Publications by authors named "Sheng Zhao"

243 Publications

LncRNA TUG1 attenuates ischaemia-reperfusion-induced apoptosis of renal tubular epithelial cells by sponging miR-144-3p via targeting Nrf2.

J Cell Mol Med 2021 Sep 21. Epub 2021 Sep 21.

Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China.

Renal ischaemia/reperfusion (I/R) injury may induce kidney damage and dysfunction, in which oxidative stress and apoptosis play important roles. Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) are reported to be closely related to renal I/R, but the specific molecular mechanism is still unclear. The purpose of this research was to explore the regulatory effect of lncRNA TUG1 on oxidative stress and apoptosis in renal I/R injury. This research revealed that in renal I/R injury and hypoxia/reperfusion (H/R) injury in vitro, the expression level of lncRNA TUG1 was upregulated, and oxidative stress levels and apoptosis levels were negatively correlated with the expression level of lncRNA TUG1. Using bioinformatics databases such as TargetScan and microRNA.org, microRNA-144-3p (miR-144-3p) was predicted to be involved in the association between lncRNA TUG1 and Nrf2. This study confirmed that the level of miR-144-3p was significantly reduced following renal I/R injury and H/R injury in vitro, and miR-144-3p was determined to target Nrf2 and inhibit its expression. In addition, lncRNA TUG1 can reduce the inhibitory effect of miR-144-3p on Nrf2 by sponging miR-144-3p. In summary, our research shows that lncRNA TUG1 regulates oxidative stress and apoptosis during renal I/R injury through the miR-144-3p/Nrf2 axis, which may be a new treatment target for renal I/R injury.
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http://dx.doi.org/10.1111/jcmm.16924DOI Listing
September 2021

Exosomal miR-21 from tubular cells contributes to renal fibrosis by activating fibroblasts via targeting PTEN in obstructed kidneys.

Theranostics 2021 2;11(18):8660-8673. Epub 2021 Aug 2.

Department of Urology, Renmin Hospital of Wuhan University, Wuhan, 430060, China.

Ureteral obstruction-induced hydronephrosis is associated with renal fibrosis and progressive chronic kidney disease (CKD). Exosome-mediated cell-cell communication has been suggested to be involved in various diseases, including renal fibrosis. However, little is known regarding how exosomes regulate renal fibrosis in obstructed kidneys. We first examined the secretion of exosomes in UUO (unilateral ureteral obstruction) mouse kidneys and TGF-β1-stimulated tubular epithelial cells (NRK-52E). Exosomes from NRK-52E cells were subsequently harvested and incubated with fibroblasts (NRK-49F) or injected into UUO mice via the tail vein. We next constructed Rab27a knockout mice to further confirm the role of exosome-mediated epithelial-fibroblast communication relevant to renal fibrosis in UUO mice. High-throughput miRNA sequencing was performed to detect the miRNA profiles of TGFβ1-Exos. The roles of candidate miRNAs, their target genes and relevant pathways were predicted and assessed and by setting specific miRNA mimic, miRNA inhibitor, siRNA or miRNA LNA groups. Increased renal fibrosis was associated with prolonged UUO days, and the secretion of exosomes was markedly increased in UUO kidneys and TGF-β1-stimulated NRK-52E cells. Purified exosomes from TGF-β1-stimulated NRK-52E cells could activate fibroblasts and aggravate renal fibrosis and . In addition, the inhibition of exosome secretion by Rab27a knockout or GW4869 treatment abolished fibroblast activation and ameliorated renal fibrosis. Exosomal miR-21 was significantly increased in TGFβ1-Exos compared with Ctrl-Exos, and PTEN is a certain target of miR-21. The promotion or inhibition of epithelial exosomal miR-21 correspondingly accelerated or abolished fibroblast activation , and renal fibrosis after UUO was alleviated by miR-21-deficient exosomes through the PTEN/Akt pathway. Our findings reveal that exosomal miR-21 from tubular epithelial cells may accelerate the development of renal fibrosis by activating fibroblasts via the miR-21/PTEN/Akt pathway in obstructed kidneys.
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http://dx.doi.org/10.7150/thno.62820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419054PMC
August 2021

Two-staged posterior osteotomy surgery in complex and rigid congenital scoliosis in younger than 10 years old children.

BMC Musculoskelet Disord 2021 Sep 13;22(1):788. Epub 2021 Sep 13.

Department of Orthopedics, The Second Hospital of Shanxi Medical University, No. 382 Wuyi Road, Shanxi, 030001, Taiyuan, P.R. China.

Background: Congenital scoliosis caused by failure of multiply vertebral segmentation with concave fused rib or unsegmented bar combined with contralateralhemivertebra is usually rigid and produces enormous asymmetric growth. Fusionless techniques have less advantage and come with some complications. Paucity of data was reported for children with complex congenital scoliosis using two-staged osteotomy surgery.

Methods: From 2006 to 2016, 11 patients less than 10 years old undergoing two staged osteotomy surgery for complex rigid congenital scoliosis were retrospectively reviewed. The analysis included age at initial surgery, second surgery and at the latest follow-up, and complications. Changes in coronal major curve, thoracic kyphosis, lumbar lodorsis, apex vertebra translation, T1-T12 length, T1-S1 length, trunk shift, and SVAwere included in radiological evaluation.

Results: In all, the mean follow-up was 72.5 ± 23.8 (42 to 112) months. The mean flexibility of the spine was 17.4 and 17.8 % before two surgeries. The mean age at the initial surgery was 6.6 ± 2.6 (2.5-10) years. The mean fusion level was 4.6 ± 1.3 (2 to 6) segments. The mean scoliosis improved from 67.4° to 23.7° after initial surgery and was 17.4° at the latest follow-up. The average increase of T1-S1 length was 0.92 cm per year. No patients had neurological complications.

