Publications by authors named "Qiang Sun"

961 Publications

Prospective assessment of breast cancer risk from multimodal multiview ultrasound images via clinically applicable deep learning.

Nat Biomed Eng 2021 Apr 19. Epub 2021 Apr 19.

Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA.

The clinical application of breast ultrasound for the assessment of cancer risk and of deep learning for the classification of breast-ultrasound images has been hindered by inter-grader variability and high false positive rates and by deep-learning models that do not follow Breast Imaging Reporting and Data System (BI-RADS) standards, lack explainability features and have not been tested prospectively. Here, we show that an explainable deep-learning system trained on 10,815 multimodal breast-ultrasound images of 721 biopsy-confirmed lesions from 634 patients across two hospitals and prospectively tested on 912 additional images of 152 lesions from 141 patients predicts BI-RADS scores for breast cancer as accurately as experienced radiologists, with areas under the receiver operating curve of 0.922 (95% confidence interval (CI) = 0.868-0.959) for bimodal images and 0.955 (95% CI = 0.909-0.982) for multimodal images. Multimodal multiview breast-ultrasound images augmented with heatmaps for malignancy risk predicted via deep learning may facilitate the adoption of ultrasound imaging in screening mammography workflows.
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http://dx.doi.org/10.1038/s41551-021-00711-2DOI Listing
April 2021

Clinical and Genetic Characteristics of Atypical Hemolytic Uremic Syndrome in Children: A Chinese Cohort Study.

Nephron 2021 Apr 19:1-13. Epub 2021 Apr 19.

Department of Nephrology, Beijing Children's Hospital, Capital Medical University, Beijing, China.

Background: Atypical hemolytic uremic syndrome (aHUS) is a rare but critical illness. To this date, few studies have reported on the disease in Chinese children.

Methods: We studied a Chinese pediatric cohort to delineate the clinical characteristics, genotypes, and prognosis. Ninety-one patients with aHUS were enrolled in this study.

Results: Fifty-nine children (64.8%) had anti-complement-factor-H autoantibody-associated aHUS (anti-CFH aHUS). Of these children, 21 (46.7%) had complement factor-H-related protein 1 (CFHR1) homozygous deletion, and most patients with CFHR1 homozygous deletion also had complement factor-H-related protein 3 (CFHR3) homozygous deletions (76.2%). Using gene sequencing of 15 candidate genes, we identified 14 genetic variants in 46 aHUS patients, including 5 pathogenic or like pathogenic variants and 9 variants of uncertain significance. The average follow-up time was 46.1 ± 28 months. Among patients with anti-CFH aHUS, there was a correlation between CFHR1 homozygous deletion and patients with persistent proteinuria (odds ratio [OR] 6.954, 95% confidence interval [CI] 1.033-46.821, p = 0.046). As of the last follow-up, ESRD or deaths occurred in 3.6% of the children with anti-CFH aHUS and 26.7% of children with aHUS who were negative for anti-CFH.

Conclusions: Anti-complement-factor-H antibody positivity is the main cause of morbidity in Chinese children with aHUS. There may be a correlation between CFHR1 homozygous deletion and persistent proteinuria. Comprehensive assessment of anti-CFH antibodies and genetic variants is essential for the management of aHUS children.
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http://dx.doi.org/10.1159/000513009DOI Listing
April 2021

A Sociocultural Perspective on English-as-a-Foreign-Language (EFL) Teachers' Cognitions About Form-Focused Instruction.

Front Psychol 2021 31;12:593172. Epub 2021 Mar 31.

Faculty of Education and Social Work, University of Auckland, Auckland, New Zealand.

There has been much research into teacher beliefs about teaching and learning as seen in the general teacher education literature. In the field of language teacher education, this line of research has been evolving, with the recent trend being streamlined into "teacher cognition" as a generic or umbrella term. Despite increasing amounts of research output so far, research into foreign language teachers' cognitions about their own teaching and decision-making is still insufficient, particularly with regard to university-level English-as-a-foreign-language (EFL) teachers in China. Drawing on Vygotsky's Sociocultural Theory, this qualitative research focused on EFL teachers' cognitions about form-focused instruction in Chinese university settings. It intended to discover how teachers' cognitions changed when they were expected to teach in actual classrooms and what factors contributed to these changes. Data collected from four teacher-participants through semi-structured interviews, classroom observations and follow-up stimulated recall interviews showed participants' support for instruction, which means they not only paid attention to the grammatical form of the language but also to the meaning it is intended to convey. However, data also showed that the teacher-participants shifted from to instruction in actual teaching, which suggests that they might have realized the challenges of carrying out teaching activities surrounding and would like to take an easier approach by only teaching the grammar of the language by . Such incongruences are interpreted with reference to a plethora of sociocultural factors including traditional Chinese thinking and institutional expectations. The implications of the findings for stakeholders in universities, including faculty members, students, and curriculum developers in similar contexts, are also discussed.
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http://dx.doi.org/10.3389/fpsyg.2021.593172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044539PMC
March 2021

T1a triple negative breast cancer has the worst prognosis among all the small tumor (<1 cm) of TNBC and HER2-rich subtypes.

Gland Surg 2021 Mar;10(3):943-952

Department of Breast Surgery, Peking Union Medical College Hospital, Beijing, China.

Background: Triple negative breast cancer (TNBC), accounting for 15% of all breast cancer cases, was usually considered as the most aggressive subtype. The present study evaluated the prognosis of T1a TNBC and the impact of tumor size on T1 TNBC survival in large-scale population.

Methods: This retrospective study enrolled T1a/T1b/T1c TNBC and HER2/hormone receptor (HoR) patients diagnosed between 2010 to 2012 from the Surveillance, Epidemiology, and End Results database. The following information was extracted for further analyses: demographic variables including age at diagnosis, race, marital status, laterality, histological grade, T/N stage, American Joint Committee on Cancer (AJCC) stage, radiation therapy, survival and cause of death. Kaplan-Meier method and Cox regression were engaged for breast cancer specific survival (BCSS) and overall survival (OS) analyses.

Results: In all, the present study enrolled 6,953 TNBC and 2,648 HER2/HoR patients. T1a TNBC which generally omitted adjuvant chemotherapy had worse prognosis than T1a HER2/HoR [BCSS: hazard ratio (HR) 3.23, 95% confidence interval (CI): 1.05-9.09, P=0.03; OS: HR 2.63, 95% CI: 1.25-5.56, P=0.01] and T1b HER2/HoR (BCSS: HR 5.26, 95% CI: 1.61-16.7, P=0.006; OS: HR 3.03, 95% CI: 1.27-7.14, P=0.013) tumors which both were recommended by the National Comprehensive Cancer Network (NCCN) guideline to have chemotherapy. T1a TNBC also showed a trend with poorer prognosis than T1b TNBC, but did not reach statistical significance.

