Publications by authors named "Jie Sun"

1,506 Publications

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Combination prostate cancer therapy: Prostate-specific membranes antigen targeted, pH-sensitive nanoparticles loaded with doxorubicin and tanshinone.

Drug Deliv 2021 Dec;28(1):1132-1140

Department of Pharmacy, Municipal Hospital of Zaozhuang, Zaozhuang, P. R. China.

Prostate cancer is the second most frequently diagnosed cancer in the men population. Combination anticancer therapy using doxorubicin (DOX) and another extract of traditional Chinese medicine is one nano-sized drug delivery system promising to generate synergistic anticancer effects, maximize the treatment effect, and overcome multi-drug resistance. The purpose of this study is to construct a drug delivery system for the co-delivery of DOX and tanshinones (TAN). Lipid nanoparticles loaded with DOX and TAN (N-DOX/TAN) were prepared by emulsification and solvent-diffusion method. PSMA targeted nanoparticles loaded with DOX and TAN (P-N-DOX/TAN) were synthesized by conjugating a PSMA targeted ligand to N-DOX/TAN. We evaluate the performance of this system and . P-N-DOX/TAN has a size of 139.7 ± 4.1 nm and a zeta potential of 11.2 ± 1.6 mV. The drug release of DOX and TAN from P-N-DOX/TAN was much faster than that of N-DOX/TAN. N-DOX/TAN presented more inhibition effect on tumor growth than N-DOX and N-TAN, which is consistent with the synergistic results and successfully highlighting the advantages of combing the DOX and TAN in one system. P-N-DOX/TAN achieved higher uptake by LNCaP cells (58.9 ± 1.9%), highest tumor tissue distribution, and the most significant tumor inhibition efficiency. The novel nanomedicine offers great promise for the dual drug delivery to prostate cancer cells, showing the potential of synergistic combination therapy for prostate cancer.
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http://dx.doi.org/10.1080/10717544.2021.1931559DOI Listing
December 2021

Comparison of the Efficacy of S-1 Plus Oxaliplatin or Capecitabine Plus Oxaliplatin for Six and Eight Chemotherapy Cycles as Adjuvant Chemotherapy in Patients With Stage II-III Gastric Cancer After D2 Resection.

Front Oncol 2021 24;11:684627. Epub 2021 May 24.

Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China.

Objective: To compare the efficacy of adjuvant chemotherapy with six or eight cycles of S-1 plus oxaliplatin (SOX) or Capecitabine plus oxaliplatin (XELOX) after D2 resection of GC.

Design And Participants: We collected 470 cases of patients with TNM stage II and III GC who underwent D2 gastrectomy in the Harbin Medical University Cancer Hospital from January 2007 to December 2017 and received six or eight cycles of SOX or XELOX regimen. This study was designed to evaluate the prognosis of patients receiving six or eight cycles of SOX or XELOX chemotherapy and identify the appropriate number of chemotherapy cycles.

Results: Among the 470 study participants [340 (72.3%) males; median age, 50 years (range, 24-76 years)], 355 and 115 received XELOX or SOX regimen chemotherapy, respectively. The number of 152 patients included in this study who received 6 and 8 cycles of chemotherapy in stage II and stage III without considering chemotherapy regimens were 125 and 27. The median DFS was, respectively, 14.9 months and 26.8 months (P = 0.08), the median OS was, respectively, 30.2 months and 30.8 months (P = 0.5), the difference was not statistically significant. Comprehensive survival analysis of XELOX and SOX group showed no significant difference for DFS (P = 0.29) and OS (P = 0.61). The total number of stage III GC patients who received six and eight cycles of chemotherapy was 92 and 19, respectively. The median DFS of patients who received six and eight cycles of chemotherapy was 14.6 and 23.2 months (P = 0.3), respectively. The median OS of patients who received six and eight cycles of chemotherapy was 26 and 30.6 months (P = 0.9), respectively. Comprehensive analysis of DFS (P=0.73) and OS (P=0.6) shows no difference between the XELOX group SOX groups. Subgroup analysis revealed significant differences in the gender (P = 0.05) and histological classification (P < 0.05) distribution.

Conclusion: Regardless of the XELOX regimen or the SOX regimen, similar survival benefits are observed in patients receiving six or eight chemotherapy cycles irrespective of the regimen used. The XELOX and SOX regimens are well tolerated in patients undergoing D2 resection of GC.
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http://dx.doi.org/10.3389/fonc.2021.684627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8181140PMC
May 2021

Screening and Prognostic Value of Methylated Septin9 and its Association With Clinicopathological and Molecular Characteristics in Colorectal Cancer.

Front Mol Biosci 2021 20;8:568818. Epub 2021 May 20.

Department of Pathology, Tianjin Union Medical Center, Tianjin, China.

Screening of CRC continues to show poor compliance of endoscopy examination. The detection of mSEPT9 in peripheral blood is among the safe and simple early screening methods for CRC. The issue of how to elucidate whether detection of mSEPT9 in peripheral blood can effectively improve compliance of endoscopy and increase the early diagnosis rate of CRC and the relationship between levels of mSEPT9 in the peripheral blood and clinical stage, pathological classification, and expression of characteristic molecules in CRC remains unsolved. A total of 7759 individuals participated in the study that was performed using a questionnaire for screening of high-risk CRC. The endoscopic detection compliance of individuals with high-risk CRC who underwent the fecal occult blood test (FOBT) or mSEPT9 test was compared based on the results of the questionnaire. Additionally, correlation of mSEPT9 levels in the peripheral blood with clinicopathological features, mutation status of , mismatch repair deficiency (dMMR), and /// genotype was analyzed, and association of biomarkers with cancer-specific survival (CSS) and time to recurrence (TTR) was compared. We also detected levels of mSEPT9 in the peripheral blood of patients with CRC 7 days after surgery and compared the prognostic value of mSEPT9 with CEA. Results of our study showed that the mSEPT9 test could improve compliance of endoscopy and indicated a higher percentage of patients with positive mSEPT9 willing to undergo endoscopy detection than in those with positive FOBT. The specificity and sensitivity of mSEPT9 were better than that of FOBT for the detection of CRC. mSEPT9 was associated with the TNM stage, dMMR, and mutations in , and . A Ct value of mSEPT9 ≤ 37.5 was significantly related to poor CSS. mSEPT9 could affect association of dMMR and and mutations with CSS in a specific stage of CRC. The positive rate of mSEPT9 after surgery was found to correlate with poor TTR, and sensitivity was higher than CEA. The combination of mSEPT9 with CEA had a better prognostic value than that of mSEPT9 alone. The level of mSEPT9 was related to dMMR, mutations in , , and , and was an effective biomarker for the prognosis of patients with CRC.
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http://dx.doi.org/10.3389/fmolb.2021.568818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173126PMC
May 2021

Predictive Value of Cerebrospinal Fluid Biomarkers for Tap Test Responsiveness in Patients With Suspected Idiopathic Normal Pressure Hydrocephalus.