Conclusions: Two-staged osteotomy surgery including hemivertebrae resection or Y-shaped osteotomy can achieve good radiological and clinical outcomes without severe complications. This procedure can be an option of treatment for complex congenital scoliosis.
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http://dx.doi.org/10.1186/s12891-021-04682-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8439016PMC
September 2021

TRIB3 regulates FSHR expression in human granulosa cells under high levels of free fatty acids.

Reprod Biol Endocrinol 2021 Sep 9;19(1):139. Epub 2021 Sep 9.

Department of Gynecology and Obstetrics, Ruijin Hospital Affiliated with the Medical School of Shanghai Jiao Tong University, Shanghai, 200025, China.

Background: Granulosa cells (GCs) in cumulus oophorus highly express follicle stimulating hormone receptor (FSHR), which is the most important mediator of both estradiol synthesis and oocyte maturation. Obese women have elevated free fatty acids (FFAs) levels in their follicular fluids and decreased FSHR expression in GCs, which is related to an altered protein kinase B/glycogen synthase kinase 3β (Akt/GSK3β) signaling pathway. Such FFA increases accompany 3-fold rises in pseudokinase 3 (TRIB3) expression and reduce the Akt phosphorylation status in both the human liver and in insulinoma cell lines. Therefore, in a high FFA environment, we determined if TRIB3 mediates regulation of FSHR via the Akt/GSK3β signaling pathway in human GCs.

Methods: GCs from women undergoing in vitro fertilization were collected and designated as high and low FFAs cohorts based on their follicular fluid FFA content. GCs with low FFA levels and a human granulosa-like tumor (KGN) cell line were exposed to palmitic acid (PA), which is a dominate FFA follicular fluid constituent. The effects were assessed of this substitution on the Akt/GSK3β signaling pathway activity as well as the expressions of TRIB3 and FSHR at both the gene and protein levels by qPCR, Western blot and immunofluorescence staining analyses. Meanwhile, the individual effects of TRIB3 knockdown in KGN cells and p-AKT inhibitors were compared to determine the mechanisms of FFA-induced FSHR downregulation.

Results: The average FSH dose consuming per oocyte (FSH dose/oocyte) was elevated and Top embryo quality ratio was decreased in women with high levels of FFAs in their follicular fluid. In these women, the GC TRIB3 and ATF4 protein expression levels were upregulated which was accompanied by FSHR downregulation. Such upregulation was confirmed based on corresponding increases in their gene expression levels. On the other hand, the levels of p-Akt decreased while p-GSK3β increased in the GCs. Moreover, TRIB3 knockdown reversed declines in FSHR expression and estradiol (E2) production in KGN cells treated with PA, which also resulted in increased p-Akt levels and declines in the p-GSK3β level. In contrast, treatment of TRIB3-knockdown cells with an inhibitor of p-Akt (Ser473) resulted in rises in the levels of both p-GSK3β as well as FSHR expression whereas E2 synthesis fell.

Conclusions: During exposure to a high FFA content, TRIB3 can reduce FSHR expression through stimulation of the Akt/GSK3β pathway in human GCs. This response may contribute to inducing oocyte maturation.
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http://dx.doi.org/10.1186/s12958-021-00823-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428109PMC
September 2021

Construction of CoS2/Zn0.5Cd0.5S S-scheme heterojunction for enhancing H2 evolution activity under visible light.

Chemistry 2021 Aug 27. Epub 2021 Aug 27.

North Minzu University, School of Chemistry and Chemical Engineering, CHINA.

In the field of photocatalysis, building a heterojunction is an effective way to promote electron transfer and enhance the reducibility of electrons. Herein, the S-scheme heterojunction photocatalyst (CoS 2 /Zn 0.5 Cd 0.5 S) of CoS 2  nanospheres modified Zn 0.5 Cd 0.5 S solid solution was synthesized and studied. The H 2  evolution rate of composite catalyst reached 25.15 mmol·g -1 ·h -1 , which was 3.26 times that of single Zn 0.5 Cd 0.5 S, while pure CoS 2  showed almost no hydrogen production activity. Moreover, CoS 2 /Zn 0.5 Cd 0.5 S had excellent stability, and the hydrogen production rate after six cycles of experiments only dropped by 6.19%. In addition, photoluminescence spectroscopy and photoelectrochemical experiments had effectively proved that the photogenerated carrier transfer rate of CoS 2 /Zn 0.5 Cd 0.5 S was better than CoS 2  or Zn 0.5 Cd 0.5 S single catalyst. In this study, the synthesized CoS 2  and Zn 0.5 Cd 0.5 S were both n-type semiconductors. After close contact, they followed an S-scheme heterojunction electron transfer mechanism, which not only promoted the separation of their respective holes and electrons, but also retained a stronger reduction potential, thus promoting the reduction of H +  protons in photocatalytic experiments. In short, this work provided a new basis for the construction of S-scheme heterojunction in addition to being used for photocatalytic hydrogen production.
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http://dx.doi.org/10.1002/chem.202102811DOI Listing
August 2021

miR-132-3p promotes the cisplatin-induced apoptosis and inflammatory response of renal tubular epithelial cells by targeting SIRT1 via the NF-κB pathway.

Int Immunopharmacol 2021 Oct 30;99:108022. Epub 2021 Jul 30.

