Publications by authors named "Yu Xia"

970 Publications

Xpert MTB/RIF Ultra enhances tuberculous pleurisy diagnosis for patients with unexplained exudative pleural effusion who underwent a pleural biopsy via thoracoscopy: a prospective cohort study.

Int J Infect Dis 2021 Apr 9. Epub 2021 Apr 9.

National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China. Electronic address:

Introduction: To evaluate the performance of Xpert MTB/RIF Ultra (Xpert-Ultra) in testing pleural tissue and fluid collected by medical thoracoscopy among patients with unexplained exudative pleural effusion.

Methods: Patients with an undiagnosed exudative pleural effusion were recruited prospectively and consecutively. Pleural tissue and fluid was collected by medical thoracoscopy and subjected to culture, Xpert MTB/RIF (Xpert) and Xpert-Ultra assays. Histopathological examination was also performed with the tissue and used as the major reference.

Results: Sixty one patients including 27 tuberculosis (TB) pleurisy, 15 malignancy and 19 other chronic infection cases were enrolled. The sensitivity, specificity, positive predict value and negative predict value of Xpert-Ultra for TB diagnosis were 85.19% (23/27), 97.06% (33/34), 95.83% (23/24) and 89.19% (33/37), respectively. Xpert-Ultra testing with the biopsy tissue alone had an equivalent diagnostic capacity to that of pathological examination for the diagnosis of confirmed TB cases. By combining pathological examination with Xpert-Ultra for biopsy, the percentage of confirmed TB cases increased greatly i.e. 92.59% (25/27). "Trace" positive outcome of Xpert-Ultra was highly supportive of TB diagnosis for both biopsy tissue and pleural fluid examinations.

Conclusion: With the specimens collected by medical thoracoscopy, Xpert-Ultra assay presented high value in identifying tuberculous among pleurisy patients who had difficulties in etiological diagnosis.
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http://dx.doi.org/10.1016/j.ijid.2021.04.011DOI Listing
April 2021

Identification of hub genes and compounds controlling ovarian cancer stem cell characteristics via stemness indices analysis.

Ann Transl Med 2021 Mar;9(5):379

Department of Obstetrics and Gynecology, Cancer Biology Research Center, Tongji Hospital, Tongji Medical College of HUST, Wuhan, China.

Background: Ovarian cancer (OC) is the most lethal gynecological malignancy. It has been reported that cancer stem cells (CSCs) play a crucial role in disseminated metastases in abdominal cavity and chemotherapy resistance of high-grade serous OC. However, the overall gene expression features of OC stem cells have not been clarified.

Methods: Expression datasets of 379 OC samples and 88 normal tissues were downloaded from The Cancer Genome Atlas (TCGA) and the Genotype Tissue Expression (GTEx) project. Differentially expressed genes (DEGs) were screened using the "limma" package in R software. Among the DEGs, modules and hub genes that were highly related to messenger RNA expression-based stemness index (mRNAsi) and epigenetically regulated mRNAsi indices were identified via weighted gene co-expression network analysis (WGCNA). These hub genes were considered to be associated with OC stem cells. The Gene Ontology (GO) project and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was used to identify the main biological processes that hub genes participated in. Finally, Connectivity Map (CMap) was used to predict compounds that disturb the hub genes.

Results: We identified 2,253 DEGs; of these, 31 had a significantly positive correlation to mRNAsi indices and were upregulated in OC, while 41 of them had a significantly negative correlation with mRNAsi indices and were downregulated in OC. Correlation analysis indicated that hub genes from the same module composed a dense interaction network. GO and KEGG enrichment analysis demonstrated that hub genes primarily play roles in cell division and proliferation. Moreover, the compounds that may disturb hub genes were identified. Of these, 11 compounds, including MS-275, DL-thiorphan, and GW-8510, which have never been studied in OC stem cells, were screened as underlying treatments targeting OC stem cells.

Conclusions: Altogether, 72 hub genes that were closely linked to OC stem cell characteristics were found to mainly participate in cell division and proliferation. Moreover, compounds that disturb these hub gens were identified and can be considered underlying targets for inhibiting OC stem cells.
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http://dx.doi.org/10.21037/atm-20-3621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033320PMC
March 2021

Quantifying evolutionary importance of protein sites: A Tale of two measures.

PLoS Genet 2021 Apr 7;17(4):e1009476. Epub 2021 Apr 7.

Department of Bioengineering, McGill University, Montreal, Quebec, Canada.

A key challenge in evolutionary biology is the accurate quantification of selective pressure on proteins and other biological macromolecules at single-site resolution. The evolutionary importance of a protein site under purifying selection is typically measured by the degree of conservation of the protein site itself. A possible alternative measure is the strength of the site-induced conservation gradient in the rest of the protein structure. However, the quantitative relationship between these two measures remains unknown. Here, we show that despite major differences, there is a strong linear relationship between the two measures such that more conserved protein sites also induce stronger conservation gradient in the rest of the protein. This linear relationship is universal as it holds for different types of proteins and functional sites in proteins. Our results show that the strong selective pressure acting on the functional site in general percolates through the rest of the protein via residue-residue contacts. Surprisingly however, catalytic sites in enzymes are the principal exception to this rule. Catalytic sites induce significantly stronger conservation gradients in the rest of the protein than expected from the degree of conservation of the site alone. The unique requirement for the active site to selectively stabilize the transition state of the catalyzed chemical reaction imposes additional selective constraints on the rest of the enzyme.
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http://dx.doi.org/10.1371/journal.pgen.1009476DOI Listing
April 2021

Deep-intronic and frameshift DSG1 variants associated with atypical severe dermatitis, multiple allergies and metabolic wasting (SAM) syndrome in a Chinese family.

Eur J Dermatol 2021 Apr 5. Epub 2021 Apr 5.

Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China, Institute of Dermatology, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Background: Severe dermatitis, multiple allergies and metabolic wasting (SAM) syndrome comprise a rare genodermatosis associated with biallelic (homozygous or compound heterozygous) mutations in the DSG1 (desmoglein-1) gene, or heterozygous mutations in the DSP (desmoplakin) gene. To date, while many patients with SAM syndrome have been described, the number of cases with SAM syndrome with deep-intronic variants, together its genetic aetiology, remain limited.

Objective: We report the case of a five-year-old Chinese boy with atypical SAM syndrome.

Materials & Methods: Relevant blood specimens from the family were collected. DNA isolation, RNA isolation and cDNA synthesis, and next-generation sequencing using a multi-gene panel were applied to verify the pathogenic gene. To test the functional consequences and pathogenic mechanism of the deep-intronic mutation in vitro, a mini gene strategy was constructed.

