Publications by authors named "Rong Xia"

176 Publications

RNA-binding protein RBM24 represses colorectal tumourigenesis by stabilising PTEN mRNA.

Clin Transl Med 2021 10;11(10):e383

Institute of Stem Cell and Regenerative Medicine, School of Medicine, Xiamen University, Xiamen, Fujian, People's Republic of China.

Background: RNA-binding motif protein 24 (RBM24) functions as a splicing regulator, which is critical for organ development and is dysregulated in human cancers. Here, we aim to uncover the biological function of RBM24 in colorectal tumourigenesis.

Methods: Xenograft tumour model, Rbm24 knockout and Apc mouse models were utilised. Colorectal cancer cells overexpressing or silencing RBM24 were established. RNA immunoprecipitation (RIP) assay was conducted to detect protein-RNA associations. Gene expression was measured by immunohistochemistry, western blotting, or quantitative PCR (qPCR).

Results: Rbm24-knockout mice developed spontaneous colorectal adenomas with lower expression of phosphatase and tensin homolog (PTEN). Immunohistochemical staining for the proliferation markers Ki-67 and pHH3 and BrdU assay showed intestinal hyperplasia in Rbm24-knockout mice compared to wild-type mice. RBM24 expression in colorectal adenoma tissues of Apc mouse was downregulated compared with adjacent normal samples and was positively correlated with PTEN expression. In vitro, RBM24 overexpression suppressed cell proliferation, migration, invasion and increased sensitivity to 5-FU or cisplatin in CRC cells. Mechanistically, RBM24 maintained PTEN mRNA stability by directly binding to the GT-rich region at positions 8101-8251 in the 3'-UTR of PTEN mRNA, prolonging the half-life of PTEN mRNA, thereby increasing PTEN expression. Hence, low expression of RBM24 downregulated PTEN mRNA, causing the activation of PI3K-Akt signalling in CRC cells. Furthermore, RBM24 expression in CRC tissues was lower than adjacent normal samples. RBM24 expression was positively correlated with PTEN expression and negatively correlated with Ki-67 level. CRC patients with high RBM24 expression had a favourable outcome.

Conclusions: Taken together, RBM24 expression is markedly lower in colorectal tumours than in para-carcinoma tissues. Rbm24-knockout mice develop spontaneous colorectal adenomas. RBM24 directly binds and stabilises PTEN mRNA, which could cause the suppression of CRC cell proliferation, migration and invasion, thereby repressing colorectal tumourigenesis. These findings support the tumour-suppressive role of RBM24. Targeting RBM24 holds strong promise for the diagnosis and treatment of CRC.
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http://dx.doi.org/10.1002/ctm2.383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8506628PMC
October 2021

Clinical characteristics and prognostic factors of cervical adenocarcinoma.

Asian J Surg 2021 Oct 21;44(10):1283-1285. Epub 2021 Sep 21.

Department of Gynecology, Cancer Hospital of China Medical University, Liaoning Province Cancer Hospital, Shenyang, 110042, China. Electronic address:

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http://dx.doi.org/10.1016/j.asjsur.2021.06.063DOI Listing
October 2021

Expression of Four Autophagy-Related Genes Accurately Predicts the Prognosis of Gastrointestinal Cancer in Asian Patients.

Dis Markers 2021 25;2021:7253633. Epub 2021 Aug 25.

Key Lab of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, China.

Gastrointestinal (GI) cancers are among the most fatal diseases in the world. Numerous studies have demonstrated the relationship between autophagy and development of gastrointestinal cancers. However, whether autophagy-related genes can predict prognosis of GI cancers in individuals of Asian ancestry has not been defined. This study, evaluated the prognostic value of autophagy-related genes in gastrointestinal cancer. Expression profile of autophagy-related genes for 296 gastrointestinal cancer patients of Asian ancestry was downloaded from the TCGA database (TCGA-LIHC, TCGA-STAD, TCGA-ESCA, TCGA-PAAD, TCGA-COAD, TCGA-CHOL, and TCGA-READ). The prognostic value of the autophagy-related genes was evaluated using univariate Cox, LASSO, and multivariate Cox regression analyses. The risk score of the autophagy-related gene signature was calculated to assess its predictive prognostic value for GI cancers. Forty-seven differentially expressed autophagy-related genes, in Asian patients with gastrointestinal cancers, were identified. Of the 47 genes, 4 were associated with prognosis of GI cancer (SQSTM1, BIRC5, NRG3, and CXCR4). A prognostic model for GI cancer, based on the expression of the above 4 genes in the training set, showed that cancer patients were stratified into high-risk and low-risk groups ( < 0.05). The utility of the model for overall survival (OS) of GI cancer patients was consistent across the entire set, training set, and test set (entire set: = 4.568 × 10; train set: = 5.718 × 10; test set: = 3.516 × 10). The sensitivity and specificity of the ROC curve of the above prognostic model in predicting the 5-year prognosis of GI cancer was satisfactory (entire set: 0.728; train set: 0.727; test set: 0.733). Analysis of clinical samples validated the overexpression of the 4 genes (SQSTM1, BIRC5, NRG3, and CXCR4) in tumor tissues relative to paired normal tissues, consistent with bioinformatic findings. Expression of the 4 autophagy-related genes (SQSTM1, BIRC5, NRG3, and CXCR4) can accurately predict the prognosis of gastrointestinal tumors in Asian patients.
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http://dx.doi.org/10.1155/2021/7253633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413069PMC
August 2021

Follicular dendritic cell sarcoma of the cervical lymph node diagnosed on fine needle aspiration cytology.

Cytopathology 2021 Aug 5. Epub 2021 Aug 5.

Department of Pathology, New York University Langone Health, New York, NY, USA.

Follicular dendritic cell sarcomas (FDCS) are rare tumours of lymph nodes and extranodal tissues which are grouped with the histiocytic and dendritic cell neoplasms. The diagnosis is usually made after thorough clinical and pathological examination with immunohistochemical analysis. Difficulties persist in diagnosing FDCS on cytological preparations. We report herein a case of a 57-year-old female who presented with a right neck mass of 5 months duration. Computed Tomography (CT) imaging of the neck reported a necrotic right level IIb lymph node and asymmetric fullness of the right palatine tonsil. Fine needle aspiration (FNA) biopsy revealed numerous spindle, oval and stellate neoplastic cells, arranged singly and in syncytia with moderate nuclear pleomorphism, vesicular chromatin pattern, and prominent nucleoli, sprinkled with small lymphocytes. The tumour cells were strongly diffusely positive for CD21, CD23, and D2-40 immunostaining on cell bock sections, but were negative for CD1a and CD34, supporting the diagnosis of FDCS. Follow-up surgical pathology on the resection showed histopathological features and an immunohistochemical profile consistent with FDCS.
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http://dx.doi.org/10.1111/cyt.13047DOI Listing
August 2021

Incubation trial indicated the earthworm intestinal bacteria as promising biodigestor for mitigating tetracycline resistance risk in anthropogenic disturbed forest soil.