Department of Urology, Renmin Hospital of Wuhan University, Wuhan 430060, China. Electronic address:

Cisplatin is a highly effective and broad-spectrum anticancer drug for the clinical treatment of solid tumors. However, it causes acute kidney injury (AKI) in patients with cancer. Consequently, its clinical application is limited. The occurrence, development, and prognosis of AKI are closely associated with microRNA (miRNA), which needs validation as a biomarker, especially for the early stages of cisplatin-induced AKI. An example of miRNA is miR-132-3p, which plays important roles in inflammatory responses, cell proliferation, and apoptosis in a variety of diseases. However, variations in its expression, potential mechanisms, and downstream targets in cisplatin-induced AKI remain unclear. This study aimed to investigate the functions of miR-132-3p in cisplatin-induced AKI. Sequencing and qRT-PCR revealed that miR-132-3p was significantly upregulated in cisplatin-induced AKI models of mouse and human proximal renal tubular epithelial (HK-2) cells. Apoptosis and inflammatory responses were significantly suppressed by the inhibition of the miR-132-3p expression in cisplatin-stimulated HK-2 cells, and this suppression was blocked by miR-132-3p mimics. Bioinformatics and dual luciferase reporter gene assay identified the 3'- UTR of SIRT1 mRNA as a direct target of miR-132-3p. RNA-FISH and immunofluorescence co-localization demonstrated that miR-132-3p and SIRT1 directly combined and interacted in the cytoplasm of HK-2 cells. Mechanistically, the SIRT1 expression was suppressed and the NF-κB signaling pathway was activated by the upregulation of miR-132-3p in cisplatin-induced AKI. By contrast, the SIRT1 expression was upregulated after the inhibition of miR-132-3p. The ratios of p-p65/p65 and p-IκBα/IκBα were significantly reduced, and the expression levels of inflammatory biomarkers and apoptotic proteins induced by cisplatin were obviously attenuated. Our results suggested that miR-132-3p exacerbated cisplatin-induced AKI by negatively regulating SIRT1 and activating the NF-κB signaling pathway. Therefore, targeting miR-132-3p might be a potential adjuvant therapy for ameliorating AKI in cisplatin-treated patients.
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http://dx.doi.org/10.1016/j.intimp.2021.108022DOI Listing
October 2021

Identification and Validation of a Novel Immune-Related lncRNA Signature for Bladder Cancer.

Front Oncol 2021 12;11:704946. Epub 2021 Jul 12.

Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Purpose: We aimed to construct an immune-related long noncoding ribonucleic acids (irlncRNA) signature to evaluate the prognosis of patients without specific expression level of these irlncRNA.

Methods: The raw transcriptome data were downloaded from The Cancer Genome Atlas (TCGA), irlncRNAs were filtered out using an online immune related gene database and coexpression analysis, differently expressed irlncRNA (DEirlncRNA) pairs were identified by univariate analysis. The areas under curve (AUC) were compared and the Akaike information criterion (AIC) values of receiver operating curve (ROC) was counted, the most optimal model was constructed to divide bladder cancer patients into high- and low-risk groups usingõ the cut-off point of ROC. Then, we evaluated them from multiple perspectives, such as survival time, clinic-pathological characteristics, immune-related cells infiltrating, chemotherapeutics efficacy and immune checkpoint inhibitors.

Results: 14 DEirlncRNA pairs were included in this signature. Patients in high-risk groups demonstrated apparent shorter survival time, more aggressive clinic-pathological characteristics, different immune-related cells infiltrating status, lower chemotherapeutics efficacy.

Conclusion: The irlncRNA signature demonstrated a promising prediction value for bladder cancer patients and was important in guiding clinical treatment.
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http://dx.doi.org/10.3389/fonc.2021.704946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311739PMC
July 2021

High-quality genome assembly of Huazhan and Tianfeng, the parents of an elite rice hybrid Tian-you-hua-zhan.

Sci China Life Sci 2021 Jun 28. Epub 2021 Jun 28.

Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Genome Analysis Laboratory of the Ministry of Agriculture, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, 518120, China.

High-quality rice reference genomes have accelerated the comprehensive identification of genome-wide variations and research on functional genomics and breeding. Tian-you-hua-zhan has been a leading hybrid in China over the past decade. Here, de novo genome assembly strategy optimization for the rice indica lines Huazhan (HZ) and Tianfeng (TF), including sequencing platforms, assembly pipelines and sequence depth, was carried out. The PacBio and Nanopore platforms for long-read sequencing were utilized, with the Canu, wtdbg2, SMARTdenovo, Flye, Canu-wtdbg2, Canu-SMARTdenovo and Canu-Flye assemblers. The combination of PacBio and Canu was optimal, considering the contig N50 length, contig number, assembled genome size and polishing process. The assembled contigs were scaffolded with Hi-C data, resulting in two "golden quality" rice reference genomes, and evaluated using the scaffold N50, BUSCO, and LTR assembly index. Furthermore, 42,625 and 41,815 non-transposable element genes were annotated for HZ and TF, respectively. Based on our assembly of HZ and TF, as well as Zhenshan97, Minghui63, Shuhui498 and 9311, comprehensive variations were identified using Nipponbare as a reference. The de novo assembly strategy for rice we optimized and the "golden quality" rice genomes we produced for HZ and TF will benefit rice genomics and breeding research, especially with respect to uncovering the genomic basis of the elite traits of HZ and TF.
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http://dx.doi.org/10.1007/s11427-020-1940-9DOI Listing
June 2021

Reference ranges of fetal heart function using a Modified Myocardial Performance Index: a prospective multicentre, cross-sectional study.