Results: A heterozygous DSG1 deletion (c.2437_2450delACCTATCCCTCGGG: p.Tyr814Trpfs*6) and a deep-intronic (c.1688-30A > T) variant were identified. The identified intronic variant was shown to create an alternative splice site, leading to nonsense-mediated mRNA decay of the aberrant transcript.

Conclusion: This is the first study to demonstrate a causal role for a deep-intronic DSG1 mutation in a patient with SAM syndrome. Our findings underline the need to analyse the intronic regions of DSG1 in patients with SAM syndrome. Improved diagnosis and a better understanding of prognosis will lead to clearer a picture of the concept of atypical SAM syndrome.
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http://dx.doi.org/10.1684/ejd.2021.4012DOI Listing
April 2021

Diagnostic Value of Sonographic Features in Distinguishing Malignant Partially Cystic Thyroid Nodules: A Systematic Review and Meta-Analysis.

Front Endocrinol (Lausanne) 2021 19;12:624409. Epub 2021 Mar 19.

Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China.

Ultrasonography (US) is one of the most important methods for the management of thyroid nodules, which can be classified as solid, partially cystic, or cystic by composition. The various Thyroid Imaging Reporting and Data System classifications pay more attention to solid nodules and have reported pertinent US features associated with malignancy. However, the likelihood of malignancy of partially cystic thyroid nodules (PCTNs) is 3.3-17.6%, and few studies have systematically discussed the value of US in differentiating such entities. Therefore, we deemed it necessary to perform a systematic evaluation of US features in recognizing malignant PCTNs. Our systematic review and meta-analysis aimed to assess the value of US features in predicting malignant PCTNs. We searched the PubMed/MEDLINE, Web of Science, and Cochrane Library databases to find studies that researched US features of PCTNs and that were published before June 2020. Review Manager 5.3 was used to summarize suspicious US features and calculate the sensitivity, specificity, and likelihood ratios. MetaDiSc 1.4 was used to estimate receiver operating characteristic curves and calculate areas under the curves (AUCs). Our review included eight studies with a total of 2,004 PCTNs. Seven features were considered to be associated with malignancy. High specificity (>0.9) was found in nodules with a taller-than-wide shape, those that were spiculated/microlobulated or with an ill-defined margin, those with microcalcification, and a non-smooth rim. Among US features, eccentric configuration, microcalcification, and marked or mild hypoechogenicity were more reliable in predicting malignancy (AUC: 0.9592, 0.8504, and 0.8092, respectively). After meta-analysis, we recommend combining PCTN US features including an eccentric internal solid portion, marked or mild hypoechogenicity, and presence of microcalcification to better identify malignant nodules. More studies are needed to explore and improve the diagnostic value of US in PCTNs.
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http://dx.doi.org/10.3389/fendo.2021.624409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018235PMC
March 2021

Deformation Resistance Performance of Carbon Fiber-Reinforced Plastic Machined by Controlling Drilling Area Temperature below the Glass Transition Temperature.

Materials (Basel) 2021 Mar 12;14(6). Epub 2021 Mar 12.

School of Mechanical Engineering, Xi'an Jiaotong University, Xi'an 710049, China.

Drilling of carbon fiber-reinforced plastics (CFRPs) is a challenging task in aviation and aerospace field. Damages, which can reduce the strength of the structure, often occur during secondary machining operations due to the applied cutting force and generated heat. The main objective of this study was to investigate the drilling performance and the deformation resistance of CFRPs subjected to cryogenic treatment based on glass transition temperature (Tg). Therefore, a cryogenic machining approach was adopted by fixing the workpiece inside a cryogenic box to drill CFRPs. The machining performance was briefly evaluated. Moreover, a through-hole drilling method was promoted to analyze the mechanism of different deformation mechanical properties. The results showed that the cryogenic machining approach improved the machining performance of CFRPs. Nevertheless, the residual intensity of cryo-treated specimen decreased (about 7.14%) due to the Tg-based viscoelasticity. These results demonstrate the great potential of this approach in advanced industrial applications and further pave the way for efficient secondary machining operation of CFRP components.
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http://dx.doi.org/10.3390/ma14061394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000319PMC
March 2021

The complete mitogenome of 'Dongfang No.3', an important cultivar in China.

Mitochondrial DNA B Resour 2021 Mar 19;6(3):1098-1100. Epub 2021 Mar 19.

Shandong Academy of Sciences, Qilu University of Technology, Jinan, PR China.

In this work, the complete mitogenome of cultivar 'Dongfang No.3' is reported. This mitogenome has a circular mapping organization with the length of 37,657 bp and contains 66 genes, including 35 protein-coding genes, three rRNAs, 25 tRNAs, and three open reading frames (s). The overall AT content is 64.73%, showing a higher AT content. The gene content and gene sequence are consistent with those reported varieties and cultivars of . Chinese main cultivars are analyzed by phylogenetic analysis. It indicates that 'Dongfang No.3' has a close relationship with , which strongly supports its genetic origin. The complete mitogenome analysis in this work would help in understanding the genetic background of Chinese cultivars.
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http://dx.doi.org/10.1080/23802359.2021.1899863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995842PMC
March 2021

Rainfall Influences Occurrence of Pharmaceutical and Personal Care Products in Landfill Leachates: Evidence from Seasonal Variations and Extreme Rainfall Episodes.

Environ Sci Technol 2021 Apr 1. Epub 2021 Apr 1.

Catalan Institute for Water Research (ICRA), C/Emili Grahit 101, Girona 17003, Spain.

Unused or expired pharmaceutical and personal care products (PPCPs) are usually discharged into municipal solid wastes, then travel to landfills, and eventually percolate into leachates. However, knowledge of their occurrence and temporal dynamics in leachates is limited, making landfill leachate an underappreciated emission source of PPCPs. Furthermore, the differences in PPCP variations in landfill leachates emphasize the necessity for identifying the influencing factors and elucidating the mechanisms for PPCP fluctuations. In this study, successive monthly monitoring of PPCPs in leachates throughout an entire year was performed to determine their seasonal variations and identify their influencing factors. Furthermore, five pairs of additional sampling campaigns were conducted before and after rainfall events during wet seasons to elucidate the influencing mechanisms. The results showed that there was a distinct seasonal variation in PPCPs in landfill leachates-elevated levels during the wet period (from April to September, with a mean concentration of 17.0 μg/L for total monitored PPCPs)-when compared to other months (mean concentration of 3.8 μg/L). Rainfall played a considerable role in mediating PPCP concentrations in leachates. The PPCP responses to five rainfall episodes further verified the influence of rainfall and demonstrated that the tendency to PPCP concentration increase was related to rainfall precipitation. Torrential rain events (i.e., 24 h cumulative precipitation of 50-99.9 mm) led to the most significant increases in PPCP concentrations in landfill leachates. In addition, the hydrophilicity of PPCPs contributed to the different fluctuations during the 1 year investigation and different responses to rainfall. To the best of our knowledge, this study provides the first direct evidence supporting the influence of rainfall on PPCPs in landfill leachates, which can help better understand the occurrence and behavior of emerging contaminants in this underappreciated emission source.
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http://dx.doi.org/10.1021/acs.est.0c07588DOI Listing
April 2021

Association of Hospital Safety Net Status With Outcomes and Resource Use for Extracorporeal Membrane Oxygenation in the United States.