Conclusions: T1a TNBC had the worst prognosis among all small tumors (<1 cm) of TNBC and HER2/HoR subtypes, indicating the necessity of more intensive adjuvant treatment.
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http://dx.doi.org/10.21037/gs-20-762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033067PMC
March 2021

Current Status of MicroRNAs that Target the Wnt Signaling Pathway in Regulation of Osteogenesis and Bone Metabolism: A Review.

Med Sci Monit 2021 Apr 8;27:e929510. Epub 2021 Apr 8.

Department of Plastic Surgery, The First Hopital of China Medical University, Shenyang, Liaoning, China (mainland).

The directional differentiation of bone mesenchymal stem cells (BMSCs) is regulated by a variety of transcription factors and intracellular signaling pathways. In the past, it was thought that the directional differentiation of BMSCs was related to transforming growth factors, such as bone morphogenetic protein (BMP) and MAPK pathway. However, in recent years, some scholars have pointed out that the Wnt signaling pathway, which is a necessary complex network of protein interactions for biological growth and development, takes a significant role in this process and plays a major part in regulating the development of osteoblasts by exerting signal transduction into cells. Also, they have proved the Wnt protein therapeutic truly have positive effects on the viability and osteogenic capacity of bone graft. Recent studies have shown that microRNAs (miRNAs) play an important regulatory role in this process. MiRNAs such as miRNA-218, miRNA-335, miRNA-29, microRNA-30 and other miRNAs exert negative or positive effects on some crucial molecules in the Wnt/ß-catenin pathway, which in turn affect bone metabolism and osteopathy. Thus, miRNAs have been suggested as therapeutic targets for some metabolic bone diseases. This article aims to provide an update on the current status of microRNAs that target the Wnt signaling pathway in the regulation of osteogenesis and bone metabolism and includes a discussion of future areas of research, which can be a theoretical basis for bone metabolism-related diseases.
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http://dx.doi.org/10.12659/MSM.929510DOI Listing
April 2021

Colorectal Cancer, Gut Microbiota and Traditional Chinese Medicine: A Systematic Review.

Am J Chin Med 2021 Apr 6:1-24. Epub 2021 Apr 6.

State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.

Based on the study and research on the pathogenesis of colorectal cancer, the types and functions of gut microbiota, and its role in guiding and regulating the occurrence and development of diseases, we have explored the mechanism of traditional Chinese medicine in the treatment of colorectal cancer by regulating the gut microbiota. Genetic variation, abnormal responses of innate and adaptive immunity, mucosal barrier dysfunction, imbalance of intestinal microbial colonization, personal and environmental risk factors are the main pathogenesis of colorectal cancer. The gut microbiota mainly includes (including , , and ) and (including and ), which have biological antagonism, nutrition for the organism, metabolic abilities, immune stimulation, and ability to shape cancer genes functions to body. The gut microbiota can be related to the health of the host. Current studies have shown that Chinese herbal compound, single medicinal materials, and monomer components can treat colorectal cancer by regulating the gut microbiota, such as Xiaoyaosan can increase the abundance of , , and and decrease the abundance of and . Therefore, studying the regulation and mechanism of gut microbiota on colorectal cancer is of great benefit to disease treatment.
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http://dx.doi.org/10.1142/S0192415X21500385DOI Listing
April 2021

[Mechanism of ursolic acid in regulating colorectal cancer cell HCT116 autophagy through hedgehog signaling pathway].

Zhongguo Zhong Yao Za Zhi 2021 Mar;46(5):1217-1223

Department of Pharmacology,School of Pharmacy,Chengdu University of Traditional Chinese Medicine Chengdu 611137,China.

To prove that ursolic acid(UA)could activate the autophagy of colorectal cancer HCT116 cells by inhibiting hedgehog signaling pathway. The effect of UA on the viability of HCT116 cells was determined by MTT assay. The effect of UA on the proliferation and migration of HCT116 cells was detected by crystal violet staining and scratch test. In the study on autophagy, the time points were screened out first: the autophagy fluorescence intensity of UA acting on HCT116 at different time points were detected by Cell Meter~(TM) Autophagy Assay Kit; Western blot was used to detect the expression of autophagy protein P62 at different time points. Then, Cell Meter~(TM) Autophagy Assay Kit was used to detect the effect of UA on autophagy fluorescence intensity of HCT116 cells. The effect of different doses of UA on the expressions of LC3Ⅱ and P62 proteins in HCT116 cells were detected by Western blot. Further, AdPlus-mCherry-GFP-LC3 B adenovirus transfection was used to detect the effects of UA on autophagy flux of HCT116 cells; UA combined with autophagy inhibitor chloroquine(CQ) was used to detect the expression of LC3Ⅱ by Western blot. In terms of mechanism, the effect of UA on hedgehog signaling pathway-related proteins in HCT116 cells was detected by Western blot. The results showed that UA inhibited the activity, proliferation and migration of HCT116 cells. UA enhanced the fluorescence intensity of autophagy in HCT116 cells, while promoting the expression of LC3Ⅱ and inhibiting the expression of P62, in a time and dose dependent manner. UA activated the autophagy in HCT116 cells, which manifested that UA resulted in the accumulation of fluorescence spots and strengthened the fluorescence intensity of autophagosomes; compared with UA alone, UA combined with autophagy inhibitor CQ promoted the expression of LC3Ⅱ. UA reduced the expressions of PTCH1, GLI1, SMO, SHH and c-Myc in hedgehog signaling pathway, while increased the expression of Sufu. In conclusion, our study showed that UA activated autophagy in colorectal cancer HCT116 cells, which was related to the mechanism in inhibiting hedgehog signaling pathway activity.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20201207.403DOI Listing
March 2021

Tubular epithelial cells derived-exosomes containing CD26 protects mice against renal ischemia/reperfusion injury by maintaining proliferation and dissipating inflammation.

Biochem Biophys Res Commun 2021 May 24;553:134-140. Epub 2021 Mar 24.