BMJ Open 2021 07 7;11(7):e049640. Epub 2021 Jul 7.

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

Objectives: The primary aim of this study was to establish the normal reference ranges of the fetal left ventricular (LV) Modified Myocardial Performance Index (Mod-MPI). A secondary aim was to evaluate the agreement between manual and automatic measurements for fetal Mod-MPI.

Design: A prospective, multicentre, cross-sectional study.

Participants: Normal singleton pregnancies.

Methods: The LV functions of normal singleton pregnancies were assessed in nine centres covering eight provinces in China using unified ultrasound protocols and settings and standardised measurements by pulsed Doppler at 20-24, 28-32 and 34-38 weeks of gestation. The isovolumetric relaxation time (IRT), isovolumetric contraction time, ejection time (ET) and Mod-MPI were measured both automatically and manually.

Results: This cross-sectional study included 2081 fetuses, and there was a linear correlation between gestational age (GA) and Mod-MPI (0.416+0.001×GA (weeks), p<0.001, r=0.013), IRT (36.201+0.162× GA (weeks), p<0.001, r=0.021) and ET (171.418-0.078*GA (weeks), p<0.001, r=0.002). This finding was verified using longitudinal data in a subgroup of 610 women. The agreement between the manual and automated measurements for Mod-MPI was good.

Conclusions: We constructed normal reference values of fetal LV Mod-MPI. Automatic measurement can be considered for ease of measurement in view of the good agreement between the automatic and manual values.
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http://dx.doi.org/10.1136/bmjopen-2021-049640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264880PMC
July 2021

Factors Associated With Mental Health Symptoms During the COVID-19 Pandemic in Hong Kong.

Front Psychiatry 2021 7;12:617397. Epub 2021 Jun 7.

School of Public Health, University of Hong Kong, Hong Kong, China.

The COVID-19 pandemic has led to an increasing mental health burden. We examined the factors associated with mental health symptoms in Chinese general adults in Hong Kong. We conducted a dual-frame (landline and mobile) survey on Chinese adults aged 18 years or older in April 2020. Shortage of preventive materials, perceptions of the outbreak (each item range 1-5), and reduction in income were assessed. Mental health symptoms measured included stress (Perceived Stress Scale-4, range 0-16), anxiety (General Anxiety Disorders-2, range 0-6, cutoff >2), and depressive symptoms (Patient Health Questionnaire-2, range 0-6, cutoff >2). Results were weighted by the general population distribution. Associations were analyzed by multivariable linear (for stress) and logistic (for anxiety and depressive symptoms) regression adjusting for sociodemographic and health-related covariates, including confirmed or in close contacts of confirmed cases, chronic disease, self-rated health, and smoking and alcohol drinking behavior. Of the 1,501 participants (52.5% female, 55.0 aged 30-59 years), the average stress score was 7.20 (SD 2.12). 218 (15.8%) and 206 (14.8%) participants had anxiety and depressive symptoms, respectively. Shortage in facemasks (20.8%), alcohol-based hand sanitizers (13.9%), and cleaning products (7.3%) was reported. Participants generally disagree with the perception of at risk of getting infected in the coming 6 months (mean 2.2, SD 1.1), but tended to agree with the perception of worry that the people around pose a threat to them (mean 3.6, SD 0.9) and the outbreak has greatly affected their daily life (mean 3.7, SD 0.9). 59.3% employed participants had income reduction and 6.2% had become unemployed since the outbreak. Stress, anxiety, and depressive symptoms were more prevalent in those with shortages of preventive materials and negative perceptions of the outbreak (all < 0.05). Reduction in income and unemployment were associated with more mental health symptoms (all < 0.05). Shortage of preventive materials, negative perceptions, financial loss, and unemployment were prevalent during the outbreak and found in association with higher stress and more anxiety and depressive symptoms. Further research and urgent actions are warranted to relieve stress and promote mental health, targeting the many risk factors identified by our study.
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http://dx.doi.org/10.3389/fpsyt.2021.617397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215194PMC
June 2021

Associations of COVID-19 online information sources and information overload with psychological distress symptoms: a population-based study.

Transl Behav Med 2021 07;11(7):1330-1338

School of Nursing, University of Hong Kong, Hong Kong, China.

Using information communication technologies as information sources of COVID-19 was associated with psychological problems, but mechanisms remain uncertain. We examined associations of COVID-19 information sources and information overload with psychological distress symptoms and explored the mediating effect of information overload in Hong Kong. A random sample of Chinese adults (N = 1501; 52.6% females; 55.0% aged 30-59) from dual landline and online surveys in April 2020 reported frequency of using traditional media, internet websites, social networking sites, instant messaging, and online discussion forums as COVID-19 information sources. Psychological distress symptoms were measured using the Patient Health Questionnaire 4-item ([PHQ-4]; 0-12). Information overload defined as a perception of being overwhelmed was measured (1-6). Linear regressions were performed to analyze the associations, and the mediating effect of information overload was examined. Greater PHQ-4 score was observed for frequent use of internet websites (adjusted b = 0.58, 95% CI 0.29, 0.87, adjusted β = 0.12) and online discussion forums (adjusted b = 0.39, 95% CI 0.08, 0.70, adjusted β = 0.08) and information overload (adjusted b = 0.54, 95% CI 0.44, 0.63, adjusted β = 0.28). Information overload mediated 44.9% and 36.9% of associations of frequent use of internet websites and online discussion forums with PHQ-4 score, respectively. Frequent use of social networking sites was associated with lower PHQ-4 score (adjusted b = -0.37, 95% CI -0.69, -0.04, adjusted β = -0.07) partially through lower information overload (37.5%). Psychological distress symptoms were associated with frequent use of internet websites and online discussion forums as COVID-19 information sources, which were mediated through information overload.
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http://dx.doi.org/10.1093/tbm/ibab086DOI Listing
July 2021

Efficacy of curcumin for wound repair in diabetic rats/mice: a systematic review and meta-analysis of preclinical studies.