Front Aging Neurosci 2021 20;13:665878. Epub 2021 May 20.

Department of Neurology, Aviation General Hospital, Beijing, China.

The value of cerebrospinal fluid (CSF) biomarkers for assessing idiopathic normal pressure hydrocephalus (iNPH) must be determined. This prospective study aimed to reveal the correlation between CSF biomarkers and clinical symptoms of iNPH and the predictive value of these biomarkers for tap test responsiveness. Thirty-nine patients with suspected iNPH were recruited, contributed qualified CSF, and underwent a tap test and unified pre- and post-test evaluations of the neurological function. The analysis of biomarkers from the patients' CSF showed decreased levels of tau and its phosphorylated form, especially in the tap test (+) group. The responsiveness of the tap test was also related to the number of combined symptoms ( < 0.01), and a correlation was found between the end pressure or pressure difference in CSF and tap test responsiveness ( < 0.05). The results of the binary logistic regression analysis showed that (tap test responsiveness) = 1/1 + e - (-5.505 + 55.314 * ratio of p/-tau - 1.586 * numbers of combined symptoms). The combined indicators (-5.505 + 0.553 * percentage of p/-tau - 1.586 * numbers of combined symptoms) resulted in the highest sensitivity and specificity of 94.12% and 72.73%, respectively. CSF biomarkers may be assessed to judge tap test responsiveness, which is beneficial for the feasibility of a clinical application.
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http://dx.doi.org/10.3389/fnagi.2021.665878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172576PMC
May 2021

Frailty as a predictor of increased one-year mortality after elective non-cardiac surgery: A prospective cohort study.

J Clin Anesth 2021 Oct 1;73:110371. Epub 2021 Jun 1.

Department of Anesthesiology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China. Electronic address:

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http://dx.doi.org/10.1016/j.jclinane.2021.110371DOI Listing
October 2021

Myocardial fibrosis combined with NT-proBNP improves the accuracy of survival prediction in ADHF patients.

BMC Cardiovasc Disord 2021 May 28;21(1):264. Epub 2021 May 28.

Department of Cardiology, Zhongshan People Hospital, Sun Yat-Sen University, No. 2 Sunwen East Road, Zhongshan, 528400, Guangdong, People's Republic of China.

Background: Soluble suppression of tumorigenesis-2 (sST2), Procollagen Type III N-Terminal Peptid (PIIINP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) have been verified their role in predicting survival in acutely decompensated heart failure (ADHF). However, whether their combination could improve more specific and sensitive prognostic information than NT-proBNP alone remains unclear.

Methods: This was a prospective study, in which 217 ADHF patients at admission were enrolled from November 2018 and August 2019 (mean age 66.18 years ± 13.60, 63.98% male). The blood samples were collected to measure the concentrations of NT-proBNP, sST2 and PIIINP in the first 24 h of hospitalizations. All-cause mortality was registered for all patients after they were discharge over a median period of 339 days.

Results: In univariate Cox analysis, the three biomarkers were predictive of short-term mortality of ADHF patients. After adjusted for some clinical variables including age, admission systolic blood pressure, peripheral edema on admission, history of chronic obstructive pulmonary disease, admission sodium < 135 mmol/L, admission hemoglobin, NT-proBNP, sST2 and PIIINP was significantly associated with the poor outcome (hazard ratio [HR] 1.32, 95% confidence interval [CI] 1.14-1.53, P < 0.01; HR 1.21, 95% CI 1.03-1.43, P = 0.020; HR 1.40, 95% CI 1.08-1.81, P = 0.011). After added with Log2 PIIINP, but not Log2 sST2, the area under the curves (AUC) in the model of clinical variables and Log2 NT-proBNP could increase from 0.79 to 0.85 (95% CI 0.0071-0.10, P = 0.024). Furthermore, compared with the model of clinical variables, Log2 NT-proBNP, the improvement in the prognostic model of clinical variables, Log2 NT-proBNP and Log2 PIIINP had statistical significance [net reclassification improvement (NRI) 0.31, P = 0.018; integrated discrimination improvement (IDI) 0.068, P < 0.01].

Conclusions: NT-proBNP, sST2 and PIIINP are independent prognostic factors for all-cause mortality in ADHF patients. Furthermore, the combination of NT-proBNP and PIIINP may provide incremental prognostic value over NT-proBNP in the survival of ADHF patients.
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http://dx.doi.org/10.1186/s12872-021-02083-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164226PMC
May 2021

Regression in carotid plaque lipid content and neovasculature with PCSK9 inhibition: A time course study.

Atherosclerosis 2021 Jun 19;327:31-38. Epub 2021 May 19.

University of Washington, Seattle, WA, USA.

Background And Aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors reduce cardiovascular events, but their effects on atherosclerotic plaque remain elusive. Using serial magnetic resonance imaging (MRI), we studied changes in carotid plaque lipid content and neovasculature under PCSK9 inhibition with alirocumab.

Methods: Among patients with low-density lipoprotein cholesterol (LDL-C) ≥70 mg/dl but ineligible for high-dose statin therapy, those with lipid core on carotid MRI were identified to receive alirocumab 150 mg every 2 weeks. Follow-up MRI was performed at 3, 6, and 12 months after treatment. Pre- and post-contrast MRI were acquired to measure percent lipid core volume (% lipid core). Dynamic contrast-enhanced MRI was acquired to measure the extravasation rate of gadolinium contrast (K), a marker of plaque neovasculature.

Results: Of 31 patients enrolled, 27 completed the study (mean age: 69 ± 9; male: 67%). From 9.8% at baseline, % lipid core was progressively reduced to 8.4% at 3 months, 7.5% at 6 months, and 7.2% at 12 months (p = 0.014 for trend), which was accompanied by a progressive increase in % fibrous tissue (p = 0.009) but not % calcification (p = 0.35). K was not reduced until 12 months (from 0.069 ± 0.019 min to 0.058 ± 0.020 min; p = 0.029). Lumen and wall areas did not change significantly during the study period.