J Intensive Care Med 2021 Mar 30:8850666211007062. Epub 2021 Mar 30.

Divisions of Cardiac Surgery, Cardiovascular Outcomes Research Laboratories, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.

Purpose: Safety net hospitals (SNH) have been associated with inferior surgical outcomes and increased resource use. Utilization and outcomes for extracorporeal membrane oxygenation (ECMO), a rescue modality for patients with respiratory or cardiac failure, may vary by safety net status. We hypothesized SNH to be associated with inferior outcomes and costs of ECMO in a national cohort.

Materials And Methods: The 2008-2017 National Inpatient Sample was queried for ECMO hospitalizations and safety net hospitals were identified. Multivariable regression was used to perform risk-adjusted comparisons of mortality, complications and resource utilization at safety net and non-safety net hospitals.

Results: Of 36,491 ECMO hospitalizations, 28.2% were at SNH. On adjusted comparison SNH was associated with increased odds of mortality (AOR: 1.23), tracheostomy use (AOR: 1.51), intracranial hemorrhage (AOR: 1.39), as well as infectious complications (AOR: 1.21, all < .05), with NSNH as reference. SNH was also associated with increased hospitalization duration (β=+4.5 days) and hospitalization costs (β=+$32,880, all < .01).

Conclusions: We have found SNH to be associated with inferior survival, increased complications, and higher costs compared to NSNH. These disparate outcomes warrant further studies examining systemic and hospital-level factors that may impact outcomes and resource use of ECMO at SNH.
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http://dx.doi.org/10.1177/08850666211007062DOI Listing
March 2021

Case Report: Whole-Exome Sequencing With MLPA Revealed Variants in Two Genes in a Patient With Combined Manifestations of Spinal Muscular Atrophy and Duchenne Muscular Dystrophy.

Front Genet 2021 10;12:605611. Epub 2021 Mar 10.

National Clinical Research Center for Child Health, Department of Neurology, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Spinal muscular atrophy (SMA) and Duchenne muscular dystrophy (DMD) are two common kinds of neuromuscular disorders sharing various similarities in clinical manifestations. SMA is an autosomal recessive genetic disorder that results from biallelic mutations of the survival motor neuron 1 gene (; OMIM 600354) on the 5q13 chromosome. DMD is an X-linked disorder caused by defects in the gene (OMIM 300377) on the X chromosome. Here, for the first time, we report a case from a Chinese family who present with clinical manifestations of both two diseases, including poor motor development and progressive muscle weakness. We identified a homozygous deletion in exons 7 and 8 of the gene and a deletion in exon 50 of the gene by whole-exome sequencing (WES) and multiplex ligation-dependent probe amplification (MLPA). This case expands our understanding of diagnosis for synchronous SMA and DMD and highlights the importance of various genetic testing methods, including WES, in differential diagnosis of neuromuscular diseases.
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http://dx.doi.org/10.3389/fgene.2021.605611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987946PMC
March 2021

miR‑519d‑3p/HIF‑2α axis increases the chemosensitivity of human cervical cancer cells to cisplatin via inactivation of PI3K/AKT signaling.

Mol Med Rep 2021 May 24;23(5). Epub 2021 Mar 24.

Department of Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi 341000, P.R. China.

Cisplatin (DDP)‑based chemotherapy is a standard treatment for cervical cancer, although chemotherapy resistance remains a major concern. Hypoxia‑inducible factor‑2 α (HIF‑2α) plays an important role in chemotherapy resistance. MicroRNAs (miRs) can inhibit gene expression by binding to the 3'‑untranslated region of the target gene. The authors' previous study showed that miR‑519d‑3p plays an important role in the regulation of HIF‑2α expression under hypoxic conditions in cervical cancer. However, the function and regulatory mechanisms of the miR‑519d‑3p/HIF‑2α axis in DDP‑resistance in cervical cancer are not fully understood. Therefore, the aim of the present study was to investigate whether the miR‑519d‑3p/HIF‑2α axis increased DDP resistance by regulating the PI3K/AKT signaling pathway. It was found that the expression of miR‑519d‑3p was lower in DDP‑resistant cervical cancer cells (CaSki/DDP and HeLa/DDP) compared with CaSki and HeLa cells under hypoxic conditions. Additionally, miR‑519d‑3p overexpression decreased the IC50 value in CaSki/DDP and HeLa/DDP cells, and inhibited HIF‑2α protein expression and the PI3K/AKT signaling pathway under hypoxic conditions. Furthermore, it was demonstrated that HIF‑2α overexpression reduced the effect of miR‑519d‑3p overexpression on HeLa/DDP and CaSki/DDP cells. Moreover, the present results suggested that HIF‑2α overexpression increased the IC50 value in CaSki/DDP and HeLa/DDP cells. It was also found that HIF‑2α overexpression reduced the effect of miR‑519d‑3p overexpression on the PI3K/AKT signaling pathway. Therefore, the present results indicated that the miR‑519d‑3p/HIF‑2α axis increased DDP resistance of cervical cancer cells by suppressing the PI3K/AKT signaling pathway under hypoxic conditions.
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http://dx.doi.org/10.3892/mmr.2021.11992DOI Listing
May 2021

Regiospecific 7-O-prenylation of anthocyanins by a fungal prenyltransferase.

Bioorg Chem 2021 Mar 2;110:104787. Epub 2021 Mar 2.

Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan 410013, People's Republic of China. Electronic address:

Anthocyanins are a type of well-known natural flavonoids for their various beneficial health effects. However, prenylated anthocyanins are not discovered in nature although prenylation is believed to generally enhance the biological accessibility of flavonoids. In this article, we demonstrate the first example for prenylation of anthocyanins. A chemo-enzymatic approach was achieved for the synthesis of a series of 7-O-prenylated anthocyanins, using the fungal prenyltransferase CdpC3PT from Neosartorya fischeri.
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http://dx.doi.org/10.1016/j.bioorg.2021.104787DOI Listing
March 2021

Acoustic Droplet Vitrification Method for High-Efficiency Preservation of Rare Cells.