Curr Pharm Des 2021 Jun 17. Epub 2021 Jun 17.

Department of Burn, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.

Background: Curcumin possesses multiple bioactivities that have beneficial effects on diabetic foot ulcers. Herein, we aimed to conduct a systematic preclinical review of 9 studies including a total of 262 animals, to assess the possible mechanisms of curcumin for wound healing in diabetic animals.

Methods: Five databases were searched from inception to May 12, 2020; Rev-Man 5.3 software was applied for data analyses. Cochrane Collaboration's tool 10-item checklist was used to evaluate the methodological quality, and data revealed scores of risk of bias ranging from 2 to 5.

Results: Meta-analysis indicated that curcumin had significant effects on wound healing rate and blood vessel density when compared with control (P < 0.05). The wound regeneration properties of curcumin for diabetic wounds are thought to mainly work through the possible mechanisms of antioxidation, enhanced cell proliferation, increased collagen formation, and angiogenesis. However, the anti-inflammatory effect on wounds in diabetic animals remains controversial.

Conclusions: The findings indicate that more randomized controlled trials should be pursued to obtain more reliable results regarding inflammatory response. Overall, curcumin might be a probable candidate for diabetic foot ulcers and may contribute to future clinical trials.
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http://dx.doi.org/10.2174/1381612827666210617122026DOI Listing
June 2021

Design of nanozymes for inflammatory bowel disease therapy.

Sci China Life Sci 2021 Aug 8;64(8):1368-1371. Epub 2021 Jun 8.

Department of Biomedical Engineering, College of Engineering and Applied Sciences, Nanjing National Laboratory of Microstructures, Jiangsu Key Laboratory of Artificial Functional Materials, Nanjing University, Nanjing, 210023, China.

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http://dx.doi.org/10.1007/s11427-020-1937-6DOI Listing
August 2021

A radiomics-based nomogram for preoperative T staging prediction of rectal cancer.

Abdom Radiol (NY) 2021 10 3;46(10):4525-4535. Epub 2021 Jun 3.

Department of Interventional Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.

Purpose: To investigate the value of a radiomics-based nomogram in predicting preoperative T staging of rectal cancer.

Methods: A total of 268 eligible rectal cancer patients from August 2012 to December 2018 were enrolled and allocated into two datasets: training (n = 188) and validation datasets (n = 80). Another set of 32 patients from January 2019 to July 2019 was included in a prospective analysis. Pretreatment T2-weighted images were used to radiomics features extraction. Feature selection and radiomics score (Rad-score) construction were performed through a least absolute shrinkage and selection operator regression analysis. The nomogram, which included Rad-scores and clinical factors, was built using multivariate logistic regression. Discrimination, calibration, and clinical utility were used to evaluate the performance of the nomogram.

Results: The Rad-score containing nine selected features was significantly related to T staging. Patients who had locally advanced rectal cancer (LARC) generally had higher Rad-scores than patients with early-stage rectal cancer. The nomogram incorporated Rad-scores and carcinoembryonic antigen levels and showed good discrimination, with an area under the curve (AUC) of 0.882 (95% confidence interval [CI] 0.835-0.930) in the training dataset and 0.846 (95% CI 0.757-0.936) in the validation dataset. The calibration curves confirmed high goodness of fit, and the decision curve analysis revealed the clinical value. A prospective analysis demonstrated that the AUC of the nomogram to predict LARC was 0.859 (95% CI 0.730-0.987).

Conclusion: A radiomics-based nomogram is a novel method for predicting LARC and can provide support in clinical decision making.
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http://dx.doi.org/10.1007/s00261-021-03137-1DOI Listing
October 2021

Baicalin Inhibits NLRP3 Inflammasome Activity Via the AMPK Signaling Pathway to Alleviate Cerebral Ischemia-Reperfusion Injury.

Inflammation 2021 Oct 2;44(5):2091-2105. Epub 2021 Jun 2.

Department of Pharmacy, College of Medical, Wuhan University of Science and Technology, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan, 430065, Hubei Province, China.

Baicalin has been reported to have ameliorative effects on nerve-induced hypoxic ischemia injury; however, its role in the NLRP3 inflammasome-dependent inflammatory response during cerebral ischemia-reperfusion remains unclear. To investigate the molecular mechanisms involved in baicalin alleviating cerebral ischemia-reperfusion injury, we investigated the AMPK signaling pathway which regulates NLRP3 inflammasome activity. SD rats were treated with baicalin at doses of 100 mg/kg and 200 mg/kg, respectively, after middle cerebral artery occlusion at 2 h and reperfusion for 24 h (MCAO/R). MCAO/R treatment significantly increased cerebral infarct volume, changed the ultrastructure of nerve cells, and activated the NLRP3 inflammasome, manifesting as significantly increased expression of NLRP3, ASC, cleaved caspase-1, IL-1β, and IL-18. Our results demonstrated that baicalin treatment effectively reversed these phenomena in a dose-dependent manner. Additionally, inhibition of NLRP3 expression was found to promote the neuroprotective effects of baicalin on cortical neurons. Furthermore, baicalin remarkably increased the expression of p-AMPK following oxygen glucose deprivation/reperfusion (OGD/R). The expression of the NLRP3 inflammasome was also increased when the AMPK pathway was blocked by compound C. Taken together, our findings reveal that baicalin reduces the activity of the NLRP3 inflammasome and consequently inhibits cerebral ischemia-reperfusion injury through activation of the AMPK signaling pathway.
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http://dx.doi.org/10.1007/s10753-021-01486-zDOI Listing
October 2021

The VANGL1 P384R variant cause both neural tube defect and Klippel-Feil syndrome.