Sci Total Environ 2021 Dec 30;798:149337. Epub 2021 Jul 30.

Soil Ecology Lab, College of Resources and Environmental Science, Nanjing Agricultural University, Nanjing 210095, China; Key Laboratory of Plant Immunity, Jiangsu Collaborative Center for Solid Organic Waste Resource Utilization, Nanjing Agricultural University, Nanjing 210095, China.

The continuous input of antibiotics due to frequent anthropogenic activities have increased the dissemination risk of antibiotic resistance genes (ARGs) in forest soil. As soil engineers, it remains unclear whether earthworm intestinal microbial communities might play a role in controlling the ARG proliferation in forest soil. This study collected forest soil in the Yangtze River Delta, China, and its resident Metaphire guillelmi to investigate the interaction between tetracycline (50 μg kg) and the bacteria in worm gut and soil. Metagenome sequencing analysis indicated that the abundance of the total ARGs in both the soil (S2) and the worm gut (E2) was 1.3 (p < 0.001) and 1.2 (p < 0.001) times higher than the soil (S1) and (E1) without tetracycline exposure; and under tetracycline stress, the relative abundance of 36 and 20 bacterial genera in forest soil and worm gut were significantly increased respectively. However, the ARGs/ARB abundance decreased in the soil with the worm addition than that without, which may be related to the fact that earthworm intestinal bacteria harbored more tetracycline-degrading genes, i.e. dehydrogenase genes adh, ETFDH, and gpr, etc. Structural equation model analysis indicated that bacteria in worm intestinal has stronger ability to degrade tetracycline than in soil, and the main dissipate way was dehydrogenation. Together, the results contributed to understanding the promising role of worm intestinal bacteria in controlling the ARG risk caused by antibiotic disturbed forest soil.
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http://dx.doi.org/10.1016/j.scitotenv.2021.149337DOI Listing
December 2021

Melanoidins, extracted from Chinese traditional vinegar powder, inhibit alcohol-induced inflammation and oxidative stress in macrophages via activation of SIRT1 and SIRT3.

Food Funct 2021 Sep 21;12(17):8120-8129. Epub 2021 Jul 21.

College of Food Science and Nutritional Engineering, China Agricultural University, Beijing Key Laboratory of Functional Food from Plant Resources, Beijing, 100083, China.

Alcohol induces inflammation and oxidative stress with the dysregulation of proinflammatory cytokines, which are implicated in the pathogenesis of alcoholic liver injury. Melanoidins are known to exert an antioxidant effect, however, their function in inhibiting alcohol-induced inflammation is unclear. In this study, we examined the role of melanoidins from Chinese traditional vinegar powder in terms of their anti-inflammatory and antioxidant properties in RAW 264.7 macrophages and elucidated their mechanisms of function. In macrophages, melanoidins significantly suppress the mRNA expression of interleukin (Il)-6, Il-1β and tumor necrosis factor α (Tnf-α) with a concomitant inhibitory effect on IL-1β, IL-6 and TNFα secretion, which are increased by ethanol. In addition, ethanol significantly increases the cellular reactive oxygen species (ROS) levels and the expression of cytochrome β-245 and beta polypeptide (Cybb), which are repressed by melanoidins to basal level. However, the expression of genes related to oxidative stress significantly decreases in response to ethanol, while it is significantly increased by melanoidins. Importantly, treatment with ethanol led to significant decreases in SIRT1 and SIRT3 transcription, translation, and activation, as well as the nicotinamide adenine dinucleotide (NAD) levels. Interestingly, all the decreases were markedly attenuated by melanoidins. Ethanol promoted the expression of proinflammatory genes, whereas coincubation with resveratrol (a potent SIRT agonist) inhibited this effect. Conversely, the addition of sirtinol (a known SIRT inhibitor) augmented the proinflammatory gene expression. Taken together, our findings suggest that melanoidins exert anti-inflammatory and antioxidant functions via abolishing decreases in SIRT1 and SIRT3 expression and cellular NAD levels in ethanol-induced macrophages and may serve as a new therapeutic agent for the prevention of alcohol-induced cell damage.
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http://dx.doi.org/10.1039/d1fo00978hDOI Listing
September 2021

Perioperative Transfusion is Related to the Length of Hospital Stays in Primary Liver Cancer Patients.

Cancer Manag Res 2021 21;13:4947-4954. Epub 2021 Jun 21.

Department of Transfusion Medicine, Huashan Hospital, Fudan University, Shanghai, 200040, People's Republic of China.

Purpose: Blood loss may be corrected with red blood cell transfusion, but may ultimately contribute to negative impacts. This study was a retrospective analysis to assess the impact of perioperative blood transfusion on hospital stay days in liver cancer patients.

Methods: We retrospectively examined data from patients with primary liver cancer who underwent curative resection. Patients were divided into perioperative blood transfusion (PBT) and non-PBT groups. Data were given as means and SDs for continuous variables and as counts and percentage for categorical variables. The correlation between blood transfusion and hospital stay days was analyzed by Fisher's exact test. Multivariable logistic regression analyses were used to identify independent predictors of length of hospital stays.

Results: Totally 206/1031 patients (20.3%) were given perioperative transfusion. The mean length of hospital stay was 17.8 days in PBT and 13.9 days in non-PBT groups. Our multivariable logistic regression showed transfusion, total bilirubin, indirect bilirubin, and the ratio of albumin to bilirubin were all indicators of the length of hospital stay days. Perioperative transfusion was also associated with prolonged length of hospital stays (95% CI: 0.395-0.811, p = 0.002). Transfusion also affected intrinsic coagulation factors (activated partial thromboplastin time, fibrinogen, platelet), inflammatory index (neutrocyte to lymphocyte ratio, monocyte), albumin and bilirubin levels.

Conclusion: Perioperative transfusion of blood was associated with a significantly increased length of hospital stays probably via changing intrinsic coagulation and inflammatory factors and bilirubin levels in plasma.
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http://dx.doi.org/10.2147/CMAR.S296022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233480PMC
June 2021

Gynaecological perivascular epithelioid cell tumour (PEComa): comparative analysis of proposed algorithms for prediction of clinical outcome.

Histopathology 2021 Nov 3;79(5):847-860. Epub 2021 Sep 3.

NYU Langone Medical Center, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Aims: Perivascular epithelioid cell tumours (PEComas) are rare mesenchymal tumours that coexpress smooth muscle and melanocytic markers. They have a predilection for gynaecological organs, where they present a unique diagnostic challenge, because of morphological and immunohistochemical overlap with more common smooth muscle and stromal tumours. Limited information regarding the natural history, owing to the rarity of this tumour, makes accurate risk stratification difficult. We aimed to review clinicopathological features of gynaecological PEComa and compare accuracy of five different classification systems for prediction of prognosis.