The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; Department of Critical Care Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China. Electronic address:

Ischemia-reperfusion injury (IR) is the leading cause of acute kidney injury (AKI). No effective drugs to treat IR-related AKI are currently available. Recent pre-clinical trials have evaluated the therapeutic potential of extracellular vesicles-exosomes to chronic kidney disease. Here, we found exosomes derived from the tubular epithelial cell in IR condition (Exo) enriched CD26, compared with control (Exo). Tracking exosomes in vivo certified tubular epithelial cell uptake exosomes. We have isolated exosomes with overexpression of CD26 (Exo) from culture media from tubular epithelial cell line transferred by adenovirus vectors. After administration of exosomes (100 mg) or bovine serum albumin (BSA, equivalent protein control) in IR or sham operation mice after 72 h via tail vein injection, the renal function impairment and histology injury were relived in mice receiving Exo. Immunofluorescence staining with proliferating cell nuclear antigen revealed Exo recovered proliferation of cells partly after IR injury. Cell cycle modulator, p53 and p21 were upregulated in IR mice receiving BSA control, Exo, and Exo. Exo significantly blunt this protein upregulation. Inflammatory cell infiltration and chemokine receptor (CXCR4) were dissipated in IR mice receiving Exo. Downstream chemokine of CXCR4, stromal derived factor-1 (SDF1) also decreased after administration of Exo in IR mice. Finally, Exo suppressed inundant collagenⅠ expression in IR kidney. In conclusion, Tubular epithelial cells derived-exosomes containing CD26 might be one of the therapy modes for IR-AKI by maintaining proliferation and dissipating inflammation.
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http://dx.doi.org/10.1016/j.bbrc.2021.03.057DOI Listing
May 2021

linc‑ROR facilitates hepatocellular carcinoma resistance to doxorubicin by regulating TWIST1‑mediated epithelial‑mesenchymal transition.

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

Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China.

Long non‑coding RNAs are associated with cancer progression. Long intergenic non‑protein coding RNA (linc)‑regulator of reprogramming (ROR) enhances tumor development in hepatocellular carcinoma (HCC). However, the effect of chemoresistance and its underlying mechanisms in HCC are not completely understood. The present study aimed to identify the effect of ROR on sensitivity to doxorubicin (DOX) in HCC cells. In the present study, Cell Counting Kit‑8 and EdU assays were performed to assess cell viability and proliferation, respectively. In addition, E‑cadherin and vimentin protein expression levels were assessed via western blotting and immunofluorescence.The results of the present study demonstrated that HCC cells with high linc‑ROR expression levels were more resistant to DOX, and linc‑ROR knockdown increased HCC cell DOX sensitivity compared with the control group. The results indicated that compared with the NC siRNA group, linc‑ROR knockdown notably suppressed epithelial‑mesenchymal transition by downregulating twist family bHLH transcription factor 1 (TWIST1) expression. TWIST1 knockdown displayed a similar effect on HCC cell DOX sensitivity to linc‑ROR knockdown. Moreover, linc‑ROR knockdown‑induced HCC cell DOX sensitivity was inhibited by TWIST1 overexpression. The present study provided evidence that linc‑ROR promoted HCC resistance to DOX by inducing EMT via interacting with TWIST1. Therefore, linc‑ROR might serve as a therapeutic target for reducing DOX resistance in HCC.
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http://dx.doi.org/10.3892/mmr.2021.11979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7974311PMC
May 2021

Mismatch Repair Deficiency and Microsatellite Instability in Triple-Negative Breast Cancer: A Retrospective Study of 440 Patients.

Front Oncol 2021 4;11:570623. Epub 2021 Mar 4.

Department of Pathology, State Key Laboratory of Complex Severe and Rare Diseases, Molecular Pathology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.

Purpose: To investigate the status of mismatch repair (MMR) and microsatellite instability (MSI) in triple-negative breast cancer (TNBC) and to examine correlations between MMR/MSI status and clinicopathological parameters.

Methods: We retrospectively collected tissue samples from 440 patients with TNBC and constructed tissue microarrays. Protein expression of MLH1, MSH2, MSH6, and PMS2 was detected by immunohistochemistry (IHC). We also analyzed 195 patient samples using MSI polymerase chain reaction (PCR) testing. Correlations between MSI status and clinicopathological parameters and prognosis were analyzed.

Results: The median age of the cohort was 49 years (range: 24-90 years) with a median follow-up period of 68 months (range: 1-170 months). All samples were positive for MLH1, MSH2, MSH6, and PMS2, except for one sample identified as MMR-deficient (dMMR) by IHC, with loss of MSH2 and intact MSH6 expression. MSI PCR revealed no case with high-frequency MSI (MSI-H), whereas 14 (7.2%) and 181 (92.8%) samples demonstrated low-frequency and absence of MSI events, respectively. The dMMR sample harbored low-frequency instability, as revealed by MSI PCR, and a possible deletion in the tumor, as observed from next-generation sequencing. No correlations were detected between MMR or MSI status and clinicopathological parameters, programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) expression, or survival.

Conclusions: The incidence of dMMR/MSI-H is extremely low in TNBC, and rare discordant MSI PCR/MMR IHC results may be encountered. Moreover, MMR/MSI status may be of limited prognostic value. Further studies are warranted to explore other predictive immunotherapy biomarkers for TNBC.
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http://dx.doi.org/10.3389/fonc.2021.570623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970194PMC
March 2021

Efficacy of apatinib as third-line treatment of advanced colorectal cancer and prognostic analysis.

J BUON 2021 Jan-Feb;26(1):93-100

Department of Medical Oncology, Shengzhou People's Hospital (Shengzhou branch, the First Affiliated Hospital of Zhejiang University), Shengzhou, China.

Purpose: To explore the efficacy and safety of apatinib mesylate in the third-line treatment of advanced colorectal cancer after the standard second-line treatment failed, and to analyze the possible factors affecting the prognosis.

Methods: The clinical data of 52 patients with advanced colorectal cancer who failed or were intolerant of the standard second-line treatment performed in our hospital from January 2017 to December 2018 were collected. All the patients received the third-line treatment with apatinib mesylate tablets that were administered at 500 mg q.d. with 28 d as an administration cycle, and the clinical efficacy of apatinib mesylate and incidence of adverse reactions were recorded and analyzed. Besides, the survival and disease progression of the patients were followed up and recorded, and the influencing factors for the prognosis were analyzed.

Results: The remaining 50 patients had efficacy evaluation, and it was found that the overall response rate (ORR) and disease control rate (DCR) were 8.0% (4/50) and 50% (25/50), respectively. The median survival, median progression-free survival (mPFS) and 1-year overall survival (OS) rate were 7.6±2.5, 4.0±1.7 and 26.9% (14/52), respectively. After treatment, the patients had increased scores for all items on the functional scale of the Quality of Life Questionnaire Core 30 (QLQ-C30). Decreases in the scores for all items on the symptomatic scale were also found after treatment, and the mitigation of the symptoms nausea and vomiting and pain was statistically significantly different. According to multivariate analysis results, the mPFS was significantly prolonged in the patients with CerB2++/+++, the positivity rate of Ki-67 ≥50% and the presence of hypertension after treatment.