Conclusions: Regression in plaque composition and neovasculature were observed under PCSK9 inhibition on carotid MRI, which provides unique insight into the biological process of plaque stabilization with disease-modifying therapies.
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http://dx.doi.org/10.1016/j.atherosclerosis.2021.05.008DOI Listing
June 2021

A novel prognostic model for angioimmunoblastic T-cell lymphoma: A retrospective study of 55 cases.

J Int Med Res 2021 May;49(5):3000605211013274

Department of Haematology/Oncology and Paediatric Oncology, Guangxi Medical University Affiliated Cancer Hospital, Nanning, Guangxi, China.

Objective: To explore prognostic factors and develop an accurate prognostic prediction model for angioimmunoblastic T-cell lymphoma (AITL).

Methods: Clinical data from Chinese patients with newly diagnosed AITL were retrospectively analysed. Overall survival (OS) and progression-free survival (PFS) were estimated using Kaplan-Meier method survival curves; prognostic factors were determined using a Cox proportional hazards model. The sensitivity and specificity of the predicted survival rates were compared using area under the curve (AUC) of receiver operating characteristic (ROC) curves.

Results: The estimated 5-year OS and PFS of 55 eligible patients with AITL were 22% and 3%, respectively. Multivariate analysis showed that the presence of pneumonia, and serous cavity effusions at initial diagnosis were significant prognostic factors for OS. Based on AUC ROC values, our novel prognostic model was superior to IPI and PIT based models and suggested better diagnostic accuracy.

Conclusions: Our prognostic model based on pneumonia, and serous cavity effusions at initial diagnosis enabled a balanced classification of AITL patients into different risk groups.
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http://dx.doi.org/10.1177/03000605211013274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161901PMC
May 2021

The roles and prognostic significance of ABI1-TSV-11 expression in patients with left-sided colorectal cancer.

Sci Rep 2021 May 24;11(1):10734. Epub 2021 May 24.

Department of Central Laboratory and Institute of Clinical Molecular Biology, Peking University People's Hospital, Beijing, China.

Abnormally expressed and/or phosphorylated Abelson interactor 1 (ABI1) participates in the metastasis and progression of colorectal cancer (CRC). ABI1 presents as at least 12 transcript variants (TSVs) by mRNA alternative splicing, but it is unknown which of them is involved in CRC metastasis and prognosis. Here, we firstly identified ABI1-TSV-11 as a key TSV affecting the metastasis and prognosis of left-sided colorectal cancer (LsCC) and its elevated expression is related to lymph node metastasis and shorter overall survival (OS) in LsCC by analyzing data from The Cancer Genome Atlas and TSVdb. Secondly, ABI1-TSV-11 overexpression promoted LoVo and SW480 cells adhesion and migration in vitro, and accelerated LoVo and SW480 cells lung metastasis in vivo. Finally, mechanism investigations revealed that ABI1-isoform-11 interacted with epidermal growth factor receptor pathway substrate 8 (ESP8) and regulated actin dynamics to affect LoVo and SW480 cells biological behaviors. Taken together, our data demonstrated that ABI1-TSV-11 plays an oncogenic role in LsCC, it is an independent risk factor of prognosis and may be a potential molecular marker and therapeutic target in LsCC.
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http://dx.doi.org/10.1038/s41598-021-90220-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144562PMC
May 2021

An experimental and theoretical study on the growth of plate-like β-HMX crystals in the hydroxylated interlayer space.

Phys Chem Chem Phys 2021 Jun;23(21):12340-12349

State Key Laboratory of Chemical Resource Engineering, Institute of Computational Chemistry, College of Chemistry, Beijing University of Chemical Technology, Beijing 100029, P. R. China.

Plate-like β-HMX crystals are grown in the hydroxylated interlayer space using a crystallization technique combining the cooling crystallization and solvent-antisolvent methods. The obtained crystals have been investigated by X-ray diffraction (XRD), scanning electron microscopy (SEM), and atomic force microscopy (AFM). The experimental results indicate that the most morphologically important face of the plate-like β-HMX crystals is the (011) face adopting a layer-by-layer growth mode. Meanwhile, molecular dynamics (MD) simulations were performed to study the crystal morphology in HMX crystal growth in the hydroxylated interlayer space based on a modified attachment energy (MAE) model. The calculated results show that the major face is the (011) face and the interaction energies between the crystal face and the hydroxylated interlayer are in the order of (011) > (110) > (020), which agree well with the experimental results above.
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http://dx.doi.org/10.1039/d1cp00959aDOI Listing
June 2021

Demethylation of the SFRP4 Promoter Drives Gastric Cancer Progression via the Wnt pathway.

Mol Cancer Res 2021 May 20. Epub 2021 May 20.

Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.

Wnt signaling is believed to be an important contributor to tumor development and has been reported to be modulated by secreted frizzled-related proteins (SFRP). Nevertheless, the role of secreted frizzled-related protein 4 (SFRP4) in tumorigenesis remains controversial. We aim to explore its biological function in gastric cancer. Genomes analysis based on the Gene Expression Omnibus (GEO) dataset was used to find the differential gene expression between different tumor-node-metastasis (TNM) stages of gastric cancer. IHC was used to determine the relationship between SFRP4 expression and clinicopathologic characteristics in patients with gastric cancer. The influence of SFRP4 on tumor progression was evaluated by CCK-8, colony formation, cell apoptosis, and cell cycle , as well as xenograft model . The methylation status of SFRPs was examined in gastric cancer specimens by quantitative methylation analysis. SFRP4 was most upregulated in advanced gastric cancer. High intratumoral SFRP4 expression, which was associated with tumor invasion and metastasis, was also a poor prognostic indicator for patients with gastric cancer. and studies revealed that SFRP4 could promote tumor growth; however, IWR-1 could suppress tumor growth mediated by SFRP4 overexpression. Mechanistic exploration found that SFRP4 was overexpressed by the decrease of promoter methylation and thus could competitively antagonize the inhibitory effect of SFRP1 on Wnt pathway activation and tumor progression in gastric cancer. IMPLICATIONS: In gastric cancer, the expression of SFRP4 was upregulated by decreased methylation. High intratumoral SFRP4 expression could activate the Wnt pathway to promote tumor progression and predict poor survival of patients with gastric cancer.
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http://dx.doi.org/10.1158/1541-7786.MCR-20-0933DOI Listing
May 2021

Identification of gene signatures and potential therapeutic targets for acquired chemotherapy resistance in gastric cancer patients.