Methods And Results: We have described the clinicopathological features of 13 new cases and tested five prognostic algorithms in a total of 67 cases of gynaecological PEComa. Receiver operating characteristic curves were constructed and areas under the curve (AUCs) were calculated to evaluate predictive accuracy. The modified gynaecological-specific algorithm showed high sensitivity and specificity and yielded the highest AUC (0.864). It's earlier version, the gynaecological-specific algorithm, suffered from lower specificity (AUC = 0.843). The post-hoc McNemar test confirmed significant differences between the performances of the modified gynaecological-specific algorithm and the gynaecological-specific algorithm (P = 0.008). The original Folpe algorithm for PEComas of all sites showed low specificity, had a lower AUC (0.591), and was inapplicable in 18% of cases. Its two later versions (the revised Folpe algorithm and the modified Folpe algorithm) also yielded lower AUCs (0.690 and 0.591, respectively).

Conclusion: We have shown that the modified gynaecological-specific algorithm predicts the clinical outcome of gynaecological PEComa with high accuracy, and have validated its use for prognostic stratification of gynaecological PEComa.
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http://dx.doi.org/10.1111/his.14434DOI Listing
November 2021

Metagenomic sequencing reveals detoxifying and tolerant functional genes in predominant bacteria assist Metaphire guillelmi adapt to soil vanadium exposure.

J Hazard Mater 2021 08 18;415:125666. Epub 2021 Mar 18.

Soil Ecology Lab, College of Resources and Environmental Science, Nanjing Agricultural University, Nanjing 210095, China.

Due to extensive vanadium (V) mining and processing, an increasing amount of V has accumulated in soil, which poses a threat to public health. Consequently, we used earthworm (Metaphire guillelmi) incubation trials in V-contaminated soil (0-300 mg kg) to explore the response of soil indigenous bacteria and earthworm intestinal bacteria to V stress. Metagenomic analysis revealed that V exposure changed the bacterial composition in the soil and the worm gut. However, although the core species varied between soil and worm gut, the two systems shared the predominant bacteria, including Staphylococcus, Nocardioides, Streptococcus, and Nitrosopumilales. Two functional genotypes were detected in the shared core species, i.e., reductive genes and resistant genes. The reductive genes mainly consisted of those involved in glutathione, cysteine, methionine, sulfur, and nitrogen metabolisms. The resistant genes included those encoding the oxidation damage repair system, the outer membrane protein, the antioxidant enzyme system, the metal-binding, and the heavy-metal efflux. Therefore, the shared core species exert a comprehensive strategy to survive V stress involving the alliance of heavy metal detoxifying and tolerant genes. This study provides novel information about the detoxification mechanisms of bacterial populations in soil and worm gut to survive V stress.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125666DOI Listing
August 2021

Brucella Outer Membrane Lipoproteins 19 and 16 Differentially Induce IL-18 Response or Pyroptosis in Human Monocytic Cells.

J Infect Dis 2021 May 20. Epub 2021 May 20.

Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, China.

Background: Brucella species (B. spp.) are Gram-negative intracellular bacteria, causing severe inflammatory diseases in animals and humans. Two major lipoproteins (L19) and (L16) of Brucella outer membrane proteins (OMPs) were extensively explored in associating with inflammatory response of human monocytes (THP-1).

Methods: Activated THP-1 cells induced with recombinant L19 and L16 were analyzed in comparison with unlipidated forms (U19 and U16) and lipopolysaccharide (LPS) of B. melitensis, respectively.

Results: Secretion of inflammatory factors TNF-α, IL-6 and IL-1β was significantly increased from L19, L16 or both stimulated THP-1 cells. High secretion of IL-18 was detected only from L19-induced cells. Signaling of those cytokine responses was identified mainly through P38-MAPK pathway, and signaling of L19-induced IL-1β response was partly occurred via NF-κB. Exploration for different forms of IL-18 found that L19-induced production of active IL-18 (18 kD) was through up-regulating NLRP3 and activating caspase-1, while L16-induced production of inactive IL-18 fragments (15 kD and 16 kD) occurred through activating caspase-8/3. Additionally, L19 up-regulated phosphorylation of XIAP for inhibiting caspase-3 activity to cleave IL-18, while L16 activated caspase-3 for producing GSDME-N and leading to pyroptosis of THP-1 cells.

Conclusion: Brucella L19 and L16 differentially induce IL-18 response or pyroptosis in THP-1 cells, respectively.
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http://dx.doi.org/10.1093/infdis/jiab272DOI Listing
May 2021

2-Mercaptoethanol (2-ME)-based IATs or Polybrene method mitigates the interference of daratumumab on blood compatibility tests.

Hematology 2021 Dec;26(1):365-370

Department of Blood Transfusion, Changzheng Hospital, Naval Medical University, Shanghai, People's Republic of China.

Objectives: Treating red blood cells (RBCs) with dithiothreitol (DTT) is a wildly-recommended to overcome the interference of the daratumumab (DARA) with blood compatibility testing. Nevertheless, DTT can be hard to obtain in the clinical laboratory, while its use in routine practice may be time-consuming. In the following study, we explored the feasibility of using a commercial 2-mercaptoethanol (2-ME) working solution or the time-saving Polybrene method to mitigate DARA interference.

Methods: Antibody screening and cross-matching were performed using 2-ME or DTT-based indirect antiglobulin tests (IATs) and Polybrene method (with human IgG anti-E same IATs titer as DARA as positive control) on 37 samples. Most clinically important blood group antigens on RBCs were detected after treatment with 2-ME or DTT.

Results: Treating RBCs with 2-ME eliminates the DARA interference with the antibody screening or cross-matching; yet, K antigen is denatured during treatment. DARA does not interfere with antibody screening and cross-matching via Polybrene method, while 2+ agglutinations of anti-E antibody with the same titer (IATs method) as DARA could be observed in the positive controls via this method.

Conclusion: 2-ME-based IATs or Polybrene method could replace DTT-based IATs to mitigate DARA interference.
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http://dx.doi.org/10.1080/16078454.2021.1918916DOI Listing
December 2021

Vitamin D/VDR Protects Against Diabetic Kidney Disease by Restoring Podocytes Autophagy.

Diabetes Metab Syndr Obes 2021 16;14:1681-1693. Epub 2021 Apr 16.

Three Gorges University College of Medical Science, Yichang, 443000, People's Republic of China.

Objective: The present study is to investigate the effect of vitamin D/Vitamin D Receptor (VDR) signaling on podocyte autophagy in diabetic nephropathy.