Conclusions: Apatinib is effective in the third-line treatment of advanced colorectal cancer, significantly improves the patient quality of life, and causes tolerable adverse reactions. The mPFS is markedly extended in the patients with CerB2++/+++, positivity rate of Ki-67 ≥50% and the presence of hypertension after treatment, which are the independent factors affecting the efficacy.
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March 2021

SHCBP1 Promotes Papillary Thyroid Carcinoma Carcinogenesis and Progression Through Promoting Formation of Integrin and Collagen and Maintaining Cell Stemness.

Front Endocrinol (Lausanne) 2020 26;11:613879. Epub 2021 Feb 26.

Department of Endocrinology, Affiliated Hospital of Medical College of Southeast University and Xuzhou Central Hospital, Xuzhou, China.

Papillary thyroid carcinoma (PTC) is the most common thyroid cancer with a rapidly increasing incidence globally. Bioinformatics analyses suggested that SHCBP1 (SHC SH2 Domain-Binding Protein 1) was significantly up-regulated in PTC tumor tissues, which was further confirmed by immunohistochemical staining and qPCR analyses in Xuzhou cohort. Moreover, the results indicated that the mRNA level of was negatively associated with patients' disease-free survival rate, and further analysis reveals that patients with high SHCBP1 expression tend to have more lymph node metastasis. Afterward, MTT, colony formation, cell-cycle assay, FACS apoptosis assay, invasion, migration, as well as scratch assay were performed to study the phenotypes change of PTC cells after knocking down SHCBP1. The subcutaneous tumor model was developed to study the proliferation ability of PTC cells after SHCBP1 knockdown. We show that knock down of SHCBP1 significantly inhibits PTC cell proliferation, cell cycle, invasion and migration and . Western blot and qRT-PCR showed that knockdown of SHCBP1 could significantly reduce MYC, KLF4, CD44, ITGA6, ITGB1, ITGB5, and COL4A2 expression at both RNA and protein levels, which indicated that SHCBP1 might be involved in PTC carcinogenesis and progression through targeting formation of integrin and collagen and cell stemness pathways, and can be a potential diagnosis biomarker and therapeutic target for PTC.
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http://dx.doi.org/10.3389/fendo.2020.613879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953042PMC
February 2021

Tall cell carcinoma of the breast with reverse polarity: case report with gene sequencing and literature review.

Gland Surg 2021 Feb;10(2):837-843

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

Tall cell carcinoma of the breast with reverse polarity (TCCRP), described firstly and also known as tall cell variant of papillary breast carcinoma (TCVPBC), is a rare type of breast cancer that mimics papillary thyroid carcinoma (PTC) histopathologically. As the incidence of this type of tumor is very low, awareness of it is crucial to ensuring that unnecessary clinical investigations are avoided. The present study examined a 45-year-old woman in China who was diagnosed with TCCRP. This paper outlines her demographic and clinicopathologic data, and her follow-up and immunohistochemical examination results. Furthermore, this study used the next-generation sequencing (NGS) technique to identify concurrent isocitrate dehydrogenase 2 (IDH2) and phosphatidylinositol 3-kinase catalytic alpha (PIK3CA) hotspot mutations. Notably, the novel results of the study showed that the IDH2 R120 (rather than the IDH2 R172) mutation may also be present in this disease. Additionally, a comprehensive literature review was conducted to elucidate some of the significant clinical and pathological features of this type of disease. This information may provide important insights that can be used in diagnosis and treatment. It is essential both for physicians and pathologists to recognize the existence of TCCRP, with its own specific clinical and pathological characteristics. Further research using molecular biology techniques should be conducted in the future to characterize this unique entity.
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http://dx.doi.org/10.21037/gs-20-695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944084PMC
February 2021

Molecular mechanisms underlying cell-in-cell formation: core machineries and beyond.

J Mol Cell Biol 2021 Mar 6. Epub 2021 Mar 6.

Laboratory of Cell Engineering, Institute of Biotechnology, Beijing 100071, China.

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http://dx.doi.org/10.1093/jmcb/mjab015DOI Listing
March 2021

The Effectiveness of an Educational Intervention on Knowledge, Attitudes and Reported Practices on Antibiotic Use in Humans and Pigs: A Quasi-Experimental Study in Twelve Villages in Shandong Province, China.

Int J Environ Res Public Health 2021 Feb 17;18(4). Epub 2021 Feb 17.

Department of Global Public Health, Karolinska Institutet, 17177 Stockholm, Sweden.

Our aim was to evaluate the effectiveness of an intervention for residents in rural China on knowledge, attitudes and reported practices (KAP) on antibiotic use in humans and pigs. A quasi-experimental study was conducted in 12 villages in rural Shandong province, divided into intervention and control groups, covering a two-year period from July 2015 to June 2017. A package of health education-based interventions including training sessions, speakerphone messages, posters and handbooks for residents was developed and implemented over a one-year period to improve the use of antibiotics in humans and pigs. The intervention net effects were evaluated by Difference-in-Difference (DID) analysis based on responses to a questionnaire concerning KAP towards antibiotic use in humans and pigs. A total of 629 participants completed both baseline and post-trial questionnaires, including 127 participants with backyard pig farms. Significant improvements were found in KAP towards antibiotic use in humans, but changes related to antibiotic use for pigs were not significant. Participants who were in the intervention group ( < 0.001) were more likely to have improved their knowledge on antibiotic use in humans. Participants who had higher attitude scores were less likely to report self-medicating with stored antibiotics in the previous year ( < 0.001). Our results suggest that our health education-based intervention was effective in improving KAP on human antibiotic use, but it had little effect regarding antibiotic use for pigs.
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http://dx.doi.org/10.3390/ijerph18041940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922583PMC
February 2021

Understanding the Profiles of Blood Glucose Monitoring Among Patients with Type 2 Diabetes Mellitus: A Cross-Sectional Study in Shandong, China.

Patient Prefer Adherence 2021 22;15:399-409. Epub 2021 Feb 22.

Endocrinology Department, Jinan Central Hospital Affiliated to Shandong University, Jinan, People's Republic of China.

Background: Blood glucose monitoring is essential in diabetic care and management. Monitoring using glucometers in home and in laboratories by professionals in certain health institutes were the common methods of blood glucose monitoring in clinical practice. This study aimed to characterize the profiles of blood glucose monitoring in the view of the discrepancy in methods and frequency conducted by the patients with type 2 diabetes mellitus (T2DM) in China, and to explore factors influencing the profiles.