J Gastrointest Oncol 2021 Apr;12(2):407-422

Department of Medical Oncology, Wuxi People's Hospital of Nanjing Medical University, Wuxi, China.

Background: Gastric cancer (GC) is the most common type of gastrointestinal cancer, and has been studied extensively. However, resistance to chemotherapeutic agents has become a major problem, leading to treatment failure. This study aimed to investigate the molecular mechanisms mediating acquired resistance to cisplatin and fluorouracil (CF) combination-based chemotherapy in GC patients.

Methods: The microarray datasets (GSE14209, GSE30070) were downloaded from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) using the limma package in R/Bioconductor. Possible targets of the DEMs were predicted using miRWalk, and the putative miRNA-mRNA regulatory network was constructed using Cytoscape software. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) analyses were then conducted and visualized using the Search Tool for Retrieval of Interacting Genes (STRING) and Cytoscape. The prognostic value of hub genes was revealed by Kaplan-Meier Plotter. The causal relationships and interactions between proteins were displayed using DisNor. Finally, similarity analysis was conducted using the Connectivity Map (CMap) profiles to predict a group of small molecules in GC treatment.

Results: A total of 394 DEGs and 31 DEMs were identified after analysis of pre- and post-treatment samples of clinical responders to CF therapy. TM9SF4, hsa-miR-185-5p, and hsa-miR-145-5p were found to be critical in the miRNA-mRNA regulatory network. The DEGs were found to be mainly enriched in the processes of ribonucleoprotein complex assembly, catalytic activity acting on RNA, mitochondrial matrix, and thermogenesis. The DEMs were predominantly found to be involved in single-stranded RNA binding and endoplasmic reticulum lumen. HDAC5, DDX17, ILF3, and SDHC were identified as hub genes in the PPI network. Of these, HDAC5, DDX17, and ILF3 were found to be closely related to the overall survival of GC patients. DisNor identified the first neighbors of the key genes. Furthermore, CMap profiles predicted a group of small molecules, including several histone deacetylase inhibitors (HDACIs), menadione, and mibefradil, which could serve as promising therapeutic agents to reverse acquired resistance to CF therapy.

Conclusions: Our findings reveal new targets and alternative therapies to overcome the acquired resistance of GC patients to CF treatment.
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http://dx.doi.org/10.21037/jgo-21-81DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107589PMC
April 2021

Time-Series Analysis of Continuous Glucose Monitoring Data to Predict Treatment Efficacy in Patients with T2DM.

J Clin Endocrinol Metab 2021 May 19. Epub 2021 May 19.

Medical Research Center, Ningbo City First Hospital, Ningbo, Zhejiang Province, China.

Context: There is a challenge to predict treatment effects in patients with T2DM.

Objective: To assess and predict treatment effects in patients with T2DM through time-series analysis of continuous glucose monitoring (CGM) measurements.

Design: We extracted and clustered the trend components of CGM measurements to generate representative time-series profiles, which were used as a predictor of treatment effects in groups of patients.

Setting And Participants: We recruited 111 outpatients with T2DM at Ningbo City First Hospital.

Intervention: The patients underwent CGM measurement for 14 days at the beginning of glucose-lowering treatment.

Main Outcome Measures: HbA1c and FPG were obtained at the beginning and 6-month of treatment.

Results: 111 patients each had 960 -1344 CGM measurements for 14 days at 96 measurements per day. The patients were classified into three groups according to the profiles of trend components of CGM observed values by time-series clustering method, including decreasing (47 patients), increasing (26 patients), and unchanged (38 patients) profiles. After six-month glucose-lowering treatment, FPG declined from 10.2 to 6.8 mmol/L (a decline of 3.5 mmol/L) in the decreasing group, from 8.9 to 9.2 mmol/L (a rise of 0.3 mmol/L) in the increasing group, and from 8.4 to 7.5 mmol/L (a decline of 0.9 mmol/L). The changes of HbA1c were 2.2%, 0.2%, and 0.9% for the three groups (P<0.01), respectively.

Conclusions: Clustering of the trend components of CGM data generates representative CGM profiles that are predictive of six-month therapeutic effects for T2DM.
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http://dx.doi.org/10.1210/clinem/dgab356DOI Listing
May 2021

A novel tumor suppressor ASMTL-AS1 regulates the miR-1228-3p/SOX17/β-catenin axis in triple-negative breast cancer.

Diagn Pathol 2021 May 18;16(1):45. Epub 2021 May 18.

Department of Breast Surgery, Dushuhu Public Hospital Affiliated to Soochow University, 215006, SuZhou, JiangSu, China.

Background: Triple-negative breast cancer (TNBC) is a special type of breast cancer that lacks effective therapeutic targets. There is a significant need to clarify its pathogenesis, so as to bring new targeted approaches for TNBC management. Here, we identified a long-non coding RNA (lncRNA) ASMTL-AS1 that linked to TNBC development and progression.

Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot assays were used to test gene and protein levels, respectively. The regulatory axis of miR-1228-3p/SOX17/β-catenin was determined by luciferase reporter and RNA pull-down assays. In vivo assay was conducted by using the nude mice model via subcutaneous transplantation of tumor cells.

Results: ASMTL-AS1 was significantly downregulated in TNBC tissues compared to normal tissues, which was closely associated with aggressive clinical features and unfavorable prognosis. Lentivirus-mediated ASMTL-AS1 overexpression evidently reduced the ability of TNBC cell colony formation, activity and invasion by more than 2.5 times. RNA pull-down and luciferase reporter assays revealed that miR-1228-3p directly bound to ASMTL-AS1, ASMTL-AS1 increased SOX17 expression via sponging and repressing miR-1228-3p. Subsequently, the upregulated SOX17 trans-suppressed β-catenin expression, resulting in the inactivation of carcinogenic Wnt/β-catenin signaling, thereby restraining TNBC cell growth and dissemination. Importantly, the xenograft tumor model showed that the ASMTL-AS1 overexpression significantly retarded tumor growth, and negatively regulated Wnt/β-catenin pathway.

Conclusions: Our data characterize a novel tumor suppressor in TNBC, restoration of ASMTL-AS1 may be a candidate therapeutic intervention for TNBC patients.
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http://dx.doi.org/10.1186/s13000-021-01105-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130432PMC
May 2021

Atherosclerotic Burden and Remodeling Patterns of the Popliteal Artery as Detected in the Magnetic Resonance Imaging Osteoarthritis Initiative Data Set.