Methods: Kidney tissue sections from patients with diabetic nephropathy and nontumor kidney were checked under electronic microscope and VDR immunohistochemistry. Diabetic rat models were induced by intraperitoneal injection of streptozotocin (STZ) (60 mg/kg). Calcitriol treatment was achieved by gavage at dose of 0.1μg/kg/d. Blood, urine and kidney tissue specimens were used for serum, urine biochemistry, histopathology and molecular biology testing. Podocyte cell line MPC-5 was cultured under hyperglycaemic conditions in the absence or presence of 100 nmol/L calcitriol to investigate podocyte injury and autophagy.

Results: VDR and autophagosomes in podocytes were significantly decreased in renal biopsy from patients with diabetic nephropathy, compared to healthy kidney tissue. Rats with STZ treatment developed typical diabetic kidney disease with low VDR expression. Calcitriol, the active form of vitamin D, could activate VDR and attenuate diabetic nephropathy including proteinuria and glomerular sclerosis. Calcitriol treatment also alleviated the podocyte foot process fusion, reduced podocyte injury marker desmin and preserved slit diaphragms proteins in diabetic nephropathy. Reduced LC3II/I, Beclin-1 and elevated p62 in renal homogenate and reduced autophagosomes and LC3II in podocytes indicated podocytes autophagy impairment in diabetic nephropathy. Whereas calcitriol treatment restored podocyte autophagy activities. In cultured podocytes, the protective effect of calcitriol against high glucose induced podocyte injury could be abated by autophagy inhibitor chloroquine.

Conclusion: Our study delivered the evidence that calcitriol/VDR signaling attenuated diabetic nephropathy and podocytes injury by restoring podocytes autophagy. This finding may have potential implication for exploring protective mechanisms of calcitriol/VDR in diabetic nephropathy.
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http://dx.doi.org/10.2147/DMSO.S303018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057803PMC
April 2021

MicroLet-7b Regulates Neutrophil Function and Dampens Neutrophilic Inflammation by Suppressing the Canonical TLR4/NF-κB Pathway.

Front Immunol 2021 29;12:653344. Epub 2021 Mar 29.

Department of Blood Transfusion, Huashan Hospital, Fudan University, Shanghai, China.

Sepsis is a heterogeneous syndrome caused by a dysregulated host response during the process of infection. Neutrophils are involved in the development of sepsis due to their essential role in host defense. COVID-19 is a viral sepsis. Disfunction of neutrophils in sepsis has been described in previous studies, however, little is known about the role of microRNA-let-7b (miR-let-7b), toll-like receptor 4 (TLR4), and nuclear factor kappa B (NF-κB) activity in neutrophils and how they participate in the development of sepsis. In this study, we investigated the regulatory pathway of miR-let-7b/TLR4/NF-κB in neutrophils. We also explored the downstream cytokines released by neutrophils following miR-let-7b treatment and its therapeutic effects in cecal ligation and puncture (CLP)-induced septic mice. Six-to-eight-week-old male C57BL/6 mice underwent CLP following treatment with miR-let-7b agomir. Survival (n=10), changes in liver and lungs histopathology (n=4), circulating neutrophil counts (n=4), the liver-body weight ratio (n=4-7), and the lung wet-to-dry ratio (n=5-6) were recorded. We found that overexpression of miR-let-7b could significantly down-regulate the expression of human-derived neutrophilic TLR4 at a post-transcriptional level, a decreased level of proinflammatory factors including interleukin-6 (IL-6), IL-8, tumor necrosis factor α (TNF-α), and an upregulation of anti-inflammatory factor IL-10 . After miR-let-7b agomir treatment , neutrophil recruitment was inhibited and thus the injuries of liver and lungs in CLP-induced septic mice were alleviated (p=0.01 and p=0.04, respectively), less weight loss was reduced, and survival in septic mice was also significantly improved (p=0.013). Our study suggested that miR-let-7b could be a potential target of sepsis.
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http://dx.doi.org/10.3389/fimmu.2021.653344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044834PMC
May 2021

LHPP-Mediated Histidine Dephosphorylation Suppresses the Self-Renewal of Mouse Embryonic Stem Cells.

Front Cell Dev Biol 2021 16;9:638815. Epub 2021 Mar 16.

Institute of Stem Cell and Regenerative Medicine, School of Medicine, Xiamen University, Xiamen, China.

Self-renewal of embryonic stem cells (ESCs) is orchestrated by a vast number of genes at the transcriptional and translational levels. However, the molecular mechanisms of post-translational regulatory factors in ESC self-renewal remain unclear. Histidine phosphorylation, also known as hidden phosphorylation, cannot be detected by conventional experimental methods. A recent study defined phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) as a histidine phosphatase, which regulates various biological behaviors in cells via histidine dephosphorylation. In this study, the doxycycline (DOX)-induced hLHPP-overexpressing mouse ESCs and mouse LHPP silenced mESCs were constructed. Quantitative polymerase chain reaction (qPCR), western blotting analysis, immunofluorescence, Flow cytometry, colony formation assays, alkaline phosphatase (AP) and bromodeoxyuridine (Brdu) staining were performed. We found that the histidine phosphorylation level was strikingly reduced following LHPP overexpression. Besides, the expression of and , indispensable genes in the process of ESCs self-renewal, was significantly down-regulated, while markers related to the differentiation were markedly elevated. Moreover, LHPP-mediated histidine dephosphorylation induced GG phase arrest in mESCs, suggesting LHPP was implicated in cell proliferation and cell cycle. Conversely, silencing of promoted the self-renewal of mESCs and reversed the RA induced increased expression of genes associated with differentiation. Mechanistically, our findings suggested that the enzymatic active site of LHPP was the cysteine residue at position 226, not 53. LHPP-mediated histidine dephosphorylation lowered the expression levels of β and the cell cycle-related genes and , while it up-regulated the cell cycle suppressor genes and . Taken together, our findings reveal that LHPP-mediated histidine dephosphorylation plays a role in the self-renewal of ESCs. LHPP-mediated histidine dephosphorylation inhibited the self-renewal of ESCs by negatively regulating the Wnt/β-catenin pathway and downstream cell cycle-related genes, providing a new perspective and regulatory target for ESCs self-renewal.
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http://dx.doi.org/10.3389/fcell.2021.638815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007871PMC
March 2021

Electrochemical reduction of acetonitrile to ethylamine.

Nat Commun 2021 03 29;12(1):1949. Epub 2021 Mar 29.

Center for Catalytic Science and Technology, Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE, United States.

Electrifying chemical manufacturing using renewable energy is an attractive approach to reduce the dependence on fossil energy sources in chemical industries. Primary amines are important organic building blocks; however, the synthesis is often hindered by the poor selectivity because of the formation of secondary and tertiary amine byproducts. Herein, we report an electrocatalytic route to produce ethylamine selectively through an electroreduction of acetonitrile at ambient temperature and pressure. Among all the electrocatalysts, Cu nanoparticles exhibit the highest ethylamine Faradaic efficiency (~96%) at -0.29 V versus reversible hydrogen electrode. Under optimal conditions, we achieve an ethylamine partial current density of 846 mA cm. A 20-hour stable performance is demonstrated on Cu at 100 mA cm with an 86% ethylamine Faradaic efficiency. Moreover, the reaction mechanism is investigated by computational study, which suggests the high ethylamine selectivity on Cu is due to the moderate binding affinity for the reaction intermediates.
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http://dx.doi.org/10.1038/s41467-021-22291-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007591PMC
March 2021

Identification of common genetic variants associated with serum concentrations of p, p'-DDE in non-occupational populations in eastern China.