Mol Genet Genomic Med 2021 Jul 20;9(7):e1710. Epub 2021 May 20.

Department of Ultrasound Diagnosis, Maternal and Child Health Hospital of Hubei Province, Wuhan, China.

Background: Neural tube defect (NTD) is a common birth defect causing much death in the world. Variants in VANGL1 lead to NTD and caudal regression syndrome. NTD displays a complex phenotype encompassing both genetic and environmental factors.

Methods: The fetus was diagnosed by prenatal ultrasound examination. Postnatal CT and autopsy were performed. Genetic testing was conducted in the family and Sanger sequencing was validated. Multiple prediction soft-wares were used to predict the pathogenicity of the variant.

Results: The VANGL1 gene variant c.1151C>G (P384R) was detected in a fetus diagnosed with tethered spinal cord and sacrococcygeal lipoma. The VANGL1 variant c.1151C>G (P384R) was reported in a Klippel-Feil syndrome patient. The VANGL1 variant was validated in the trio-family but the mother showed no abnormalities.

Conclusion: Overall, this study presents fetal NTD caused by the same VANGL1 variant found in a Klippel-Feil syndrome patient with complete clinical information of prenatal ultrasound, postnatal CT, and genetic results as early as 25 GW. Our study not only expands the VANGL1 mutational spectrum but also sheds light on the important role of the VANGL1 P384R variant in human development.
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http://dx.doi.org/10.1002/mgg3.1710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8372072PMC
July 2021

Mobile chat-based support plus nicotine replacement therapy sampling to promote smoking cessation for community smokers: A randomized controlled trial.

Tob Induc Dis 2021 27;19:32. Epub 2021 Apr 27.

School of Nursing, The University of Hong Kong, Hong Kong.

Introduction: Mobile instant messaging could deliver real-time, personalized, interactive smoking cessation support. Nicotine replacement therapy (NRT) is effective in increasing quit attempts and abstinence but is underused. We assessed the feasibility of mobile chat-based intervention combined NRT sampling (NRT-S) on abstinence.

Methods: In this two-arm, single-blinded, randomized controlled trial, adult (≥18 years) daily cigarette smokers were proactively recruited from Hong Kong community settings using 'foot-in-the-door' approach during December 2017 to March 2018. All participants received brief advice on quitting, 1-week of NRT-S, active referral to smoking cessation services, and were individually randomized (1:1) at baseline. The intervention group received two months of chat-based support via instant messaging. The control group received general smoking cessation text messages. The primary outcome was smoking abstinence validated by exhaled carbon monoxide (<4 ppm) and salivary cotinine (<10 ng/mL) at 3 and 6 months using intention-to-treat analysis.

Results: A total of 119 participants (80.7% male, 60.5% aged 30-40 years) were randomized and analyzed. Among the 14 and 13 self-reported quitters at 3 and 6 months respectively, only 3 and 1 had biochemical validation. The 3 months validated abstinence rate was 2/62 (intervention) vs 1/57 (control) (AOR=1.07; 95% CI: 0.08-13.65). At 6 months follow-up (68.9% of participants retained), more participants in the intervention group reported quitting (10/62 vs 3/57; AOR=2.83; 95% CI: 0.70-11.30), smoking reduction (20/62 vs 11/57; AOR=1.74; 95% CI: 0.71-4.26), and quit attempts (56/62 vs 44/57; AOR=2.61; 95% CI: 0.88-7.82). Significantly more NRT-S use (39/62 vs 22/57; AOR=2.27; 95% CI: 1.04-4.96) was observed in the intervention group. Participants engaged in mobile chat support (21/62) reported more NRT-S use (76.2% vs 56.1%), although not statistically significant.

Conclusions: Mobile chat-based support plus NRT-S was feasible and showed preliminary evidence of increased quitting, smoking reduction, quit attempts, and NRT-S use in proactively recruited community smokers.

Trial Registration: ClinicalTrials.gov: NCT03574077.
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http://dx.doi.org/10.18332/tid/133373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078100PMC
April 2021

Long-term results after the one-stage posterior-only surgical correction of thoraco-lumbar kyphoscoliosis in congenital spine deformity caused by two ipsilateral hemi-vertebrae.

BMC Musculoskelet Disord 2021 Apr 2;22(1):327. Epub 2021 Apr 2.

Department of Orthopedics, The Second Hospital of Shanxi Medical University, No. 382 Wuyi Road, Taiyuan, Shanxi, 030001, People's Republic of China.

Background: Two ipsilateral hemivertebrae is less common and presents severe growth imbalance caused by the vertebral anomalies. However, there is a paucity of reports regarding to two ipsilateral thoracolumbar hemivertebrae. The purpose of present study is to evaluate the long-term outcomes of the posterior surgical correction of thoraco-lumbar spine deformity caused by two ipsilateral hemivertebrae.