J Am Heart Assoc 2021 Jun 17;10(11):e018408. Epub 2021 May 17.

Department of Radiology University of Washington Seattle WA.

Background An artificial intelligence vessel segmentation tool, Fully Automated and Robust Analysis Technique for Popliteal Artery Evaluation (FRAPPE), was used to analyze a large databank of popliteal arteries imaged through the OAI (Osteoarthritis Initiative) to study the impact of atherosclerosis risk factors on vessel dimensions and characterize remodeling patterns. Methods and Results Magnetic resonance images from 4668 subjects contributing 9189 popliteal arteries were analyzed using FRAPPE. Age ranged from 45 to 79 years (median, 61), and 58% were women. Mean lumen diameter, mean outer wall diameter, and mean wall thickness (MWT) were measured per artery. Their median values were 5.8 mm (interquartile range, 5.2-6.5 mm), 7.3 mm (interquartile range, 6.7-8.1 mm), and 0.78 mm (interquartile range, 0.73-0.84 mm) respectively. MWT was associated with multiple cardiovascular risk factors, with age (4.2% increase in MWT per 10-year increase in age; 95% CI, 3.9%-4.5%) and sex (8.6% higher MWT in men than women; 95% CI, 7.7%-9.3%) being predominant. On average, lumen and outer wall diameters increased with increasing MWT until the thickness was 0.92 mm for men and 0.84 mm for women. After this point, lumen diameter decreased steadily, more rapidly in men than women (-7.9% versus -6.1% per 25% increase in MWT; <0.001), with little change in outer wall diameter. Conclusions FRAPPE has enabled the analysis of the large OAI knee magnetic resonance imaging data set, successfully showing that popliteal atherosclerosis is predominantly associated with age and sex. The average vessel remodeling pattern consisted of an early phase of compensatory enlargement, followed by a negative remodeling, which is more pronounced in men.
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http://dx.doi.org/10.1161/JAHA.120.018408DOI Listing
June 2021

Effects of decapitated and root-pruned Sedum alfredii on the characterization of dissolved organic matter and enzymatic activity in rhizosphere soil during Cd phytoremediation.

J Hazard Mater 2021 May 8;417:125977. Epub 2021 May 8.

College of Resources and Environment, Yangtze University, Wuhan, China. Electronic address:

Decapitation and root pruning, can impact plant morphological and physiological characteristics, which may determine the efficiency of phytoremediation. However, the effects of decapitated and root-pruned plants on the characterization of dissolved organic matter (DOM) and enzymatic activity, which determine the bioavailability of soil pollutants, have rarely been reported. This study aims to characterize DOM and enzymatic activity in the rhizosphere soil of Sedum alfredii when treated by decapitation and root pruning. Decapitation, slight pruning (10% root cutting), and their combination stimulated S. alfredii to secrete more DOM in the rhizosphere soil compared with the control. Furthermore, the proportions of hydrophilic increased from 42.7% in the control to 57.1% in the decapitation and slight pruning combination. Soil urease, invertase, and neutral phosphatase activities were higher in the rhizosphere soil of decapitated and root-pruned S. alfredii, and the highest values were observed with their combination. DOM from the soils of decapitated and root-pruned S. alfredii had significantly higher Cd extraction ability compared with that of the untreated species. Based on the findings of this study, we suggest that decapitation and root pruning can improve the phytoremediation efficiency of S. alfredii by increasing the bioavailability of Cd in its rhizosphere.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125977DOI Listing
May 2021

Edge/direct-lit hybrid mini-LED backlight with U-grooved light guiding plates for local dimming.

Opt Express 2021 Apr;29(8):12179-12194

Current mini-LED backlights improve high-dynamic-range liquid crystal displays (LCDs) by using tens of thousands of direct-lit sources for local dimming. However, relative thick profile and high power consumption are the inherent limitations while compared with edge-lit backlights. By synthesizing edge- and direct-lit advantages, we propose a novel hybrid mini-LED backlight equipped with a specially designed integrated light guiding plate (LGP) for large-area displays. This LGP is seamlessly spliced by multiple physically segmented sub-LGPs with a scattering dot array on the bottom and U-shaped grooves at the corners. Each sub-LGP is a single local dimming zone that can be independently controlled. Scattering dot distribution can be numerically calculated even from multiple edge-lit sources. High optical performance and satisfactory local dimming effect are verified and analyzed via both simulation and experiment. The experimental spatial illuminance uniformity and the light extraction efficiency reach 81% and 83% while the crosstalk can be well suppressed below 0.2% between adjacent local dimming zones. The significant advantages of our design towards state-of-the-art mini-LED backlights include the zero optical distance for an ultra-thin profile, low mini-LED amount for local dimming, high optical efficiency, and infinite extension of zone number, which is expected to have a broad application prospect in the near future.
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http://dx.doi.org/10.1364/OE.421346DOI Listing
April 2021

Characterization and evaluation of a novel silver nanoparticles-loaded polymethyl methacrylate denture base: In vitro and in vivo animal study.

Dent Mater J 2021 May 11. Epub 2021 May 11.

Department of Stomatology, the Third Medical Center, Chinese PLA General Hospital.

The aim of this study was to optimize the preparation method of polymethyl methacrylate (PMMA) denture base loaded with nano silver (NAg), to more effectively and safely impart sustainable antibacterial functions. NAg solution was synthetized and mixed with acrylic acid and methyl methyacrylate (MMA) monomer in order to prepare a new type of NAg solution (NS)/polymer methyl methacrylate denture base specimens (NS/PMMA). The surface morphology, mechanical strength, antimicrobial activity, anti-aging performance, cytotoxicity and biocompatibility of NS/PMMA denture base were evaluated in comparison with specimens fabricated using traditional NAg adding methods and NAg-free denture base. The aesthetic characteristics and mechanical strength of NS/PMMA denture base met the clinical application requirements. Meanwhile, NS/PMMA denture base showed better antibacterial activity, anti-aging properties, no cytotoxicity and displayed exceptional biocompatibility. NS/PMMA denture base thus has great potential for clinical application.
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http://dx.doi.org/10.4012/dmj.2020-129DOI Listing
May 2021

Protective effect of miR-138-5p inhibition modified human mesenchymal stem cell on ovalbumin-induced allergic rhinitis and asthma syndrome.

J Cell Mol Med 2021 Jun 11;25(11):5038-5049. Epub 2021 May 11.