Environ Int 2021 07 20;152:106507. Epub 2021 Mar 20.

Key Lab of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, PR China; State Key Lab of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, PR China. Electronic address:

Dichlorodiphenyldichloroethylene (DDE) is the major and most stable toxic metabolite of dichlorodiphenyltrichloroethane (DDT), a well-known organochlorine pesticide banned worldwide in the 1980s. However, it remains easy to detect in humans, and internal levels vary widely among individuals. In the present study, a genome-wide association study (GWAS) (511 subjects) and two replications (812 and 1030 subjects) were performed in non-occupational populations in eastern China. An estimated dietary intake (EDI) of p, p'-DDT and p, p'-DDE was calculated by a food frequency questionnaire (FFQ) and the determination of 195 food and 85 drinking water samples. In addition, functional verifications of susceptible loci were performed by dual-luciferase reporter, immunoblotting and metabolic activity assays in vitro. p, p'-DDT and p, p'-DDE were measured using gas chromatography-tandem mass spectrometry (GC-MS/MS). A common loci rs3181842 (high linkage equilibrium with rs2279345) in CYP2B6 at 19p13.2 were found to be strongly associated with low serum levels of p, p'-DDE in this population in GWAS and were verified by two replications and combined analysis of 2353 subjects (P = 1.00 × 10). In addition, p, p'-DDE levels were significantly lower in subjects with the rs3181842 C allele than in those carrying the normal genotype, even in individuals with similar EDIs of p, p'-DDT. Furthermore, the rs3181842 C allele functionally led to low CYP2B6 expression and activity, resulting in a low metabolic capacity for the formation of p, p'-DDE from p, p'-DDT. The study highlighted that CYP2B6 variants were more relevant than environmental exposure to internal p, p'-DDE exposure, which is important information for DDT risk assessments.
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http://dx.doi.org/10.1016/j.envint.2021.106507DOI Listing
July 2021

Prognostic value of a novel glycolysis-related gene expression signature for gastrointestinal cancer in the Asian population.

Cancer Cell Int 2021 Mar 4;21(1):154. Epub 2021 Mar 4.

Key Lab of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211166, People's Republic of China.

Background: Globally, gastrointestinal (GI) cancer is one of the most prevalent malignant tumors. However, studies have not established glycolysis-related gene signatures that can be used to construct accurate prognostic models for GI cancers in the Asian population. Herein, we aimed at establishing a novel glycolysis-related gene expression signature to predict the prognosis of GI cancers.

Methods: First, we evaluated the mRNA expression profiles and the corresponding clinical data of 296 Asian GI cancer patients in The Cancer Genome Atlas (TCGA) database (TCGA-LIHC, TCGA-STAD, TCGA-ESCA, TCGA-PAAD, TCGA-COAD, TCGA-CHOL and TCGA-READ). Differentially expressed mRNAs between GI tumors and normal tissues were investigated. Gene Set Enrichment Analysis (GSEA) was performed to identify glycolysis-related genes. Then, univariate, LASSO regression and multivariate Cox regression analyses were performed to establish a key prognostic glycolysis-related gene expression signature. The Kaplan-Meier and receiver operating characteristic (ROC) curves were used to evaluate the efficiency and accuracy of survival prediction. Finally, a risk score to predict the prognosis of GI cancers was calculated and validated using the TCGA data sets. Furthermore, this risk score was verified in two Gene Expression Omnibus (GEO) data sets (GSE116174 and GSE84433) and in 28 pairs of tissue samples.

Results: Prognosis-related genes (NUP85, HAX1, GNPDA1, HDLBP and GPD1) among the differentially expressed glycolysis-related genes were screened and identified. The five-gene expression signature was used to assign patients into high- and low-risk groups (p < 0.05) and it showed a satisfactory prognostic value for overall survival (OS, p = 6.383 × 10). The ROC curve analysis revealed that this model has a high sensitivity and specificity (0.757 at 5 years). Besides, stratification analysis showed that the prognostic value of the five-gene signature was independent of other clinical characteristics, and it could markedly discriminate between GI tumor tissues and normal tissues. Finally, the expression levels of the five prognosis-related genes in the clinical tissue samples were consistent with the results from the TCGA data sets.

Conclusions: Based on the five glycolysis-related genes (NUP85, HAX1, GNPDA1, HDLBP and GPD1), and in combination with clinical characteristics, this model can independently predict the OS of GI cancers in Asian patients.
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http://dx.doi.org/10.1186/s12935-021-01857-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934443PMC
March 2021

Sclerosing encapsulating peritonitis presenting with paroxysmal abdominal pain and strangulated mechanical bowel obstruction: A case report.

Medicine (Baltimore) 2021 Feb;100(8):e24794

Key Lab of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health.

Rationale: Sclerosing encapsulated peritonitis (SEP) is a rare chronic peritoneal inflammation with unknown etiology, and is also known as abdominal cocoon. This occurs when the intestinal annulus is enveloped in the peritoneal cavity, resulting in intestinal obstruction. Its preoperative diagnosis and treatment strategy remains a challenge.

Patient Concerns: The study reports a 53-year-old male, who presented with a 4-day history of paroxysmal abdominal pain, without the adverse reaction of nausea, vomiting, or diarrhea.

Diagnosis: The accurate diagnosis of SEP was made after the emergency diagnostic laparoscopy.

Interventions: The laparoscopic exploration revealed that the small intestine was wrapped by a layer of peritoneum. Then, the abdominal fibrous membrane was removed surgically, and adhesiolysis were performed. The patient recovered well, and gradually recovered by the 10th post-operative day.

Outcomes: The patient was discharged uneventfully after 10 days, and the patient recovered well. After the 12-month follow-up, no symptoms of recurrence or complications were observed.

Lessons: The preoperative diagnosis of SEP remains difficult, and the onset of SEP has exhibited a younger trend. The diagnosis of SEP should remain on the list of differential diagnosis for paroxysmal abdominal pain. single-photon emission computed tomography/computed tomography and laparoscopic exploration have been proven to be helpful for establishing the diagnosis. In the early stage of intestinal obstruction caused by SEP, surgical intervention was immediately carried out in emergency department, and the patient recovered well after the operation. The present study also presents a review of the literature for other cases of SEP. The external evidence was helpful in making clinical decisions for patient care.
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http://dx.doi.org/10.1097/MD.0000000000024794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909216PMC
February 2021

Structural insight reveals SARS-CoV-2 ORF7a as an immunomodulating factor for human CD14 monocytes.

iScience 2021 Mar 12;24(3):102187. Epub 2021 Feb 12.