ACS Appl Mater Interfaces 2021 Mar 11;13(11):12950-12959. Epub 2021 Mar 11.

Key Laboratory of Artificial Micro/Nano-Structures, Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan 430072, China.

Cryopreservation is a key step for current translational medicine including reproductive medicine, regenerative medicine, and cell therapy. However, it is challenging to preserve rare cells for practical applications due to the difficulty in handling low numbers of cells as well as the lack of highly efficient and biocompatible preservation protocols. Here, we developed an acoustic droplet vitrification method for high-efficiency handling and preservation of rare cells. By employing an acoustic droplet ejection device, we can encapsulate rare cells into water-in-air droplets with a volume from ∼pL to ∼nL and deposit these cell-containing droplets into a droplet array onto a substrate. By incorporating a cooling system into the droplet array substrate, we can vitrify hundreds to thousands of rare cells at an ultrafast speed (about ∼2 s) based on the high surface to volume ratio of the droplets. By optimizing this method with three different cell lines (a human lung cancer cell line, A549 cells, a human liver cell line, L02 cells, and a mouse embryonic fibroblast cell line, 3T3-L1 cells), we developed an effective protocol with excellent cell viability (e.g., >85% for days, >70% for months), proliferation, and adhesion. As a proof-of-concept application, we demonstrated that our method can rapidly handle and efficiently preserve rare cells, highlighting its broad applications in species diversity, basic research, and clinical medicine.
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http://dx.doi.org/10.1021/acsami.1c01452DOI Listing
March 2021

The acoustic droplet printing of functional tumor microenvironments.

Lab Chip 2021 Mar 8. Epub 2021 Mar 8.

Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan 430072, China.

The fabrication of functional tissue is important for tissue engineering, regenerative medicine, and biological research. However, current 3D bioprinting technologies mean it is hard to precisely arrange bioinks (composed of cells and materials) in a high-fidelity 3D structure and print cells of multiple types with sufficient concentrations and superior viabilities; this can severely constrain cell growth, interactions, and functions. Here, an acoustic droplet printing method is introduced to solve these problems in 3D bioprinting. Being nozzle-free, the acoustic printer stably enables high-concentration cells, or even cell spheroids, to be printed without clogging. Cell viability (>94%) using post acoustic printing is higher than those obtained with currently used inkjet-based (>85%) and extrusion-based (40-80%) bioprinting methods. Also, this method involves a small printer that can be flexibly integrated, allowing different kinds of bioinks to be printed. Moreover, the limited printability of low-concentration gelatin methacryloyl (5% (w/v) GelMA) materials is overcome by determining the positioning, fluidity (e.g., spreading), and 3D morphology of the GelMA droplets; therefore, high-fidelity 3D constructs can be fabricated. As a proof of concept, a tumor microenvironment consisting of one tumor spheroid surrounded by a high concentration of cancer-associated fibroblasts (CAFs) was constructed; this was able to establish a dynamic tumor invasion function modulated by reciprocal tumor cell-CAF interactions. The nozzle-free, contact-free, and low cell-damage merits of this method will advance bioprinting, allowing the creation of more functional native tissues, organoids, or disease models.
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http://dx.doi.org/10.1039/d1lc00003aDOI Listing
March 2021

ITM2A as a Tumor Suppressor and Its Correlation With PD-L1 in Breast Cancer.

Front Oncol 2020 12;10:581733. Epub 2021 Feb 12.

Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: High expression of integral membrane protein 2A (ITM2A) was reported to be associated with favorable prognosis in several solid tumors including breast cancer. This study aimed to investigate the role of ITM2A in breast cancer, especially in respect to tumor microenvironment.

Methods: ITM2A expression was evaluated based on qRT-PCR results on breast cancer specimens, as well as TCGA and GEO datasets. The influence of ITM2A expression on breast cancer cell proliferation and tumor growth were evaluated by CCK-8 assay, clonogenic assay, and murine xenograft models. Transwell assay was performed to observe the changes of invasion and migration capacity in breast cancer cells. To determine the biological functions of ITM2A, differentially expressed genes (DEGs) were screened based on RNA-sequencing data of MCF-7 cells overexpressed ITM2A. Then, functional annotation on DEGs was given by Gene Ontology and KEGG analysis. The stimulation on programmed cell death ligand 1 (PD-L1) expression when ITM2A overexpressed was determined by flow cytometry. Meanwhile, the correlation on expression levels between PD-L1 and ITM2A was tested qRT-PCR on 24 breast cancer tissues, as well as public database.

Results: We demonstrated that ITM2A was frequently downregulated in breast cancer. Patients with high expression levels of ITM2A had longer overall survival and relapse free survival. Overexpression of ITM2A inhibited proliferation and impaired cells capacity of invasion and migration and . The DEGs in breast cancer cells overexpressed ITM2A were found to be associated with immunity responses. Moreover, ITM2A was found to facilitate breast cancer cells to express PD-L1. The correlation between PD-L1 and ITM2A was verified with both qRT-PCR assay and public database. Additionally, it was found that breast cancer had higher ITM2A expression frequently had more tumor-infiltrating lymphocytes (TILs).

Conclusion: In summary, we found that high expression of ITM2A reduced the aggressivity of breast cancer cells and had a favorable effect on outcomes of patients with breast cancer. Moreover, ITM2A induced PD-L1 expression in breast cancer cells was accompanied with higher TILs numbers in tumor microenvironment.
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http://dx.doi.org/10.3389/fonc.2020.581733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928367PMC
February 2021

Comparative analysis of genomes reveals oomycete pathogenesis in crops.

Heliyon 2021 Feb 23;7(2):e06317. Epub 2021 Feb 23.

Animal & Plant Inspection and Quarantine Technology Center of Shenzhen Customs District P.R. China, Shenzhen 518045, China.

The oomycete genus includes devastating plant pathogens that are found in almost all ecosystems. We sequenced the genomes of two quarantined species- and . Comparing these species and related genera allowed reconstruction of the phylogenetic relationships within the genus and revealed genomic features associated with infection and pathogenicity. We found that several hundred genes are putatively inherited from red algae, but does not have vestigial plastids originating from phototrophs. The horizontally-transferred genes are abundant transposons that "transmit" exogenous gene to species thus bring about the gene recombination possibility. Several expansion events of gene families associated with cell wall biogenesis can be used as mutational targets to elucidate gene function in pathogenic interactions with host plants. This work enhanced the understanding of evolution and will also be helpful for the design of phytopathological control strategies.
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http://dx.doi.org/10.1016/j.heliyon.2021.e06317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907477PMC
February 2021

Acquired Hemophilia A in Wiskott-Aldrich Syndrome.