Methods: A cross-sectional, community-based study was conducted in Shandong province, China, with a multi-stage stratified sampling. A total of 2166 T2DM patients completed the structured questionnaires about the real-world status of blood glucose monitoring and other questions composed of demographic and clinical characteristic as well as the diabetes-related cognitive scales. Latent profile analysis (LPA) was used to identify the underlying profiles of blood glucose monitoring based on self-reported frequency of blood glucose monitoring through different methods. Univariate and multivariate logistic regression were used to analyze the characteristics of the profiles and to explore the factors associated with it.

Results: Among the 2166 participants, the mean frequency of blood glucose monitoring was 2.77 times (standard deviation: 7.67) per month. LPA indicated that five-class model was the best solution for classifying the latent groups of blood glucose monitoring: Class 1 "Low frequency in all", Class 2 "High frequency in hospitals", Class 3 "High frequency in primary health institutes", Class 4 "High frequency in pharmacies", and Class 5 "High frequency in self-monitoring". The proportions of the patients in class 1, class 2, class 3, class 4, and class 5 were 88.1% (n=1909), 1.3% (n=28), 3.1% (n=67), 6.1% (n=133) and 1.3% (n=29), respectively. Multivariate logistic regression showed that participants who had higher income (OR: 1.58, 95% CI: 1.04~2.41, p<0.05), had diabetes complication(s) (OR=1.37, 95% CI: 1.03~1.02, p=0.03) and had a good knowledge of blood glucose control (OR=1.59, 95% CI: 1.17~2.16, p<0.01) were more likely to have high frequency of blood glucose monitoring (in class 2, 3, 4, 5), and the rural patients were less likely to had high frequency of blood glucose monitoring (OR=0.47, 95% CI: 0.35~0.63, p<0.01).

Conclusion: Low frequency dominates the characteristics of the profiles of blood glucose monitoring among T2DM patients in China, though distinct blood glucose monitoring groups can be identified by LPA. Educational and financial supports were recommended to increase the frequency of blood glucose monitoring in patients with T2DM, focusing on the patients with low socioeconomic status.
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http://dx.doi.org/10.2147/PPA.S292086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910106PMC
February 2021

Cancer-derived exosomal miR-7641 promotes breast cancer progression and metastasis.

Cell Commun Signal 2021 Feb 22;19(1):20. Epub 2021 Feb 22.

Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China.

Background: Intercellular communication is crucial for breast cancer progression and metastasis. However, the role of cancer-derived exosomes and their crucial microRNA (miRNA) cargoes mediating intercellular communication requires further investigation.

Methods: Cancer-derived exosomes were isolated using differential centrifugation and differentially expressed miRNAs were determined by microarrays and qRT-PCR analysis. Cell proliferation, wound-healing, Transwell invasion, and tumor xenograft assays were used for functional research. Plasma exosomal RNA was isolated to verify its role as a prognostic biomarker.

Results: We found that the tumor-promoting capacity of the exosomes was positively related to their cells of origin. MiR-7641 was identified to be the most differentially expressed miRNA, both at endogenous and secretory levels in high-metastatic cancer cells. MiR-7641 could promote tumor cell progression and metastasis, and that these functions of miR-7641 could alter recipient cells via transportation of exosomes. Additionally, exosomal miR-7641 could promote tumor growth in vivo; and its levels were significantly elevated in the plasma of patients with distant metastasis. Bioinformatics analysis has suggested that miR-7641 is correlated with breast cancer survival, and several important cellular and biological processes are closely targeted by miR-7641.

Conclusion: The findings indicate miR-7641 to be an important component of the cancer exosomes in promoting tumor progression and metastasis via intercellular communication. Additionally, exosomal miR-7641 may serve as a promising non-invasive diagnostic biomarker and potential targetable candidate in breast cancer treatment. Video Abstract.
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http://dx.doi.org/10.1186/s12964-020-00700-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898766PMC
February 2021

Ribosomal Protein SA-Positive Neutrophil Elicits Stronger Phagocytosis and Neutrophil Extracellular Trap Formation and Subdues Pro-Inflammatory Cytokine Secretion Against Serotype 2 Infection.

Front Immunol 2020 2;11:585399. Epub 2021 Feb 2.

College of Veterinary Medicine, Jilin University, Changchun, China.

serotype 2 (SS2), an important zoonotic pathogen that causes septicemia, arthritis, and irreversible meningitis in pigs and humans, can be transmitted to humans from pigs. causes huge economic losses to the swine industry and poses a serious threat to public health. Previously, we found that the brain tissues of mice with SS2-induced meningitis showed disrupted structural integrity and significantly enhanced polymorphonuclear neutrophil (PMN) infiltration. We showed that the brain tissues of SS2-infected mice had increased ribosomal protein SA (RPSA)-positive PMN counts. However, the inflammatory responses of RPSA PMNs to SS2 and their effects on the blood-brain barrier (BBB) remain unclear. Therefore, in studying the pathogenesis of SS2-induced meningitis, it is essential that we explore the functions of RPSA PMNs and their effects on the BBB. Herein, using flow cytometry and immunofluorescence microscopy analyses, we found that RPSA expression enhances PMN-induced phagocytosis and PMN-induced formation of neutrophil extracellular traps (NETs), which facilitate further elimination of bacteria. PMN surface expression of RPSA also alleviates local inflammation and tissue injuries by inhibiting secretion of the pro-inflammatory cytokines, TNF-α and IL-6. Moreover, the single-cell BBB model showed that RPSA disrupts BBB integrity by downregulating expression of tight junction-associated membrane proteins on PMNs. Taken together, our data suggest that PMN-surface expression of RPSA is a double-edged sword. RPSA+ PMN owns a stronger ability of bacterial cleaning and weakens inflammatory cytokines release which are useful to anti-infection, but does hurt BBB. Partly, RPSA+ PMN may be extremely useful to control the infection as a therapeutic cellular population, following novel insights into the special PMN population.
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http://dx.doi.org/10.3389/fimmu.2020.585399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884477PMC
February 2021

Dual-enzyme hydrolysis for preparation of ACE-inhibitory peptides from sesame seed protein: Optimization, separation, and identification.

J Food Biochem 2021 Feb 5:e13638. Epub 2021 Feb 5.

Research Center for Agricultural and Sideline Products Processing, Henan Academy of Agricultural Sciences, Zhengzhou, 450002, P.R. China.