Department of International Clinic, Qingdao Municipal Hospital, Qingdao, China.

The objective of the study is to evaluate the protective effects of human mesenchymal stem cells (hMSCs) modified with miR-138-5p inhibitor against the allergic rhinitis and asthma syndrome (ARAS). MiR-138-5p or negative control was transfected into hMSCs, and fluorescence-activated cell sorting was used to evaluate hMSC surface markers. Quantitative real-time PCR (qRT-PCR) was used to evaluate miR-138-5p, SIRT1, caspase-3, IL-6, IL-1β and TNF-α levels after TNF-α and IL-6 stimulations. hMSCs with or without miR-138-5p inhibition was intranasally administered into ARAS mice (n = 10 each group), followed by monitoring sneezing and nasal rubbing events to evaluate the allergic symptoms. Histamine, ovalbumin-specific IgE, IgG2a, IgG1 and LTC4 release were monitored in the serum and nasal lavage fluid using enzyme-linked immunosorbent assay. Expression of SIRT1 and HMGB1/TLR4 pathway in nasal mucosa was assessed. After miR-138-5p inhibitor transfection, the hMSC lineage was preserved. Binding between SIRT1 and miR-138-4p was observed, and miR-138-5p inhibition led to upregulation of SIRT1. Inhibition of miR-138-5p led to attenuated inflammatory responses of hMSCs upon TNF-α and IL-6 stimulation, and allergic symptoms in mice, as well as histamine and ovalbumin-specific IgG release. hMSCs with miR-138-5p inhibition showed characteristics of activated SIRT1 and inhibited HMGB1/TLR4 pathway. Inhibition of miR-138-5p in hMSCs enhanced its effects in attenuating inflammatory responses and allergic reaction in the ARAS model, which is presumably regulated by SIRT1 and the HMGB1/TLR4 pathway.
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http://dx.doi.org/10.1111/jcmm.16473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178307PMC
June 2021

A huge malignant phyllodes tumor of the breast with osteoclast-like giant cells: a case report.

Gland Surg 2021 Apr;10(4):1508-1514

Department of Breast Surgery, Second Affiliated Hospital of Dalian Medical University, Dalian, China.

The malignant phyllodes tumor (PT) of the breasts is a rare type of fibroepithelial neoplasm. Osteoclast-like giant cells (OLGCs) exist in many types of tumors. But malignant PTs with OLGCs were rarely reported. Here, we presented a case of a 49-year-old woman who had a 23 cm ×21 cm ×6 cm mass which was growing for 2 years in her left breast. The patient had moderate anemia due to the hemorrhage and exudation on the surface of the tumor. The imaging examinations such as PET-CT found no lymphatic involvement and distant metastasis. We performed mastectomy with a 2 cm surgical margin and free skin flap transplantation to restore the big wound. The vacuum assisted closure (VAC) system was used to promote wound healing. Histological examination of the surgical specimen showed atypical spindle-like stroma cells, marked nuclear pleomorphism, focal necrosis, and mitotic activity. Typical leaf-like architectures of PTs were observed in some regions. OLGCs were found in many sections of the tumor with a number of vascular proliferations. The final diagnosis was malignant PT with OLGCs. After a three-month follow-up, no local recurrence or metastasis was found. Autogenous skin grafts with VAC are available for large area skin defect after excising a huge breast tumor. The presence of OLGCs in malignant tumors may be related to necrosis and hemorrhage of the tumor. These findings also provide opportunities for understanding the mechanisms of tumor formation and development.
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http://dx.doi.org/10.21037/gs-20-845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102212PMC
April 2021

Physical Exercise is Associated with Glycemic Control among Women with Gestational Diabetes Mellitus: Findings from a Prospective Cohort in Shanghai, China.

Diabetes Metab Syndr Obes 2021 30;14:1949-1961. Epub 2021 Apr 30.

Clinical Research & Innovation Transformation Center, Shanghai Skin Diseases Hospital Affiliated to Tongji University, Shanghai, People's Republic of China.

Objective: Physical exercise during pregnancy is beneficial to women with gestational diabetes mellitus (GDM), but evidence on the association between physical exercise and glycemic control among women with GDM is limited in China. We conducted this study to understand the total exercise times, the percentage of abnormal plasma glucose (PG), and to explore if longer physical exercise is positively associated with a lower percentage of abnormal PG among GDM women.

Methods: During 2019 and 2020, we established a prospective cohort with 1,050 GDM women recruited. GDM was confirmed by a diagnostic 75g OGTT, and plasma glucose in over 10 hours overnight fasting and 2-hour after breakfast was implemented during a routine antenatal checkup. Information for demographic features and physical exercises among GDM women were collected by questionnaire interviews, and abnormal PG percentage was calculated as abnormal PG times divided by total PG test times.

Results: Among 1,050 GDM women, the percentage of exercise times <150 minutes/week, <30 minutes/day and <60 minutes/day was 17.33%, 26.57%, and 54.10%, respectively. The median percentage of abnormal PG was 40% (IQR=20-70%). GDM women with less exercise had a higher abnormal PG percentage (y=0.0049x-1.20x+88.96), ORs for women with exercise <150 minutes/week were 3.78 (95% CI=1.33-8.25), 6.97 (3.45-14.07), and 6.39 (3.61-11.33) compared with ≥ 150 minutes/week, and ORs for women with exercise <60 minutes/day were 4.62 (2.71-8.14), 3.58 (2.60-4.93), and 7.28 (4.31-12.30) compared with ≥60 minutes/day in groups divided by quartiles of P, P and P, respectively.

Conclusion: This study indicated high physical exercise times and abnormal PG percentage among women with GDM in Shanghai, China. GDM women with more exercise times had a lower percentage of abnormal PG, especially when exercise times were ≥60 minutes/day, and supplementary treatments should be provided for women with over 70% abnormal plasma glucose.
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http://dx.doi.org/10.2147/DMSO.S308287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096418PMC
April 2021

Ferric iron reduction reaction electro-Fenton with gas diffusion device: A novel strategy for improvement of comprehensive efficiency in electro-Fenton.

J Hazard Mater 2021 06 21;412:125195. Epub 2021 Jan 21.

Guangxi Key Laboratory of Clean Pulp & Papermaking and Pollution Control, Nanning 530004, PR China.