Molecular Imaging Center, Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China.

Dysregulated immune cell responses have been linked to the severity of coronavirus disease 2019 (COVID-19), but the specific viral factors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were currently unknown. Herein, we reveal that the Immunoglobulin-like fold ectodomain of the viral protein SARS-CoV-2 ORF7a interacts with high efficiency to CD14 monocytes in human peripheral blood, compared to pathogenic protein SARS-CoV ORF7a. The crystal structure of SARS-CoV-2 ORF7a at 2.2 Å resolution reveals three remarkable changes on the amphipathic side of the four-stranded β-sheet, implying a potential functional interface of the viral protein. Importantly, SARS-CoV-2 ORF7a coincubation with CD14 monocytes triggered a decrease in HLA-DR/DP/DQ expression levels and upregulated significant production of proinflammatory cytokines, including IL-6, IL-1β, IL-8, and TNF-α. Our work demonstrates that SARS-CoV-2 ORF7a is an immunomodulating factor for immune cell binding and triggers dramatic inflammatory responses, providing promising therapeutic drug targets for pandemic COVID-19.
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http://dx.doi.org/10.1016/j.isci.2021.102187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879101PMC
March 2021

Prevalence and evolutionary analyses of human T-cell lymphotropic virus in Guangdong province, China: Transcontinental and Japanese subtype lineages dominate the prevalence.

PLoS Negl Trop Dis 2021 02 4;15(2):e0009043. Epub 2021 Feb 4.

Guangzhou Blood Center, Guangdong, China.

To systematically characterize the prevalence and evolution of human T-cell lymphotropic virus (HTLV) infection among voluntary blood donors (BDs) in Guangdong province, China. A three-year survey for HTLV epidemiology among BDs was performed in Guangdong during 2016-2018. Anti-HTLV-1/2 was screened by ELISA and ECLIA, and subsequently confirmed by western blot (WB) and nucleic acid testing (NAT). The prevalence of HTLV in donors from different cities was calculated. The identified HTLV-positive cases were phylogenetically genotyped and analyzed in a Bayesian phylogenetic framework. Among 3,262,271 BDs, 59 were confirmed positive for HTLV-1 (1.81 per 100,000) and no HTLV-2 infection was found. The prevalence of HTLV-1 varied significantly among 21 cities in Guangdong province, China. The highest prevalence was found in donors from Shanwei (13.94 per 100,000), which is a coastal city in eastern Guangdong. Viral genomic sequences genotyped from 55 HTLV-1 carriers showed that 39 were transcontinental subtype and 16 were Japanese subtype. Specially, 13 out of 39 transcontinental subtype sequences were characterized with L55P mutation and 21 out of 55 sequences were characterized with L19F mutation in viral gp46 protein. The L55P mutation seemed be specific to eastern Asia since it only presented in the sequences from Japan, mainland China, and Taiwan. Phylogenetic analysis of gp46 gene shows that HTLV-1a may have been introduced to Guangdong through four different introduction events and formed major transmission clusters: clades I(13,602 years ago), II(16, 010 years ago), III(15,639 years ago) and IV(16,517 years ago). In general, Guangdong is considered to be a low-prevalence region for HTLV-1 infection, but the prevalence is significantly higher in Shanwei city. Transcontinental and Japanese subtype lineages dominate the prevalence in Guangdong. In terms of blood safety, HTLV antibody screening for first-time blood donors can effectively reduce the risk of HTLV transmission.
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http://dx.doi.org/10.1371/journal.pntd.0009043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888662PMC
February 2021

Gabapentin for phantom limb pain after amputation in pediatric oncology: a systematic review protocol.

Syst Rev 2021 01 13;10(1):26. Epub 2021 Jan 13.

Department of Internal Medicine (Pain Clinic), Cancer Hospital of China Medical University, No. 44 Xiaoheyan Road, Dadong District, Shenyang, 110042, China.

Background: Phantom limb pain (PLP) is a prevalent problem for children after amputation because of the chemotherapy treatment. Gabapentin is a potential option to manage PLP after amputation in pediatric oncology. However, no systematic review specifically investigated this topic. Thus, this study aims to appraise the efficacy and safety of gabapentin for post-amputation PLP in pediatric oncology.

Methods: Electronic databases (Cochrane Library, MEDLINE, EMBASE, Web of Science, CINAHL, PsychINFO, Scopus, WANGFANG, and Chinese Biomedical Literature Database) will be systematically searched from the beginning to the present without limitations to publication status and language. Primary outcome is pain intensity. Secondary outcomes are analgesic drug consumption, sleep quality, depression, anxiety, health-related quality of life, and adverse events. The treatment effect of all dichotomous outcome data will be estimated as risk ratio and 95% confidence intervals (CIs) and that of continuous outcome data will be calculated as mean difference or standardized mean difference and 95% CIs. Methodological quality of randomized controlled trials (RCTs) will be assessed using Cochrane risk of bias tool and that of case-controlled studies (CCSs) will be appraised using Newcastle-Ottawa Tool. Statistical analysis will be conducted using RevMan 5.3 software.

Discussion: This study will summarize up-to-date high-quality RCTs and CCSs to assess the efficacy and safety of gabapentin for PLP after amputation in pediatric oncology. The findings of this study will help to determine whether or not gabapentin is effective and safe for children with PLP after amputation.

Systematic Review Registration: INPLASY202060090.
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http://dx.doi.org/10.1186/s13643-020-01571-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807458PMC
January 2021

Seroprevalence of human T-lymphotropic virus infection among blood donors in China: a first nationwide survey.

Retrovirology 2021 01 7;18(1). Epub 2021 Jan 7.

National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.

Background: So far, the prevalence of human T-lymphotropic virus (HTLV) type 1 and 2 in some highly populated countries such as China is still unknown. In this study, a multi-center nationwide serological survey was designed and performed, to reveal the seroprevalence of HTLV infection among Chinese blood donors.

Results: Among 8,411,469 blood donors from 155 blood establishments, 435 were finally confirmed as HTLV carriers. The prevalence of HTLV infection in China varied in different provinces: Fujian had the highest prevalence of 36.240/100,000 (95% CI 31.990-41.050) and eleven provinces did not find HTLV-seropositive donors in the three years. no HTLV-2 infection was found. The overall prevalence of HTLV-1 in China decreased from 2016 to 2018. Female was identified as an independent risk factor of HTLV infection in China. Besides, seroconversion was observed in two of seven seroindeterminate donors 85 and 250 days after their last donation, respectively.