To prepare and identify ACE-inhibitory peptides originated from sesame seed protein, peptides with strong ACE-inhibitory activities were obtained via the optimization of protease and hydrolysis conditions, and these peptides were purified and identified by membrane separation, gel filtration, and liquid chromatography-mass spectrometry. Results showed that the dual-enzyme comprised alcalase and trypsin with the enzyme activity ratio of 3:7 was suitable to produce ACE-inhibitory peptides. The highest ACE-inhibitory activity of 98.10 ± 0.26% was obtained at the following parameters, pH 8.35, E/S ratio of 6,145 U/g, and hydrolysis time of 4.4 hr. ISGAQPSLR and VVISAPSK ranked the first and second ACE-inhibitory activity among 15 identified ACE-inhibitory peptides. Both peptides influenced ACE via binding with the S1 pocket, S2 pocket, and Zn ion. ISGAQPSLR even impacted the S1' pocket. ISGAQPSLR and VVISAPSK acted as a competitive and noncompetitive inhibitor, respectively. ACE-inhibitory peptides derivated from sesame seed protein have potential applications in functional food. PRACTICAL APPLICATIONS: Although sesame seed protein is proven as the precursor of ACE-inhibitory peptide, preparing ACE-inhibitory peptide from sesame seed protein is still suffering from insufficient information on hydrolysis condition and the peptide sequence. Therefore, the performance of the typical protease on preparing ACE-inhibitory peptide from sesame seed protein has been evaluated, the effect of the amino acid composition of sesame seed protein and cleavage specificity of protease on the generation of ACE-inhibitory peptide has been investigated, hydrolysis conditions have been optimized, the peptide sequence has been identified to illuminate the effect of sesame seed protein fraction on the formation of ACE-inhibitory peptide and discuss the structural characteristics. ACE-inhibitory peptides originating from sesame seed protein could apply in functional food. It is promising for dual-enzyme hydrolysis to utilize in preparation of high-value bioactive peptides.
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http://dx.doi.org/10.1111/jfbc.13638DOI Listing
February 2021

B Cluster-Based 3D Porous Topological Metal as an Anode Material for Both Li- and Na-Ion Batteries with a Superhigh Capacity.

J Phys Chem Lett 2021 Feb 3;12(5):1548-1553. Epub 2021 Feb 3.

School of Materials Science and Engineering, Peking University, Beijing, China.

The high rate performance of a battery requires the anode to be conductive not just ionically but also electronically. This criterion has significantly stimulated the study on 3D porous topological metals composed of nonmetal atoms with a light mass. Many carbon-based 3D topological metals for batteries have been reported, while similar work for 3D boron remains missing. Here, we report of a 3D boron topological metal as an anode material for Li or Na ions. Based on systematic calculations, we found that the reported 3D topological metal H-boron composed of B cluster shows a low mass density (0.91 g/cm) with multiple adsorption sites for Li and Na ions due to the electron-deficient feature of boron, leading to an ultrahigh specific capacity of 930 mAh/g for Li and Na ions with a small migration barrier of 0.15 and 0.22 eV, respectively, and small volume changes of 0.6% and 9.8%. These intriguing features demonstrate that B-based 3D topological quantum porous materials are worthy of further study for batteries.
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http://dx.doi.org/10.1021/acs.jpclett.0c03709DOI Listing
February 2021

VISTA Expression on Immune Cells Correlates With Favorable Prognosis in Patients With Triple-Negative Breast Cancer.

Front Oncol 2020 11;10:583966. Epub 2021 Jan 11.

Department of Breast Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of MedicalSciences, Beijing, China.

V-domain Ig suppressor of T-cell activation (VISTA), a newly discovered negative immune checkpoint, is thought to be related to immunotherapy resistance and may become a new immune therapeutic target. Here, we evaluated the expression of VISTA in a cohort containing 254 patients with untreated triple-negative breast cancer. The relevance of VISTA expression, clinicopathologic parameters, expression of other immune markers, and prognosis were investigated in the whole cohort. Genomic analysis of 139 triple-negative breast cancer (TNBC) patients from the cancer genome atlas (TCGA) was also performed. VISTA was expressed in the immune cells (ICs) and in the tumor cells (TCs) in 87.8% (223/254) and 18.5% (47/254) of the cohort, respectively. VISTA-positive ICs were associated with no lymph node metastasis (p < 0.001), American Joint Committee on Cancer (AJCC) stage I and II (p = 0.001) and basal-like subtype (p < 0.001). VISTA expression in ICs positively correlated with some tumor-infiltrating lymphocytes (TILs) types, particularly with the CD4TILs, which was consistent with mRNA level analysis from the TCGA database. Survival analysis showed that patients with VISTA-positive ICs had prolonged relapse-free and overall survival compared with the negative ones, especially among T1-2N0 stage patients. Multivariate analysis showed that it independently predicted the prognosis. These data confirmed the regulatory role of VISTA in anti-tumor immunity, changed our perception of VISTA as a negative immune checkpoint, and suggested VISTA as a potential therapeutic target for TNBC.
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http://dx.doi.org/10.3389/fonc.2020.583966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829913PMC
January 2021

Chemically Roughened, Sputtered Au Films with Trace-Loaded Manganese Oxide for both On-Chip and Off-Chip High Frequency Supercapacitors.

Nanomaterials (Basel) 2021 Jan 20;11(2). Epub 2021 Jan 20.

School of Metallurgy, Northeastern University, Shenyang 110819, Liaoning, China.

High frequency supercapacitors (HFSCs) are promising in alternating current line filtering and adaptable storage of high-frequency pulse electrical energy. Herein, we report a facile yet integrated-circuit-compatible fabrication of HFSC electrodes by combining chemical roughening of the sputtered metal (Au) films and in situ trace loading of a pseudocapacitive material (MnO). The developed electrode fabrication route is versatile for different substrates, and is described with the application paradigms of both on-chip (with Si/SiO substrate) and off-chip (without Si/SiO substrate, with Ti substrate as an example in this study) HFSCs. With Au/MnO films on Si/SiO substrates as the working electrodes, the derived on-chip HFSC displayed satisfactory performance in high frequency applications (i.e., an areal capacitance of 131.7 µF cm, a phase angle of -78°, and a RC time constant of 0.27 ms, at 120 Hz).
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http://dx.doi.org/10.3390/nano11020257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909291PMC
January 2021

Role and dynamics of vacuolar pH during cell-in-cell mediated death.

Cell Death Dis 2021 Jan 22;12(1):119. Epub 2021 Jan 22.

Laboratory of Cell Engineering, Institute of Biotechnology, Beijing, China.