Applying the optimal 2-electron oxygen reduction reaction potential in electro-Fenton (2eORR-EF) for degradation has become a common strategy because of the highest HO generation rate in such condition. However, in 2eORR-EF system, the Fe(III) ions crystallize on the surface of cathode and form a layer of film according to SEM, XPS, XRD and Mössbauer spectrum resulting in poor reaction rate of EF. Hence, we propose FRR-EF, which is operated by applying the optimal potential of ferric iron reduction reaction (FRR) rather than that of 2eORR on cathode for EF. Gas diffusion device was also carried out to ensure the HO generation rate. In this novel strategy, only - 0.1 V was applied on cathode. High HO production rate (0.021 ± 0.002 mmol L min cm), and slow Fe(II) consumption rate (0.03 min) were achieved. The EIS result showed that at this potential, the formation of the Fe film was effectively alleviated, thus prolonging the degradation life of the cathode. This new strategy can balance both 2eORR and FRR, thus improving the comprehensive efficiency of EF, which provides essential references to the EF not only in potential operation but also in the design of reaction device.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125195DOI Listing
June 2021

Uncoupling of macrophage inflammation from self-renewal modulates host recovery from respiratory viral infection.

Immunity 2021 06 4;54(6):1200-1218.e9. Epub 2021 May 4.

Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA; Department of Immunology, Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA. Electronic address:

Tissue macrophages self-renew during homeostasis and produce inflammatory mediators upon microbial infection. We examined the relationship between proliferative and inflammatory properties of tissue macrophages by defining the impact of the Wnt/β-catenin pathway, a central regulator of self-renewal, in alveolar macrophages (AMs). Activation of β-catenin by Wnt ligand inhibited AM proliferation and stemness, but promoted inflammatory activity. In a murine influenza viral pneumonia model, β-catenin-mediated AM inflammatory activity promoted acute host morbidity; in contrast, AM proliferation enabled repopulation of reparative AMs and tissue recovery following viral clearance. Mechanistically, Wnt treatment promoted β-catenin-HIF-1α interaction and glycolysis-dependent inflammation while suppressing mitochondrial metabolism and thereby, AM proliferation. Differential HIF-1α activities distinguished proliferative and inflammatory AMs in vivo. This β-catenin-HIF-1α axis was conserved in human AMs and enhanced HIF-1α expression associated with macrophage inflammation in COVID-19 patients. Thus, inflammatory and reparative activities of lung macrophages are regulated by β-catenin-HIF-1α signaling, with implications for the treatment of severe respiratory diseases.
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http://dx.doi.org/10.1016/j.immuni.2021.04.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192557PMC
June 2021

Giant osteochondroma of ilium: a case report and literature review.

Int J Clin Exp Pathol 2021 15;14(4):538-544. Epub 2021 Apr 15.

Department of Orthopaedics, The Affiliated Hospital of Nantong University Nantong City, Jiangsu Province, PR China.

Osteochondroma is one of the most common benign bone tumors. It usually grows on the metaphysis of long bones and rarely develops in bones of scapula, feet, hands, and pelvis. The management of this disease is en-bloc excision of the tumor. We present a 45-year-old female subject, who complained of having found a mass on the right hip for more than 20 years which was diagnosed to be osteochondroma on X-ray, computed tomography (CT) and 3-dimensional (3-D) reconstruction. We performed en-bloc excision for the patient. Pathologic examination of surgical specimen confirmed the diagnosis of osteochondroma. The patient made a complete recovery and there has been no recurrence after one year of follow-up. Osteochondroma usually represents an osteo-cartilaginous aberrant overgrowth of normal epiphyseal growth plates. The disease has a slow onset and a long history. X-rays and CT scans are sufficient for diagnosis before surgery and the final diagnosis should based on pathology. Differential diagnosis includes chondrosarcoma or other neoplasms. When osteochondroma causes pain, compression of peripheral nerves, or continuous growth and other clinical symptoms, en-bloc excision of the tumor is needed. Better recognition and more comprehensive evaluation of these rare cases should be highlighted to avoid misdiagnosis during our clinical practice.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085818PMC
April 2021

Pulmonary Congestion Due to Right and Left Heart Output Mismatching: A Case Report and Literature Review.

Front Physiol 2021 13;12:665483. Epub 2021 Apr 13.

Department of Anesthesiology, Zhongda Hospital, Southeast University, Nanjing, China.

We report a new pulmonary circulation model during cardiopulmonary bypass that is able to cause pulmonary congestion but without left heart failure. This kind of congestion is characterized by right and left heart output mismatching. The pathophysiological mechanism, clinical manifestations, diagnosis, differential diagnosis, and treatment of this pulmonary congestion are reviewed and discussed in the following article.
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http://dx.doi.org/10.3389/fphys.2021.665483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076790PMC
April 2021

Enhancing Performance of Reservoir Computing System Based on Coupled MEMS Resonators.

Sensors (Basel) 2021 Apr 23;21(9). Epub 2021 Apr 23.

The State Key Laboratory of Transducer Technology, Aerospace Information Research Institute, Chinese Academy of Sciences, Beijing 100010, China.

Reservoir computing (RC) is an attractive paradigm of a recurrent neural network (RNN) architecture, owning to the ease of training and existing neuromorphic implementation. Its simulated performance matches other digital algorithms on a series of benchmarking tasks, such as prediction tasks and classification tasks. In this article, we propose a novel RC structure based on the coupled MEMS resonators with the enhanced dynamic richness to optimize the performance of the RC system both on the system level and data set level. Moreover, we first put forward that the dynamic richness of RC comprises linear dynamic richness and nonlinear dynamic richness, which can be enhanced by adding delayed feedbacks and nonlinear nodes, respectively. In order to set forth this point, we compare three typical RC structures, a single-nonlinearity RC structure with single-feedback, a single-nonlinearity RC structure with double-feedbacks, and the couple-nonlinearity RC structure with double-feedbacks. Specifically, four different tasks are enumerated to verify the performance of the three RC structures, and the results show the enhanced dynamic richness by adding delayed feedbacks and nonlinear nodes. These results prove that coupled MEMS resonators offer an interesting platform to implement a complex computing paradigm leveraging their rich dynamical features.
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http://dx.doi.org/10.3390/s21092961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122867PMC
April 2021

Pressure-Induced In Situ Construction of P-CO/HNIW Explosive Composites with Excellent Laser Initiation and Detonation Performance.

ACS Appl Mater Interfaces 2021 May 23;13(17):20718-20727. Epub 2021 Apr 23.

Institute of Chemical Materials, China Academy of Engineering Physics, Mianyang, Sichuan 621900, China.