Conclusions: The seroprevalence of HTLV infection in most areas of China among blood donors is quite low, but it varies significantly in different geographic areas. Screening anti-HTLV-1/2 antibody and follow-up of serointederminate donors are essential to ensure blood safety especially in areas where we have found HTLV infected donors.
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http://dx.doi.org/10.1186/s12977-020-00546-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791705PMC
January 2021

Identification of structural properties influencing the metabolism of polycyclic aromatic hydrocarbons by cytochrome P450 1A1.

Sci Total Environ 2021 Mar 8;758:143997. Epub 2020 Dec 8.

Key Lab of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, PR China; State Key Lab of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, PR China. Electronic address:

Cytochrome P450 1A1 (CYP1A1) has served as a known metabolic enzyme that mediates the carcinogenesis of polycyclic aromatic hydrocarbons (PAHs). However, the structural mechanism involved in the metabolic capacity remains unclear. In this study, thirty-three calculated properties representing the physicochemical and electronic properties of PAH and PAH-CYP1A1 interactions were utilized to identify the key structural properties that affect metabolic processes, including binding ability, metabolic clearance, and mutagenicity, using a quantitative structure-activity relationship (QSAR) strategy combined with docking methods, QM/MM calculations and ab initio calculations. van der Waals interactions (glide vdw) appeared to be important for PAH binding to CYP1A1 and were mainly affected by the molecular weight and hydrophobic structures of PAHs. Interaction features between PAHs and heme, including the distance between iron and carbons of PAHs (Fe_C) and heme vdw, coordinately influence the metabolic clearance of PAHs. Furthermore, the electronic properties (ESP neg variance) appeared to be critical for the mutagenicity of PAHs by CYP1A1 through influencing epoxide metabolite formation. The QSAR models with these key properties provide a new perspective on the structural mechanism of PAH metabolism and provide a useful in silico tool for screening, classifying and predicting PAHs for their metabolism-related toxicities and risk assessment in the environment.
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http://dx.doi.org/10.1016/j.scitotenv.2020.143997DOI Listing
March 2021

Comparative Mitochondrial Analysis of Cnaphalocrocis exigua (Lepidoptera: Crambidae) and Its Close Relative C. medinalis.

J Insect Sci 2020 Nov;20(6)

Key Laboratory of Entomology and Pest Control Engineering, College of Plant Protection, Southwest University, Chongqing, China.

Rice leaffolders are important pests on rice in Asia, Oceania, and Africa, causing serious loss to rice production. There are two main rice leaffolders in China, namely Cnaphalocrocis medinalis (Guenée) and C. exigua (Butler) with the former having the ability of long-distance migration. To reveal the differences in the mitochondrial genomes (mitogenome) between them, we compared the completed mitogenome of C. exigua with three C. medinalis individuals. Although phylogenetic analysis based on the mitogenomic data strongly supported the close relationship between these two species, many differences were still being revealed. The results showed that the mitogenome of C. exigua was shorter in length (15,262 bp) and slight lower in AT content than that of C. medinalis. Except for the different start codons of nad3 and nad6 gene, we also found the cox1 gene had a typical start codon 'ATG' which suggested that the starting position of this gene must be reconsidered in the entire superfamily Pyraloidea. All tRNAs have a typical clover-leaf structure, except for the dihydrouridine (DHU) stem losing of trnS1, which has the atypical anticondon 'TCT' instead of 'GCT' in C. medinalis and most Pyraloidea species. Two intergenic regions (between trnY and cox1, nad3 and trnA) featured by AT repeats were only found in C. medinalis and even rarely appeared in reported Pyraloidea species. Furthermore, regardless of interspecific comparison or intraspecific comparison of these two species, protein coding genes, especially the atp8 genes, had quite different evolutionary rates.
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http://dx.doi.org/10.1093/jisesa/ieaa112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660152PMC
November 2020

Seroprevalence of Neutralizing Antibodies against Six Human Adenovirus Types Indicates the Low Level of Herd Immunity in Young Children from Guangzhou, China.

Virol Sin 2021 Jun 9;36(3):373-381. Epub 2020 Nov 9.

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, 510182, China.

Human adenoviruses (HAdVs) commonly cause many diseases such as respiratory diseases, gastroenteritis, cystitis worldwide. HAdV-3, -7, -4 and emergent HAdV-55 and HAdV-14 are the most important types causing severe respiratory diseases. There is no effective drug available for clinical treatment, and no vaccine available for the general population. Therefore, it is important to investigate the seroprevalence against HAdV for developing novel vaccines and vectors. In this study, we investigated the seroprevalence and titer levels of neutralizing antibodies (NAb) against HAdV-3, -4, -7, -14, -55, and -11 in total 278 healthy populations between 0 months and 49 years of age (228 children and 50 adults) from Guangzhou. In children under the age of 18 years, the seropositive rates were significantly increased against HAdV-3 at 12.07%, 33.96%, and 64.29% and against HAdV-7 at 0%, 18.87%, and 19.05% in age groups of 1-2, 3-5, and 6-17 years, respectively. The seroprevalence was very low (0% ~ 8.1%) for all other four types. In adults aged between 18 and 49 years, HAdV-3, -4, and -7 (> 50.00%) were the most common types, followed by HAdV-14 (38.00%), -55 (34.00%), and -11 (24.00%). Adults tended to have high NAb titers against HAdV-4 and -55. HAdV-55-seropositive donors tended to be HAdV-11- and HAdV-14-seropositive. These results indicated the low level of herd immunity against all six HAdV types in young children, and HAdV-14, -55, -11 in adults from Guangzhou City. Our findings demonstrate the importance of monitoring HAdV types and developing vaccines against HAdV for children and adults.
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http://dx.doi.org/10.1007/s12250-020-00307-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649710PMC
June 2021

Extracellular ubiquitin promotes hepatoma metastasis by mediating M2 macrophage polarization via the activation of the CXCR4/ERK signaling pathway.

Ann Transl Med 2020 Aug;8(15):929

Department of Transfusion Medicine, Huashan Hospital, Fudan University, Shanghai, China.

Background: Stored red blood cell (RBC) transfusion has been shown to enhance the risk of cancer recurrence. However, the underlying mechanism remains unknown. At our lab, we have demonstrated that the extracellular ubiquitin (eUb) released by aged RBCs could promote tumor metastasis in a melanoma mouse model. This study aimed to confirm the pro-tumor effect of eUb on hepatocellular carcinoma (HCC) and explore the related immunoregulatory mechanisms.

Methods: Forty HCC tissue specimens and the corresponding adjacent nontumor and normal liver tissues were collected. Two human hepatoma cell lines (MHCC-97H and HepG2.2.15), one murine hepatoma cell line (Hepa1-6), and one human monocyte cell line (THP-1) were adopted in this study. The coculture of hepatoma cells with macrophages was initiated with Transwell inserts. Cell migration was detected by Transwell and wound-healing assays, while tumor metastasis was measured by luciferase assay and H&E staining. Macrophage polarization was measured by flow cytometry, immunofluorescence, ELISA, qPCR, and Western blot. Protein expression was detected by Western blot, and immunoprecipitation was used to confirm the interaction between Ub and CXCR4 (CXC chemokine receptor type 4).