J Clin Immunol 2021 Mar 3. Epub 2021 Mar 3.

Department of Rheumatology and Immunology, Shenzhen Children's Hospital, China Medical University, 7019 Yitian Road, Shenzhen, 518038, China.

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http://dx.doi.org/10.1007/s10875-021-00978-9DOI Listing
March 2021

Three ultrasound phenotypes of non-invasive follicular thyroid neoplasm with papillary-like nuclear features proposed for imaging-pathology analysis: single center experience.

Gland Surg 2021 Jan;10(1):307-318

Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: The terminology "non-invasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP) was introduced to reduce overtreatment of thyroid carcinomas with indolent behavior. However, limited literature discussed the sonographic features of the entity in depth. The objective of this study is to summarize sonographic subtypes of NIFTP for precise diagnosis.

Methods: From January 2017 to June 2020, 13,531 consecutive patients underwent surgery for thyroid nodules were reviewed; 30 patients (0.22%) with 30 NIFTP were eligible for this retrospective observational study. We evaluated ultrasound features of all the lesions and distributed them into 3 major types of ultrasound appearance using pattern recognition. Systemic literature review concerning ultrasonography of NIFTP was also performed.

Results: At sonography, all the NIFTP lesions were classified into three types: 19 (63.3%) were categorized into type A-oval and solid nodule without other high-suspicion features, 7 (23.3%) into type B-partially cystic mass without high-suspicion features, 4 (13.3%) into type C-hypoechoic solid nodule with high-suspicion features including irregular margins, microcalcifications, taller-than-wide shape.

Conclusions: Three ultrasound patterns were proposed by us for ultrasound-cytopathology correlation analysis.
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http://dx.doi.org/10.21037/gs-20-612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882353PMC
January 2021

Multilevel clustering approach driven by continuous glucose monitoring data for further classification of type 2 diabetes.

BMJ Open Diabetes Res Care 2021 Feb;9(1)

Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affilated Sixth People's Hospital, Shanghai Clinical Center for Diabetes, Shanghai, China

Introduction: Mining knowledge from continuous glucose monitoring (CGM) data to classify highly heterogeneous patients with type 2 diabetes according to their characteristics remains unaddressed. A refined clustering method that retrieves hidden information from CGM data could provide a viable method to identify patients with different degrees of dysglycemia and clinical phenotypes.

Research Design And Methods: From Shanghai Jiao Tong University Affiliated Sixth People's Hospital, we selected 908 patients with type 2 diabetes (18-83 years) who wore blinded CGM sensors (iPro2, Medtronic, California, USA). Participants were clustered based on CGM data during a 24-hour period by our method. The first level extracted the knowledge-based and statistics-based features to describe CGM signals from multiple perspectives. The Fisher score and variables cluster analysis were applied to fuse features into low dimensions at the second level. The third level divided subjects into subgroups with different clinical phenotypes. The four subgroups of patients were determined by clinical phenotypes.

Results: Four subgroups of patients with type 2 diabetes with significantly different statistical features and clinical phenotypes were identified by our method. In particular, individuals in cluster 1 were characterized by the lowest glucose level factor and glucose fluctuation factor, and the highest negative glucose factor and C peptide index. By contrast, cluster 2 had the highest glucose level factor and the lowest C peptide index. Cluster 4 was characterized by the greatest degree of glucose fluctuation factor, was the most insulin-sensitive, and had the lowest insulin resistance. Cluster 3 ranked in the middle concerning the CGM-derived metrics and clinical phenotypes compared with those of the other three groups.

Conclusion: A novel multilevel clustering approach for knowledge mining from CGM data in type 2 diabetes is presented. The results demonstrate that subgroups are adequately distinguished with notable statistical and clinical differences.
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http://dx.doi.org/10.1136/bmjdrc-2020-001869DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908294PMC
February 2021

Intratumoral CXCL13CD8T cell infiltration determines poor clinical outcomes and immunoevasive contexture in patients with clear cell renal cell carcinoma.

J Immunother Cancer 2021 Feb;9(2)

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China

Background: Chemokine (C-X-C motif) ligand 13 (CXCL13) was known as a selective chemotaxis for B cells, a product of follicular helper CD4T cells (T) and a contributor to tertiary lymphoid structures (TLS). Although secretion and function of CXCL13 produced by T have been deeply explored, the immune function and prognostic significance of CXCL13 secreted by CD8T cells still remain unrevealed. This study aims to investigate the clinical merit of CXCL13CD8T cells in clear cell renal cell carcinoma (ccRCC).

Methods: We analyzed prognostic value and immune contexture that associated with CXCL13CD8T cells infiltration level in a total of 755 patients from Zhongshan Hospital cohort (n=223) and The Cancer Genome Atlas cohort (n=532). In vitro analyses were conducted on 42 samples of resected tumor tissue from Zhongshan Hospital in order to detect the immune status of CXCL13CD8T cells and total CD8T cells. Immunohistochemistry (IHC) and flow cytometry were applied to characterize immune cells and portray the tumor microenvironment (TME) in ccRCC.

Results: Intratumoral CXCL13CD8T cells abundance was associated with inferior overall survival and disease-free survival. CXCL13CD8T cells possessed higher level of immune checkpoints like programmed cell-death protein 1 (PD-1), T-cell immunoglobulin mucin 3 (Tim-3), T cell immunoreceptor with Ig and ITIM domains (TIGIT) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), higher Ki-67 expression and lower tumor necrosis factor α (TNF-α), interferon γ (IFN-γ) expression. Total CD8T cells in high-level CXCL13CD8T cells infiltration subgroup exhibited elevated exhausted markers (PD-1, Tim-3, TIGIT) and descended activated markers (TNF-α, IFN-γ) without quantity variance. Furthermore, the abundance of intratumoral CXCL13CD8T cell was correlated with immunoevasive TME accompanied by increased T helper 2 cells, tumor-associated macrophages, Foxp3 regulatory T cells, TLS and decreased natural killer cells, GZMB cells.