Laser initiation is a popular research topic in the energetic community. Particularly, the direct ignition of secondary explosives by laser ignitors is considered to be an advanced strategy for enhancing safety and promoting the miniaturization of weapons. Here, to improve the laser sensitivity of secondary explosives, P-CO synthesized under high pressure was employed as a coating for HNIW owing to its laser sensitivity and excellent energetic properties. In this operation, HNIW underwent an obvious isostructural phase transition from the ε-phase to the γ'-phase in the pressure range of 1.0-4.8 GPa. Subsequently, sub-nanoscale HNIW-based composites were formed when CO in situ polymerized to P-CO on the surfaces of HNIW at 5.1 GPa. This HNIW-based composite could be ignited at a much lower laser power (0.49-0.65 W) compared with pure HNIW (2.75-2.98 W) when excited by an Nd:YAG laser with a wavelength of 1064 nm. Additionally, the DFT calculations demonstrated that the arrangement density between HNIW and P-CO was significantly enhanced as the pressure increased. Thus, the introduction of advanced materials into explosive formulations through high-pressure technology is a novel and feasible strategy for developing multipurpose energetic materials.
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http://dx.doi.org/10.1021/acsami.1c03856DOI Listing
May 2021

The synthesis of greenish phosphorus on carbon substrates.

Chem Commun (Camb) 2021 Apr;57(33):3975-3978

Key Laboratory for Green Chemical Technology of Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 457, P. R. China.

A phosphorus allotrope called greenish phosphorus was successfully synthesized via a simple chemical vapor deposition method. We revealed that the critical factors in the formation mechanism of greenish phosphorus are the partial pressure of the phosphorus vapor and the structure of the substrate. On the substrates of a glassy carbon wafer and carbon paper, the edge carbon structure can activate P4 molecules, allowing them to polymerize due to strong adsorption (Ead = -1.62 eV). Greenish phosphorus possesses a distinct crystal structure, different from red phosphorus and black phosphorus, thus leading to unique physical and chemical properties, and potential applications in optical, electrical, and magnetic fields.
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http://dx.doi.org/10.1039/d1cc01419fDOI Listing
April 2021

Circ_0049447 acts as a tumor suppressor in gastric cancer through reducing proliferation, migration, invasion, and epithelial-mesenchymal transition.

Chin Med J (Engl) 2021 Apr 20;134(11):1345-1355. Epub 2021 Apr 20.

Department of Surgical Oncology and General Surgery, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China.

Background: Although increasing abnormal expression of circular RNAs (circRNAs) has been revealed in various cancers, there were a small number of studies about circRNAs in gastric cancer (GC). Here, we explored the expression and function of a novel circRNA, circ_0049447, in GC.

Methods: A total of 80 GC tissues and non-tumorous tissues were collected from the First Affiliated Hospital of China Medical University. And all cells were cultured with 10% fetal bovine serum and incubated at 37°C and 5% CO2. The expression of circ_0049447 was quantified by real-time polymerase chain reaction. The biological function of circ_0049447 on proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) was evaluated by cell counting kit-8 (CCK-8), colony formation assay, transwell migration and invasion assay, and Western blotting. Luciferase report assay was used to verify the direct binding between circ_0049447 and predicted microRNA (miRNA). Furthermore, a xenograft mouse model was used to validate the function of circ_0049447 in vivo.

Results: We demonstrated that circ_0049447 was downregulated in GC (P < 0.001). The area under the receiver operating characteristic curve reached 0.838, while sensitivity was 82.3% and specificity was 77.2%. CCK-8 and colony formation assay showed that overexpression of circ_0049447 could inhibit the proliferation (P < 0.05). Transwell migration and invasion assay showed upregulated circ_0049447 could impede migration in GC cells (P < 0.05). In addition, overexpression of circ_0049447 could impede GC cell EMT. Upregulation of miR-324-5p in GC specimens and direct binding between miR-324-5p with circ_0049447 proven by luciferase reporter assay indicated that circ_0049447 may inhibit GC by sponging certain miRNA.

Conclusion: Circ_0049447 acts as a tumor suppressor in GC through reducing proliferation, migration, invasion, and EMT, and it is a promising biomarker for diagnosis.
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http://dx.doi.org/10.1097/CM9.0000000000001494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183756PMC
April 2021

Positive impact of oral hydroxychloroquine and povidone-iodine throat spray for COVID-19 prophylaxis: An open-label randomized trial.

Int J Infect Dis 2021 May 20;106:314-322. Epub 2021 Apr 20.

Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.

Background: We examined whether existing licensed pharmacotherapies could reduce the spread of coronavirus disease 2019 (COVID-19).

Methods: An open-label parallel randomized controlled trial was performed among healthy migrant workers quarantined in a large multi-storey dormitory in Singapore. Forty clusters (each defined as individual floors of the dormitory) were randomly assigned to receive a 42-day prophylaxis regimen of either oral hydroxychloroquine (400 mg once, followed by 200 mg/day), oral ivermectin (12 mg once), povidone-iodine throat spray (3 times/day, 270 μg/day), oral zinc (80 mg/day)/vitamin C (500 mg/day) combination, or oral vitamin C, 500 mg/day. The primary outcome was laboratory evidence of SARS-CoV-2 infection as shown by either: (1) a positive serologic test for SARS-CoV-2 antibody on day 42, or (2) a positive PCR test for SARS-CoV-2 at any time between baseline and day 42.

Results: A total of 3037 asymptomatic participants (mean age, 33.0 years; all men) who were seronegative to SARS-CoV-2 at baseline were included in the primary analysis. Follow-up was nearly complete (99.6%). Compared with vitamin C, significant absolute risk reductions (%, 98.75% confidence interval) were observed for oral hydroxychloroquine (21%, 2-42%) and povidone-iodine throat spray (24%, 7-39%). No statistically significant differences were observed with oral zinc/vitamin C combination (23%, -5 to +41%) and ivermectin (5%, -10 to +22%). Interruptions due to side effects were highest among participants who received zinc/vitamin C combination (6.9%), followed by vitamin C (4.7%), povidone-iodine (2.0%), and hydroxychloroquine (0.7%).

Conclusions: Chemoprophylaxis with either oral hydroxychloroquine or povidone-iodine throat spray was superior to oral vitamin C in reducing SARS-CoV-2 infection in young and healthy men.
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http://dx.doi.org/10.1016/j.ijid.2021.04.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056783PMC
May 2021