The nonautonomous cell death by entosis was mediated by the so-called cell-in-cell structures, which were believed to kill the internalized cells by a mechanism dependent on acidified lysosomes. However, the precise values and roles of pH critical for the death of the internalized cells remained undetermined yet. We creatively employed keima, a fluorescent protein that displays different excitation spectra in responding to pH changes, to monitor the pH dynamics of the entotic vacuoles during cell-in-cell mediated death. We found that different cells varied in their basal intracellular pH, and the pH was relatively stable for entotic vacuoles containing live cells, but sharply dropped to a narrow range along with the inner cell death. In contrast, the lipidation of entotic vacuoles by LC3 displayed previously underappreciated complex patterns associated with entotic and apoptotic death, respectively. The pH decline seemed to play distinct roles in the two types of inner cell deaths, where apoptosis is preceded with moderate pH decline while a profound pH decline is likely to be determinate for entotic death. Whereas the cancer cells seemed to be lesser tolerant to acidified environments than noncancerous cells, manipulating vacuolar pH could effectively control inner cell fates and switch the ways whereby inner cell die. Together, this study demonstrated for the first time the pH dynamics of entotic vacuoles that dictate the fates of internalized cells, providing a rationale for tuning cellular pH as a potential way to treat cell-in-cell associated diseases such as cancer.
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http://dx.doi.org/10.1038/s41419-021-03396-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822940PMC
January 2021

Photoelectronic Properties of End-bonded InAsSb Nanowire Array Detector under Weak Light.

Nanoscale Res Lett 2021 Jan 21;16(1):13. Epub 2021 Jan 21.

State Key Laboratory of Infrared Physics, Shanghai Institute of Technical Physics Chinese Academy of Sciences, Shanghai, 200083, China.

A simple fabrication of end-bonded contacts InAsSb NW (nanowire) array detector to weak light is demonstrated in this study. The detector is fabricated using InAsSb NW array grown by molecular beam epitaxy on GaAs substrate. The metal-induced gap states are induced by the end-bonded contact which suppresses the dark current at various temperatures. The existence of the interface dipole due to the interfacial gap states enhances the light excitation around the local field and thus upgrades the photoresponsivity and photodetectivity to the weak light. The light intensity of the infrared light source in this report is 14 nW/cm which is about 3 to 4 orders of magnitude less than the laser source. The responsivity of the detector has reached 28.57 A/W at room temperature with the light (945 nm) radiation, while the detectivity is 4.81 × 10 cm·Hz W. Anomalous temperature-dependent performance emerges at the variable temperature experiments, and we discussed the detailed mechanism behind the nonlinear relationship between the photoresponse of the device and temperatures. Besides, the optoelectronic characteristics of the detector clarified that the light-trapping effect and photogating effect of the NWs can enhance the photoresponse to the weak light across ultraviolet to near-infrared. These results highlight the feasibility of the InAsSb NW array detector to the infrared weak light without a cooling system.
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http://dx.doi.org/10.1186/s11671-021-03476-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818373PMC
January 2021

Anomalous Photoelectrical Properties through Strain Engineering Based on a Single Bent InAsSb Nanowire.

ACS Appl Mater Interfaces 2021 Feb 20;13(4):5691-5698. Epub 2021 Jan 20.

State Key Laboratory of Infrared Physics, Shanghai Institute of Technical Physics, Chinese Academy of Sciences, Shanghai 200083, China.

In this study, electrical and photoresponse properties of bent InAsSb nanowires (NWs) were investigated to explore the impact of bending strain on the photoelectrical properties. The corresponding morphological and structural observations demonstrate the phase segregation and strain in the core-shell zinc-blende-structured InAsSb NWs. It is found that the device made of bent InAsSb individual NW presents the switch from negative photoconductivity (NPC) and positive photoconductivity (PPC). The transformation between NPC and PPC can be achieved by not only gate voltage but also bias voltage, indicating the potential in the pervasive computing of bent InAsSb NWs. This work combines the semiconductor properties, light excitation, and piezoelectric effect of the InAsSb NWs, providing new ideas for next-generation photoelectrical nanodevices.
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http://dx.doi.org/10.1021/acsami.0c16028DOI Listing
February 2021

The miR-204-5p/FOXC1/GDF7 axis regulates the osteogenic differentiation of human adipose-derived stem cells via the AKT and p38 signalling pathways.

Stem Cell Res Ther 2021 Jan 18;12(1):64. Epub 2021 Jan 18.

Department of Plastic Surgery, The First Hospital of China Medical University, NO 155 Nanjing street Heping Strict, Shenyang, 110001, Liaoning Province, China.

Background: Human adipose-derived stem cells (hADSCs) are stem cells with the potential to differentiate in multiple directions. miR-204-5p is expressed at low levels during the osteogenic differentiation of hADSCs, and its specific regulatory mechanism remains unclear. Here, we aimed to explore the function and possible molecular mechanism of miR-204-5p in the osteogenic differentiation of hADSCs.

Methods: The expression patterns of miR-204-5p, Runx2, alkaline phosphatase (ALP), osteocalcin (OCN), forkhead box C1 (FOXC1) and growth differentiation factor 7 (GDF7) in hADSCs during osteogenesis were detected by qRT-PCR. Then, ALP and alizarin red staining (ARS) were used to detect osteoblast activities and mineral deposition. Western blotting was conducted to confirm the protein levels. The regulatory relationship among miR-204-5p, FOXC1 and GDF7 was verified by dual-luciferase activity and chromatin immunoprecipitation (ChIP) assays.

Results: miR-204-5p expression was downregulated in hADSC osteogenesis, and overexpression of miR-204-5p suppressed osteogenic differentiation. Furthermore, the levels of FOXC1 and GDF7 were decreased in the miR-204-5p mimics group, which indicates that miR-204-5p overexpression suppresses the expression of FOXC1 and GDF7 by binding to their 3'-untranslated regions (UTRs). Overexpression of FOXC1 or GDF7 improved the inhibition of osteogenic differentiation of hADSCs induced by the miR-204-5p mimics. Moreover, FOXC1 was found to bind to the promoter of miR-204-5p and GDF7, promote the deacetylation of miR-204-5p and reduce the expression of miR-204-5p, thus promoting the expression of GDF7 during osteogenic differentiation. GDF7 induced hADSC osteogenesis differentiation by activating the AKT and P38 signalling pathways.

Conclusions: Our results demonstrated that the miR-204-5p/FOXC1/GDF7 axis regulates the osteogenic differentiation of hADSCs via the AKT and p38 signalling pathways. This study further revealed the regulatory mechanism of hADSC differentiation from the perspective of miRNA regulation.
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http://dx.doi.org/10.1186/s13287-020-02117-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814734PMC
January 2021

Long-term effectiveness of one-time endoscopic screening for esophageal cancer: A community-based study in rural China.