Conclusions: Intratumoral CXCL13CD8T cells infiltration indicated inferior clinical outcome in patients with ccRCC. CXCL13CD8T cells possessed increased exhausted markers, decreased effector molecules and better proliferation ability. CXCL13CD8T cells abundance impaired total CD8T cells' immune function. Intratumoral CXCL13CD8T cells abundance was associated with immunoevasive contexture. The abundance of CXCL13CD8T cells was an independent prognosticator and a potential immunotherapeutic target marker for ccRCC treatment.
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http://dx.doi.org/10.1136/jitc-2020-001823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887366PMC
February 2021

PRRX1 promotes lymph node metastasis of gastric cancer by regulating epithelial-mesenchymal transition.

Medicine (Baltimore) 2021 Feb;100(6):e24674

Department of Surgical Oncology, Gansu Provincial Hospital, Lanzhou.

Background: Gastric cancer has multiple metastasis pathways, of which lymph node metastasis plays a dominant role. However, the specific mechanism of lymph node metastasis is still not unclear.

Methods: The bioinformatics technology was utilized to mine gene chip data related to gastric cancer and Epithelial-Mesenchymal Transition (EMT) in a high-throughput gene expression database (Gene Expression Omnibus, GEO), we screened out all genes that have differential expression levels in gastric cancer tissues and in adjacent normal gastric mucosa tissues. The corresponding function package of R language software were performed for gene annotation and cluster analysis, then enrichment analysis of genes with differential expression and protein interaction network diagram for correlation analysis were performed, we finally screened out the paired related homeobox 1 gene (PRRX1) related to EMT. Next, we collected 65 metastatic lymph node samples and 93 gastric cancer tissue samples. The expression levels of PRRX1 and EMT-related protein E-cadherin (E-ca) and vimentin (Vim) in gastric cancer tissues and metastatic lymph node tissues were determined by immunohistochemistry (IHC) staining of streptavidin-peroxidase (SP). The expression differences of PRRX1, E-ca and Vim in gastric cancer tissues and metastatic lymph node tissues as well as the correlation were analyzed by the experimental data, and the clinical significance was analyzed in combination with the clinicopathological data.

Results: The PRRX1 expression levels in gastric cancer tissues are significantly higher than that in adjacent normal gastric mucosa tissues. The positive expression rates of PRRX1, Vim and E-ca in gastric cancer and in metastatic lymph node tissues were significantly different. Comparing with that in gastric cancer, expression of PRRX1 and Vim was significantly down-regulated, and E-ca expression was significantly up-regulated in metastatic lymph nodes.

Conclusion: PRRX1 may promote lymph node metastasis of gastric cancer by regulating EMT, and then affect the prognosis of patients. PRRX1 may be used as a new biological indicator to predict or prevent lymph node metastasis in gastric cancer.
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http://dx.doi.org/10.1097/MD.0000000000024674DOI Listing
February 2021

Prevalence and molecular characterizations of seven additional drug resistance among multidrug-resistant tuberculosis in China: A subsequent study of a national survey.

J Infect 2021 Mar 5;82(3):371-377. Epub 2021 Feb 5.

National Tuberculosis Clinical Laboratory, Beijing Key laboratory for Drug-resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beiguan St #9, Beijing 101149, China. Electronic address:

The drug resistance prevalence data facilitates selection of the initial drug for treating multidrug-resistant tuberculosis (MDR-TB). The aim of this study was to investigate the prevalence and molecular characterization of seven additional types of drug resistances among MDR-TB isolates collected from the first/only nationwide drug resistance surveillance in China. A total of 391 out of the 401 MDR-TB strains were successfully recovered by Löwenstein-Jensen medium. Drug susceptibility testing was performed against moxifloxacin (Mfx), bedaquiline (Bdq), linezolid (Lzd), clofazimine (Cfz), cycloserine (Cs), delamanid (Dlm) and pyrazinamide (PZA). The strains were subjected to whole-genome sequencing for the analysis corresponding drug resistant genes and their profiles. 269 (68.80%) were simple MDR-TB, 28 (7.16%) were extensively drug-resistant tuberculosis (XDR-TB) and 94 (24.04%) were pre-XDR-TB. Dlm, Lzd, Cfz and Bdq presented the lowest drug resistant rates i.e. 3.32% (13/391), 3.84% (15/391),6.65% (26/391) and 7.16% (28/391), respectively. Mfx (17.39%, 68/391) and CS (13.55%, 53/391) also demonstrated strong potencies against the MDR strains, whereas PZA (38.36%, 150/391) presented much higher resistant rate. 54.41% (37/68) Mfx-resistant strains carried mutations located within gyrA or gyrB. 70.15% (94/134) PZA-resistant strains had pncA mutations. Two of the 26 Cfz-resistant isolates had mutation in Rv0678 were also resistant to Bdq. Dlm, Lzd, Cfz and Bdq exhibited excellent activity against MDR-TB, including XDR-TB. These data highlighted the necessity of a timely, feasible and reliable DST, while genotypic DST for Mfx and PZA is promising at this moment.
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http://dx.doi.org/10.1016/j.jinf.2021.02.004DOI Listing
March 2021

Effect of Gentamicin Ointment in Patients with Nagashima-type Palmoplantar Keratosis: A Double-blind Vehicle-controlled Study.

Acta Derm Venereol 2021 Feb 11;101(2):adv00392. Epub 2021 Feb 11.

Departments of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 200092 Shanghai, China.

Gentamicin ointment has potential in the treatment of Nagashima-type palmoplantar keratosis. However, there is a lack of reliable study data. The aim of this study was to perform a prospective, randomized, double-blinded, contralateral, vehicle-controlled clinical trial. A total of 20 subjects diagnosed with Nagashima-type palmoplantar keratosis by genetic test, who carried nonsense mutations, enrolled in the 30-day study. Gentamicin ointment was applied to the hand and foot on one side of the body, and vehicle ointment was applied to the hand and foot on the other side. The choice of hand and foot in each subject was randomly allocated. The severity of the patient's skin lesions and quality of life were assessed by a blinded evaluator, using the Dermatology Life Quality Index, visual analogue scale scores and digital photography. Gentamicin ointment treatment resulted in a significant improvement in symptoms of hyperkeratosis and foul smell compared with vehicle. No difference was found in the effect on erythema between gentamicin and vehicle. In conclusion, gentamicin ointment demonstrated positive responses and good tolerance in treating Nagashima-type palmoplantar keratosis caused by nonsense mutations.
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http://dx.doi.org/10.2340/00015555-3760DOI Listing
February 2021

Severe skeletal bimaxillary protrusion treated with micro-implants and a self-made four-curvature torquing auxiliary: A case report.

