-term outcomes of Chinese patients with scleroderma renal crisis (SRC).

Methods: We retrospectively reviewed the clinical and laboratory data of 538 patients with systemic sclerosis (SSc) at our center from January 2009 to December 2016, including 29 SRC and 509 SSc without SRC patients. The treatments and long-term outcomes of patients with SRC were also retrospectively analyzed.

Results: The prevalence of SRC was 5.4% in our cohort. Male gender (odds ratio [OR] =4.194 [95% CI 1.494-11.773]), glucocorticoid exposure (OR = 3.666 [1.484-9.056]), pericardial effusion (OR = 11.180 [4.515-27.681]), and myocardial involvement (OR = 7.958 [1.664-38.064]) were associated with an increased risk of development of SRC. Despite the wide use of angiotensin-converting enzyme inhibitors, the permanent dialysis rate of patients with SRC was 48.3%. Sixteen patients died during follow-up, and the estimated 1- and 5-year survival rates of patients with SRC were 62.1% and 47.3%, respectively. Withdrawal of dialysis (5 patients) and myocardial complications (3 patients) were the main causes of death in patients with SRC. Patients with serum creatinine level >500 µmol/L before treatment (log rank test 5.051, P = 0.025) and/or those who needed dialysis at the onset of SRC (log rank test 12.870, P < 0.001) showed poorer prognosis.

Conclusion: SRC is a rare but severe complication in patients with SSc. Male gender, glucocorticoid exposure, pericardial effusion, and myocardial involvement were risk factors in the development of SRC. Withdrawal of dialysis and myocardial complications were the main causes of death in Chinese patients with SRC.
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http://dx.doi.org/10.1111/1756-185X.13905DOI Listing
August 2020

Single-cell transcriptomics reveals regulators underlying immune cell diversity and immune subtypes associated with prognosis in nasopharyngeal carcinoma.

Cell Res 2020 11 20;30(11):1024-1042. Epub 2020 Jul 20.

Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, China.

Nasopharyngeal carcinoma (NPC) is an aggressive malignancy with extremely skewed ethnic and geographic distributions. Increasing evidence indicates that targeting the tumor microenvironment (TME) represents a promising therapeutic approach in NPC, highlighting an urgent need to deepen the understanding of the complex NPC TME. Here, we generated single-cell transcriptome profiles for 7581 malignant cells and 40,285 immune cells from fifteen primary NPC tumors and one normal sample. We revealed malignant signatures capturing intratumoral transcriptional heterogeneity and predicting aggressiveness of malignant cells. Diverse immune cell subtypes were identified, including novel subtypes such as CLEC9A dendritic cells (DCs). We further revealed transcriptional regulators underlying immune cell diversity, and cell-cell interaction analyses highlighted promising immunotherapeutic targets in NPC. Moreover, we established the immune subtype-specific signatures, and demonstrated that the signatures of macrophages, plasmacytoid dendritic cells (pDCs), CLEC9A DCs, natural killer (NK) cells, and plasma cells were significantly associated with improved survival outcomes in NPC. Taken together, our findings represent a unique resource providing in-depth insights into the cellular heterogeneity of NPC TME and highlight potential biomarkers for anticancer treatment and risk stratification, laying a new foundation for precision therapies in NPC.
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http://dx.doi.org/10.1038/s41422-020-0374-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784929PMC
November 2020

Chromatin accessibility and transcriptome landscapes of Monomorium pharaonis brain.

Sci Data 2020 07 8;7(1):217. Epub 2020 Jul 8.

BGI-Shenzhen, Shenzhen, 518083, China.

The emergence of social organization (eusociality) is a major event in insect evolution. Although previous studies have investigated the mechanisms underlying caste differentiation and social behavior of eusocial insects including ants and honeybees, the molecular circuits governing sociality in these insects remain obscure. In this study, we profiled the transcriptome and chromatin accessibility of brain tissues in three Monomorium pharaonis ant castes: queens (including mature and un-mated queens), males and workers. We provide a comprehensive dataset including 16 RNA-sequencing and 16 assay for transposase accessible chromatin (ATAC)-sequencing profiles. We also demonstrate strong reproducibility of the datasets and have identified specific genes and open chromatin regions in the genome that may be associated with the social function of these castes. Our data will be a valuable resource for further studies of insect behaviour, particularly the role of brain in the control of eusociality.
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http://dx.doi.org/10.1038/s41597-020-0556-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343836PMC
July 2020