Cancer 2020 Oct 30;126(20):4511-4520. Epub 2020 Jul 30.

Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.

Background: Evidence is required to quantify the population-level effects of endoscopic screening for esophageal squamous cell carcinoma (ESCC). The objective of this study was to evaluate the long-term effectiveness of 1-time endoscopic ESCC screening in a Chinese rural population.

Methods: This community-based cohort study was based on an existing esophageal cancer screening program in Feicheng City, China. The screening group consisted of all permanent residents aged 40 to 69 years in 17 villages who were screened during 2006 through 2009, and the control group consisted of residents in another 43 villages who were not yet covered by the screening program. Residents in the remaining 511 villages were defined as the total population control. The cumulative incidence and mortality of ESCC and the observed and expected numbers of ESCC cases and deaths during the follow-up period (2010-2018) were calculated and compared.

Results: After a 9-year follow-up, the screening group (n = 8460) revealed reductions of 20% (relative risk, 0.80; 95% CI, 0.66-0.97) and 32% (relative risk, 0.68; 95% CI, 0.52-0.89) in ESCC cumulative incidence and mortality, respectively, compared with the control group (n = 20,468). Endoscopic screening prevented 0.41% of the population (attributable risk, 0.41%; 95% CI, 0.07%-0.75%) from ESCC occurrence and 0.38% (attributable risk, 0.38%; 95% CI, 0.14%-0.62%) from ESCC-related death. In the screening group, reductions of 43% (standardized incidence ratio, 0.57; 95% CI, 0.48-0.67) and 45% (standardized mortality ratio, 0.55; 95% CI, 0.44-0.69) were found in the observed cumulative cases and deaths, respectively, compared with the expected cases and deaths.

Conclusions: One-time endoscopic screening was associated with a significant and consistent reduction in ESCC incidence and mortality among individuals aged 40 to 69 years in high-risk areas.
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http://dx.doi.org/10.1002/cncr.33119DOI Listing
October 2020

Toxicological evaluation of transgenic silkworms.

Toxicol Res (Camb) 2020 Dec 18;9(6):845-853. Epub 2020 Dec 18.

State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400715, China.

Safety of transgenic silkworms must be evaluated before their commercial application. We assessed subacute toxicity using a 28-day feeding study in rats. Eighty rats were evenly allocated into four groups, with each group containing 10 male and 10 female rats. Rats of three groups were fed dried transgenic silkworm H19.9A pupae with overexpressed endogenous Bmhsp19.9, transgenic silkworm A4SOR pupae with overexpressed exogenous SOR, or normal silkworm pupae at a dose of 3.0 g/kg/day, respectively. The fourth group served as a normal feeding control. The body weight, feed consumption, hematology response variables, serum biochemical parameters, organ weights, gross necropsy, and histopathologic of animals were evaluated. No mortality, adverse effects, or major differences in the evaluated parameters were observed in the groups fed transgenic pupae in comparison with the control, suggesting that transgenic silkworms are toxicologically equivalent to normal silkworms and are safe for consumption in rats.
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http://dx.doi.org/10.1093/toxres/tfaa089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786172PMC
December 2020

Knockdown of circRNA_0007534 suppresses the tumorigenesis of cervical cancer via miR-206/GREM1 axis.

Cancer Cell Int 2021 Jan 14;21(1):54. Epub 2021 Jan 14.

Department of Pharmacology, Shandong Academy of Chinese Medicine, Jinan, Shandong, China.

Background: Increasing evidence manifested that circular RNAs (circRNAs) acted as crucial regulators in human cancers by targeting the miRNA/mRNA axis, including cervical cancer (CC). Circ_0007534 was reported to promote CC cell proliferation and invasion by the miR-498/BMI-1 axis. The aim of this study was to explore a novel miRNA/mRNA network underlying circ_0007534 in CC regulation.

Methods: The quantitative real-time polymerase chain reaction (qRT-PCR) was implemented to examine the levels of circ_0007534, miR-206 and Gremlin1 (GREM1). Cell viability was determined using MTT assay. BrdU and colony formation assays were performed for analyzing cell proliferation. Cell apoptosis was assessed by flow cytometry. The protein levels of GREM1 and apoptotic markers (Bcl-2, Bax, C-Caspase3) were measured via western blot. Cell invasion was detected by transwell assay. The target relationship was analyzed by dual-luciferase reporter assay. The impact of circ_0007534 on CC growth in vivo was ascertained by xenograft assay.

Results: Circ_0007534 expression was aberrantly increased in CC tissues and cells. Functionally, knockdown of circ_0007534 reduced CC cell growth and invasion but motivated apoptosis. In the mechanism, circ_0007534 targeted miR-206 and its regulatory function was associated with sponging miR-206. Moreover, circ_0007534 was found to regulate GREM1 level by targeting miR-206. The inhibitory effect of si-circ_0007534 on the malignant progression of CC was reversed after GREM1 was overexpressed. Furthermore, circ_0007534 inhibition also reduced tumor growth of CC in vivo partially by regulating miR-206/GREM1 axis.

Conclusion: These results suggested that knockdown of circ_0007534 promoted the level of miR-206 to induce the expression downregulation of GREM1, consequently inhibiting the progression of CC.
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http://dx.doi.org/10.1186/s12935-021-01749-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809877PMC
January 2021

Active Femtoliter Droplet Generation in Microfluidics by Confined Interface Vibration.

Langmuir 2021 Jan 11;37(3):1297-1305. Epub 2021 Jan 11.

College of Mechanical and Electronic Engineering, China University of Petroleum (East China), Qingdao 266580, China.

The precise and effective generation of micron-sized droplets is one of the most common and important issues for droplet-based microfluidics. Active droplet generation makes use of additional energy input in promoting interfacial instabilities for droplet generation. Here, we report a new technique for the active generation of femtoliter droplets in microfluidic systems using confined interfacial vibration (CIV). The CIV is formed at the orifice of a traditional inkjet nozzle first by pushing the liquid out and then pulling it back. Droplets are pinched off during the withdrawal process, and this is different from the current active droplet generation techniques, which only monodirectionally push the liquid out. Droplets with radius ranging from ca. 1 to 28 μm can be actively generated by CIV at an orifice with radius 30 μm, distinguishing from conventional active generation techniques in which the droplets are always comparable or slightly bigger than the orifice. Experimental results showed that the droplet volume can be customized by controlling the intensity of the CIV. The inherent digital nature of the inkjet technique enables easy and precise regulating of the droplet volume, making it seamlessly compatible with the digital microfluidic systems.
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http://dx.doi.org/10.1021/acs.langmuir.0c03368DOI Listing
January 2021