Results: Ub and CXCR4 were significantly upregulated in HCC tissues, and a positive correlation existed between them. , the migration of hepatoma cells was not affected by eUb directly, but their metastatic abilities were enhanced after coculture with the macrophages pretreated with eUb. Meanwhile, eUb promoted hepatoma cell metastasis in the lung and increased the ratio of M2 macrophages in the lung tissues and peripheral blood of tumor-bearing mice. Furthermore, the eUb-induced M2 macrophage polarization was related to the activation of the CXCR4/ERK (extracellular regulated protein kinase) signaling pathway.

Conclusions: Extracellular ubiquitin promoted hepatoma metastasis through M2 macrophage polarization via the activation of the CXCR4/ERK signaling pathway, indicating that a personalized transfusion strategy is needed for the treatment of HCC patients. Neutralizing Ub in stored RBC units could lessen the detrimental clinical outcomes induced by the transfusion of stored RBCs.
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http://dx.doi.org/10.21037/atm-20-1054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7475394PMC
August 2020

Low prevalence of antibodies against SARS-CoV-2 among voluntary blood donors in Guangzhou, China.

J Med Virol 2021 03 30;93(3):1743-1747. Epub 2020 Sep 30.

Institute of Blood Transfusion, Guangzhou Blood Center, Guangzhou, Guangdong, China.

Since the first case of COVID-19 reported in late December of 2019 in Wuhan, China, the SARS-CoV-2 virus has caused approximately 20 million infections and 732 thousand deaths around the world by 11 August 2020. Although the pathogen generally infects the respiratory system, whether it is present in the bloodstream and whether it poses a threat to the blood supply during the period of the outbreak is of serious public concern. In this study, we used enzyme-linked immunosorbent assay (ELISA) to screen total antibodies against SARS-CoV-2 in 2199 blood donors, who had donated blood at the Guangzhou Blood Center during the epidemic. The Ig-reactive samples were further characterized for IgA, IgG, and IgM subtypes by ELISA and viral nucleic acid by real-time polymerase chain reaction. Among the 2199 plasma samples, seven were reactive under total antibodies' screening. Further testing revealed that none of them had detectable viral nucleic acid or IgM antibody, but two samples contained IgA and IgG. The IgG antibody titers of both positive samples were 1:16 and 1:4, respectively. Our results indicated a low prevalence of past SARS-CoV-2 infection in our blood donors, as none of the tests were positive for viral nucleic acid and only 2 out of 2199 (0.09%) of samples were positive for IgG and IgA. There would be a limited necessity for the implementation of such testing in blood screening in a COVID-19 low-risk area.
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http://dx.doi.org/10.1002/jmv.26445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461367PMC
March 2021

Successful Reversal of Opioid-Induced Hyperalgesia and Allodynia with Duloxetine.

Pain Med 2021 04;22(4):1010-1012

Department of Internal Medicine (VIP Ward), Cancer Hospital of China Medical University, Shenyang, Liaoning Province, P R China.

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http://dx.doi.org/10.1093/pm/pnaa184DOI Listing
April 2021

Early experience with convalescent plasma as immunotherapy for COVID-19 in China: Knowns and unknowns.

Vox Sang 2020 Aug;115(6):507-514

Department of Transfusion Medicine, Huashan Hospital, Fudan University, Shanghai, China.

Background And Objectives: In the absence of a vaccine or specific drug treatment options for coronavirus disease (COVID-19), attention has been shifted in China to the possible therapeutic use of convalescent plasma. COVID-19 convalescent plasma (CCP) is currently under investigation. We summarized clinical studies and other research data available as of 5 May 2020 on CCP therapy according to the Clinical Treatment Guideline of COVID-19 Convalescent Plasma in China, as well as clinical experience at the First Affiliated Hospital of Zhejiang University, as part of a comprehensive anti-epidemic strategy.

Materials And Methods: As of 5 May 2020, when the epidemic was well-controlled in China, healthcare databases and sources of English literature relating to convalescent plasma were searched and reviewed. Sources of clinical and methodological heterogeneity were identified.

Results: As of 5 May 2020, up to 2000 samples of CCP had been collected across China and administered to 700 COVID-19 patients. From donors, 200-400 ml of plasma was collected at each donation, with antibody titres > 1:160. We identified three clinical studies for COVID-19 in China. Analyses showed a statistically significant improvement in clinical outcomes compared with untreated cases (P < 0.001). No adverse effects were reported.

Conclusion: From initial studies, convalescent plasma therapy appears effective and safe for COVID-19. However, there is clearly a need for well-designed RCTs (randomized controlled trials) or other formal studies to further evaluate the efficacy and any potential adverse effects of CCP.
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http://dx.doi.org/10.1111/vox.12968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300975PMC
August 2020

Novel hepatitis B virus surface antigen mutations associated with occult genotype B hepatitis B virus infection affect HBsAg detection.

J Viral Hepat 2020 09 11;27(9):915-921. Epub 2020 May 11.

Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China.

The causative factors of occult hepatitis B infection are complicated and not yet been fully elucidated. Mutations in hepatitis B virus (HBV) S gene are one of the factors may contributing to occult infection. In this study, 89 blood donors with genotype B occult HBV infection were investigated. Fifty-seven hepatitis B surface antigen (HBsAg)-positive/HBV DNA-positive blood donors served as control group for comparison. Occult HBV-related mutations with a high incidence (P < .05) in the S gene were identified. To further verify these occult infection-related mutations, a conservative full-gene expression vector of HBV B genotype (pHBV1.3B) was constructed. Then, the mutant plasmids on the basis of pHBV1.3B were constructed and transfected into HepG2 cells. Extracellular as well as intracellular HBsAg was analysed by electrochemical luminescence and cellular immunohistochemistry. Ten occult infection-related mutations (E2G, Q101R, K122R, M133T, D144E, G145R, V168A, S174N, L175S and I226S) were significantly more frequent in the occult infection group (P < .05). Five of the ten mutations (E2G, D144E, G145R, V168A and S174N) strongly decreased extracellular HBsAg level (P < .05) in the transfection system. Notably, the E2G mutation had the most significant impact on the ratio of extracellular HBsAg (3.8% vs pHBV1.3B) and intracellular HBsAg (239.3% vs pHBV1.3B) (P < .05), and the fluorescence density of E2G mutant HBsAg was significantly higher than that of pHBV1.3B (P < .0001). Hence, ten mutations were associated with genotype B occult HBV infection; E2G and V168A were novel mutations which we confirmed significantly affect HBsAg detection. E2G might cause HBsAg secretion impairment that results in intracellular accumulation and a decrease in HBsAg secretion.
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http://dx.doi.org/10.1111/jvh.13309DOI Listing
September 2020
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