World J Clin Cases 2021 Jan;9(3):722-735

Department of Stomatology, Daping Hospital, Third Military Medical University (Army Military Medical University), Chongqing 400042, China.

Background: Bimaxillary protrusion is a clinically common dentofacial deformity, particularly among Chinese patients. This kind of malformation can severely affect facial esthetics and, even in mild cases, is difficult to correct without surgery. Unfortunately, many patients abandon treatment because of fear of surgery. Here, we describe a case of severe skeletal bimaxillary protrusion treated with nonsurgical orthodontic treatments, highlighting an alternative treatment option.

Case Summary: A 31-year-old woman wished to address a severe protrusion profile (approximately 8 mm overbite) and gummy smile. Cephalometric analysis and superimposition showed a severe skeletal class II pattern with a mandibular retrusion, and proclined and protrusive mandibular incisors. Panoramic radiograph showed a missing mandibular right third molar. A diagnosis of severe bimaxillary dentoalveolar protrusion was made. Taking into account the patient's fear of orthognathic surgery, she accepted the proposed alternative treatment using micro-implants and a self-made four-curvature torquing auxiliary. The treatment allowed for maximal anterior tooth retraction, proper relocation of incisors, and alleviation of the skeletal class II pattern. Esthetically, the patient's lip protrusion was significantly decreased as was the overjet (from 10.5 mm to 1.8 mm), and the results remained stable throughout the 2-year follow-up.

Conclusion: Nonsurgical treatment using micro-implants and a four-curvature torquing auxiliary may benefit severe cases of skeletal bimaxillary protrusion in adults.
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http://dx.doi.org/10.12998/wjcc.v9.i3.722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829714PMC
January 2021

Hepatoprotective effects of oridonin against bisphenol A induced liver injury in rats via inhibiting the activity of xanthione oxidase.

Sci Total Environ 2021 May 21;770:145301. Epub 2021 Jan 21.

Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Co-innovation Center of Henan Province for New drug R & D and preclinical Safety, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, PR China. Electronic address:

Bisphenol A (BPA) is widely used to manufacture packaging materials for various daily necessities and causes harmful effects in organs, especially liver injury, by generating oxidative stress. Oridonin, an active diterpenoid isolated from Rabdosia rubescens (Hemsl.) Hara, has been reported to possess a wide range of pharmacological activities including anti-inflammatory, antioxidative and antiapoptotic effects. However, the role of oridonin in BPA--induced liver injury and its potential protective mechanism have not been well characterized. In this research, we explored the metabolic alterations in the liver tissue of rats after exposure to BPA with or without pretreatment with oridonin for 14 days by metabolomics analysis based on UPLC-MS/MS. Rats were randomly divided into groups as follows: Control, Vehicle, Oridonin (10 mg/kg), Bisphenol A (500 mg/kg), bisphenol A + Oridonin (500 + 10 mg/kg), Bisphenol A + Diammonium glycyrrhizinate (500 + 40 mg/kg). The biochemical results showed that oridonin significantly reduced the levels of AST and ALT (P < 0.05), ameliorated the abnormal histopathological changes and reduced hepatic apoptosis compared with the BPA group. Furthermore, metabolomics results revealed that purine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis and phenylalanine metabolism were reprogrammed, based on 28 identified significant differential metabolites among the Vehicle, BPA and BPA + oridonin groups. In-depth studies demonstrated that pretreatment with oridonin may play a protective role by restoring BPA-induced changes in oxidative stress and the activity of oxidase (XOD) (P < 0.05). Additionally, oridonin could inhibit the activity of XOD by binding to it, therefore decreasing the reactive oxygen species (ROS) level, upregulating the content of hypoxanthine and xanthine, and reducing the level of uric acid in the liver (P < 0.05). This research presents the potential protective mechanisms of oridonin on BPA-induced liver injury at the metabolic level, which might be used to identify new protective agents that prevent BPA-induced liver injury.
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http://dx.doi.org/10.1016/j.scitotenv.2021.145301DOI Listing
May 2021

miRNA-Based Feature Classifier Is Associated with Tumor Mutational Burden in Head and Neck Squamous Cell Carcinoma.

Biomed Res Int 2020 9;2020:1686480. Epub 2020 Dec 9.

Department of Oral and Maxillofacial Surgery, Guizhou Provincial People's Hospital, Guizhou, China.

Tumor mutation burden (TMB) is considered to be an independent genetic biomarker that can predict the tumor patient's response to immune checkpoint inhibitors (ICIs). Meanwhile, microRNA (miRNA) plays a key role in regulating the anticancer immune response. However, the correlation between miRNA expression patterns and TMB is not elucidated in HNSCC. In the HNSCC cohort of the TCGA dataset, miRNAs that were differentially expressed in high TMB and low TMB samples were screened. The least absolute contraction and selection operator (LASSO) method is used to construct a miRNA-based feature classifier to predict the TMB level in the training set. The test set is used to verify the classifier. The correlation between the miRNA-based classifier index and the expression of three immune checkpoints (PD1, PDL1, and CTLA4) was explored. We further perform functional enrichment analysis on the miRNA contained in the miRNA-based feature classifier. Twenty-five differentially expressed miRNAs are used to build miRNA-based feature classifiers to predict TMB levels. The accuracy of the 25-miRNA-based signature classifier is 0.822 in the training set, 0.702 in the test set, and 0.774 in the total set. The miRNA-based feature classifier index showed a low correlation with PD1 and PDL1, but no correlation with CTLA4. The enrichment analysis of these 25 miRNAs shows that they are involved in many immune-related biological processes and cancer-related pathways. The miRNA expression patterns are related to tumor mutation burden, and miRNA-based feature classifiers can be used as biomarkers to predict TMB levels in HNSCC.
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http://dx.doi.org/10.1155/2020/1686480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787755PMC
December 2020

Systemic inflammation and chronic kidney disease in a patient due to the RNASEH2B defect.

Pediatr Rheumatol Online J 2021 Jan 22;19(1). Epub 2021 Jan 22.

Department of Rheumatology and Immunology, Shenzhen Children's Hospital, 7019 Yitian Road, Shenzhen, 518038, China.

Introduction: Aicardi-Goutières (AGS) is a rare immune dysregulated disease due to mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1, or IFIH1. Clinical features include basal ganglia calcifications, white matter abnormalities, and cerebral atrophy. Severe systemic inflammation and chronic kidney disease (CKD) are extremely rare in AGS. Herein, we report a patient presenting with systemic inflammation and CKD to broaden the clinical phenotype spectrum of the RNASEH2B defect.