Methods: From 2006 to 2014, a total of 14 consecutive pediatric patients with congenital thoraco-lumbar hemivertebrae were treated by posterior excision of hemivertebrae with short segment fusion. The following parameters were measured: coronal major curvature, cranial and caudal compensatory curvature, segmental kyphosis, lumbar lordosis, trunk shift, apical vertebra translation and sagittal vertical axis. These results were compared and evaluated in preoperatively, immediately postoperatively and at the final follow-up. All patients had a minimum of 5 years follow-up.

Results: The mean age at surgery was 11.1 ± 4.8 years (2yos to 17yos). The mean follow-up period was 80.2 ± 19.4 months (60mons to 117mons). There was a mean improvement of 74.2% in the coronal major curve from a mean angle of 64.1° before surgery to 15.8° at the final follow-up. The cranial and caudal curves improved of 69.8 and 69.0% from 25.6° to 7.7°, 26.9 to 8.2, respectively. The mean thoraco-lumbar kyphosis was 59.9° before and 13.6° after surgery, 20.8° at the final follow-up. Alignment in the coronal and sagittal plane was either maintained or improved within normal values in all patients.

Conclusions: Good correction and spinal balance can be achieved by posterior-only hemivertebrectomy in patients with thoracolumbar kyphocsoliosis caused by two ipsilateral hemivertebra. The complication of neurological injury is low but a technically demanding procedure. More attention should be paid in residual curve progression after surgery.
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http://dx.doi.org/10.1186/s12891-021-04201-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019164PMC
April 2021

Socioeconomic Disparities in eHealth Literacy and Preventive Behaviors During the COVID-19 Pandemic in Hong Kong: Cross-sectional Study.

J Med Internet Res 2021 04 14;23(4):e24577. Epub 2021 Apr 14.

School of Nursing, University of Hong Kong, Hong Kong, China (Hong Kong).

Background: eHealth literacy can potentially facilitate web-based information seeking and taking informed measures.

Objective: This study aimed to evaluate socioeconomic disparities in eHealth literacy and seeking of web-based information on COVID-19, and their associations with COVID-19 preventive behaviors.

Methods: The COVID-19 Health Information Survey (CoVHIns), using telephonic (n=500) and web-based surveys (n=1001), was conducted among adults in Hong Kong in April 2020. The Chinese eHealth literacy scale (eHEALS; score range 8-40) was used to measure eHealth literacy. COVID-19 preventive behaviors included wearing surgical masks, wearing fabric masks, washing hands, social distancing, and adding water or bleach to the household drainage system. Adjusted beta coefficients and the slope indices of inequality for the eHEALS score by socioeconomic status, adjusted odds ratios (aORs) for seeking of web-based information on COVID-19 by socioeconomic status, and aORs for the high adherence to preventive behaviors by the eHEALS score and seeking of web-based information on COVID-19 were calculated.

Results: The mean eHEALS score was 26.10 (SD 7.70). Age was inversely associated with the eHEALS score, but education and personal income were positively associated with the eHEALS score and seeking of web-based information on COVID-19 (for all, P for trend<.05). Participants who sought web-based information on COVID-19 showed high adherence to the practice of wearing surgical masks (aOR 1.56, 95% CI 1.15-2.13), washing hands (aOR 1.33, 95% CI 1.05-1.71), social distancing (aOR 1.48, 95% CI 1.14-1.93), and adding water or bleach to the household drainage system (aOR 1.67, 95% CI 1.28-2.18). Those with the highest eHEALS score displayed high adherence to the practice of wearing surgical masks (aOR 3.84, 95% CI 1.63-9.05), washing hands (aOR 4.14, 95% CI 2.46-6.96), social distancing (aOR 2.25, 95% CI 1.39-3.65), and adding water or bleach to the household drainage system (aOR 1.94, 95% CI 1.19-3.16), compared to those with the lowest eHEALS score.

Conclusions: Chinese adults with a higher socioeconomic status had higher eHealth literacy and sought more web-based information on COVID-19; both these factors were associated with a high adherence to the guidelines for preventive behaviors during the COVID-19 pandemic.
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http://dx.doi.org/10.2196/24577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048711PMC
April 2021

Association of Mobile Instant Messaging Chat Group Participation With Family Functioning and Well-Being: Population-Based Cross-sectional Study.

J Med Internet Res 2021 03 15;23(3):e18876. Epub 2021 Mar 15.

School of Public Health, The University of Hong Kong, Hong Kong, China (Hong Kong).

Background: Convenient and quality family communication improves family functioning and well-being. Using mobile instant messaging (IM) for family communication is increasingly popular, but its association with family functioning and family well-being has not been reported.

Objective: The aim of this study was to examine the association of the use of family IM chat groups with family functioning and well-being, and the mediating effect of family communication quality among Chinese adults in Hong Kong.

Methods: We analyzed data from the Family and Health Information Trend Survey (FHInTS), a territory-wide, probability-based telephone survey conducted in 2017. The quality of family communication, family functioning, and well-being was assessed using the Family Communication Scale; Family Adaptation, Partnership, Growth, Affection, and Resolve (APGAR) Scale; and Family Well-Being Scale (family heath, harmony, and happiness), respectively. Respondents also reported the number of family IM chat groups (0, 1, 2, ≥3), and numbers of IM messages received (<1, 1-2, 3-10, 11-20, >20) and sent (<1, 1-2, 3-10, 11-20, >20) daily. The frequency of family IM chat interaction (range 0-8) was calculated by combining the number of messages received from and sent to the family IM chat groups daily. Covariates included sociodemographic characteristics and the frequency of family face-to-face communication (often, sometimes, seldom, or never). Data were weighted by sex, age, and education of the general population. Adjusted β coefficients of family functioning and well-being in relation to having a family IM chat group, and numbers of messages received and sent were calculated. The mediation effects of family communication on these associations were assessed, controlling for the covariates.