Methods: All testing and molecular genetic analysis were performed after obtaining the informed consent of the parents. Demographic, clinical, and laboratory findings were abstracted from outpatient and inpatient encounters. Cerebral magnetic resonance imaging (MRI), computed tomography (CT) scans, and renal biopsy histopathology reports were reviewed and summarized. Whole exome sequencing (WES) was performed on peripheral blood cells. After exposure to cGAMP in vitro for 24 h, mRNA expression of 12 IFN-stimulated cytokine genes in PBMCs was assessed. Serum cytokine levels were detected by Milliplex.

Results: A 11-year-old girl presented with recurrent aseptic fever, arthritis, chilblains, failure to thrive, mild hearing loss, and neurological manifestations. Laboratory and immunologic findings demonstrated lymphopenia, low complement levels, positive autoantibodies, elevated levels of acute-phase reactants and inflammatory cytokines. Cerebral imaging showed cerebral atrophy, white matter abnormalities, and intracranial calcification. Renal biopsy showed glomerular sclerosis in 3 of 14 glomeruli, infiltration of lymphocytes and other mononuclear cells. WES revealed a homozygous and heterozygous mutations in RNASEH2B. Over-expression of IFN-stimulated cytokine genes was observed, including IFI44, IFI27, IFIT1, IFIT2, IFIT3, ISG15, OAS1, and SIGLEC1.

Conclusions: To date, only two cases with AGS have been reported to have renal disease. Here, we describe a patient with both homozygous and heterozygous variants in RNASEH2B, presenting with neurological manifestations, persistently systemic autoinflammation, and CKD. CKD has never been reported in patients with AGS due to the RNASEH2B defect.

Trial Registration: Not applicable; this was a retrospective study.
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http://dx.doi.org/10.1186/s12969-021-00497-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821736PMC
January 2021

A multi-level hypoglycemia early alarm system based on sequence pattern mining.

BMC Med Inform Decis Mak 2021 Jan 21;21(1):22. Epub 2021 Jan 21.

Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, 200040, China.

Background: Early alarm of hypoglycemia, detection of asymptomatic hypoglycemia, and effective control of blood glucose fluctuation make a great contribution to diabetic treatment. In this study, we designed a multi-level hypoglycemia early alarm system to mine potential information in Continuous Glucose Monitoring (CGM) time series and improve the overall alarm performance for different clinical situations.

Methods: Through symbolizing the historical CGM records, the Prefix Span was adopted to obtain the early alarm/non-alarm frequent sequence libraries of hypoglycemia events. The longest common subsequence was used to remove the common frequent sequence for achieving the hypoglycemia early alarm in different clinical situations. Then, the frequent sequence pattern libraries with different risk thresholds were designed as the core module of the proposed multi-level hypoglycemia early alarm system.

Results: The model was able to predict hypoglycemia events in the clinical dataset of level-I (sensitivity 85.90%, false-positive 23.86%, miss alarm rate 14.10%, average early alarm time 20.61 min), level-II (sensitivity 80.36%, false-positive 17.37%, miss alarm rate 19.63%, average early alarm time 27.66 min), and level-III (sensitivity 78.07%, false-positive 13.59%, miss alarm rate 21.93%, average early alarm time 33.80 min), respectively.

Conclusions: The proposed approach could effectively predict hypoglycemia events based on different risk thresholds to meet different prevention and treatment requirements. Moreover, the experimental results confirm the practicality and prospects of the proposed early alarm system, which reflects further significance in personalized medicine for hypoglycemia prevention.
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http://dx.doi.org/10.1186/s12911-021-01389-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819198PMC
January 2021

The complete chloroplast genome sequence of (Ericaceae).

Mitochondrial DNA B Resour 2020 Aug 14;5(3):3168-3169. Epub 2020 Aug 14.

College of Forestry, Fujian Agriculture and Forestry University, Fuzhou, China.

is one of the representative plants of Ericaceae family, which was famous for entire translucent and 'ghostly' white. Also, unique lifestyle also attracts lots of researchers, which it obtains through fixed carbon from photosynthetic plants via a shared mycorrhizal network. In this study, the complete chloroplast (cp) genome of was assembled and annotated, its full-length is 26,913 bp. Plastid genome contains 31 genes, 14 protein-coding genes, 14 tRNA genes, and 3 rRNA genes. The phylogenetic analyses based on the complete chloroplast genome sequence provided solid evidence that has a close relationship The chloroplast genome presented here will help for further conservation of and other saprophytes.
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http://dx.doi.org/10.1080/23802359.2020.1806754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782332PMC
August 2020

Identification and validation of poor prognosis immunoevasive subtype of muscle-invasive bladder cancer with tumor-infiltrating podoplanin cell abundance.

Oncoimmunology 2020 04 3;9(1):1747333. Epub 2020 Apr 3.

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.

The choice of chemo- or immuno-therapy for muscle-invasive bladder cancer (MIBC) patients remains contentious. Podoplanin is newly identified as an immune checkpoint which intrigues us to explore the clinical significance and immunoregulatory role of tumor-infiltrating podoplanin cells (PDPN cells) in MIBC. A retrospective analysis of 259 MIBC patients from Zhongshan Hospital (n = 141) and Shanghai Cancer Center (n = 118) was conducted. A total of 406 MIBC patients from TCGA database were enrolled to investigate the relationship between PDPN and molecular characterization. We found that tumor-infiltrating PDPN cell abundance indicated an inferior overall survival and recurrence-free survival. pT2 MIBC patients with PDPN cell low infiltration could benefit more from adjuvant chemotherapy (ACT). Increased PDPN cell infiltration was associated with diminished GZMB and TNF-α expression while correlated with expanded PD-1, PD-L1, LAG-3 and TIM-3 expression and tumor-promoting regulatory T cell and M2 macrophage infiltration. Tumors with high PDPN mRNA expression mainly presented luminal-infiltrated and basal-squamous subtypes (2017 TCGA classification) or stroma-rich and Ba/Sq subtypes (consensus classification). Elevated PDPN mRNA expression was associated with less FGFR3 activation signature and more T-cell-inflamed signature and EGFR activation signature. In conclusion, tumor-infiltrating PDPN cells could be applied as an independent prognosticator for clinical outcome and a predictive biomarker for suboptimal ACT responsiveness, which was also associated with immunosuppressive contexture infiltration. Intratumoral PDPN expression had a correlation with MIBC molecular classification and therapy-related signatures. The novel immune checkpoint PDPN should be considered as a possible immunotherapeutic target for MIBC.
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http://dx.doi.org/10.1080/2162402X.2020.1747333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759386PMC
April 2020