Results: A random sample of 1638 Chinese adults (45.6% men; 78.1% aged 25 to 64 years) were interviewed (response rate: 74.4%). Female, younger age, being married or cohabiting, higher education, higher income, better family functioning, and well-being were associated with having at least one family IM chat group (all P<.01). Higher scores of family communication, family APGAR, and family well-being were associated with having more family IM chat groups and more messages received from and sent to family IM chat groups daily (all P for trend <.01). More frequent family IM chat interaction was associated with higher scores of family communication, family APGAR, and family well-being (β=.16-.83, all P for trend <.001). The associations of family IM chat interaction with family functioning and well-being were moderately (51.0%-59.6%) mediated by family communication.

Conclusions: Use of a family IM chat group was associated with higher family functioning and well-being, and the association was partially mediated by family communication.
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http://dx.doi.org/10.2196/18876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074847PMC
March 2021

Schizandrin B attenuates hypoxia/reoxygenation injury in H9c2 cells by activating the AMPK/Nrf2 signaling pathway.

Exp Ther Med 2021 Mar 18;21(3):220. Epub 2021 Jan 18.

Department of Cardiology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, P.R. China.

Schizandrin B exhibits prominent antioxidant and anti-inflammatory effects, and plays an important role in ameliorating myocardial ischemia/reperfusion injury. However, the underlying protective mechanisms remain to be elucidated. The aim of the present study was to explore the cardioprotective effects of schizandrin B against hypoxia/reoxygenation (H/R)-induced H9c2 cell injury, focusing on the role of the adenosine monophosphate-activated protein kinase (AMPK)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in this process. The results showed that schizandrin B attenuated the H/R-induced decrease in cell viability and the increase in lactate dehydrogenase release, as well as the apoptosis rate in H9c2 cells. Schizandrin B also mitigated H/R-induced oxidative stress, as illustrated by the decrease in intracellular reactive oxygen species generation, malondialdehyde content and NADPH oxidase 2 expression, and the increase in antioxidant enzyme superoxide dismutase and glutathione peroxidase activities. In addition, schizandrin B reversed the H/R-induced upregulation of pro-inflammatory cytokines [interleukin (IL)-1β (IL-1β) tumor necrosis factor-α, IL-6 and IL-8] and the downregulation of anti-inflammatory cytokines (transforming growth factor-β and IL-10) in the culture supernatant. Notably, schizandrin B increased the expression of Nrf2, NAD(P)H: Quinone oxidoreductase (NQO-1) and heme oxygenase-1 (HO-1) in H/R-treated H9c2 cells, activating the Nrf2 signaling pathway. The cardioprotection of schizandrin B against H/R injury was inhibited by Nrf2 knockdown induced byNrf-2-specific small interfering RNA (siRNA; si-Nrf2) transfection. Furthermore, schizandrin B enhanced phosphorylated (p)-AMPK expression, while AMPK knockdown induced by AMPK-specific siRNA(si-AMPK) transfection remarkably eliminated schizandrin B-induced cardioprotection and reduced Nrf2 expression in H/R-treated H9c2 cells. Taken together, these results suggested that schizandrin B exerts cardioprotection on H/R injury in H9c2 cells due to its antioxidant and anti-inflammatory activities via activation of the AMPK/Nrf2 pathway.
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http://dx.doi.org/10.3892/etm.2021.9651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851604PMC
March 2021

Dynamic data reconciliation to improve the result of controller performance assessment based on GMVC.

ISA Trans 2021 Nov 28;117:288-302. Epub 2021 Jan 28.

National-Local Joint Engineering Laboratory for Digitalize Electrical Design Technology, Wenzhou University, Wenzhou 325035, China.

Due to the complexity of the industrial working environment, controllers are susceptible to various disturbance signals, resulting in unsatisfactory control performance. Therefore, it is especially important to assess the controller performance. Considering the harmful effect of measurement noise on controller performance assessment (CPA) based on generalized minimum variance control (GMVC), this paper proposes dynamic data reconciliation (DDR) to improve the accuracy of CPA based on GMVC. The paper first introduces CPA based on GMVC, and then analyzes the influence of measurement noise on GMVC based CPA index. DDR combined with GMVC based CPA is then proposed and analyzed in both SISO and MIMO systems to weaken the impact of measurement noise on CPA index. For both Gaussian distributed noise and non-Gaussian distributed noise, the formulation of DDR is derived from the Bayesian formula and maximum likelihood estimate. The effectiveness of the proposed method is verified in different case studies (involving both SISO and MIMO systems), and further verified by the control process of DC-AC converter. The simulation and experiment results demonstrate that the results of CPA based on GMVC can be obviously improved by using DDR.
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http://dx.doi.org/10.1016/j.isatra.2021.01.047DOI Listing
November 2021

Role of shear wave elastography measured in the flaccid state in predicting arteriogenic erectile dysfunction.

Andrologia 2021 May 1;53(4):e13996. Epub 2021 Feb 1.

The Department of Urology, The First Affiliated Hospital of Anhui Medical University, Anhui Province, China.

The gold-standard method for diagnosing arteriogenic erectile dysfunction (AED) is the penile Doppler ultrasonography. We proposed a novel method for predicting AED using ultrasonic shear wave elastography (SWE) considering that the former was invasive and variable. A total of 98 male patients were enrolled in our study, referred for ED between December 2018 and October 2020. For comparison, we also included 42 volunteers from the Healthy Physical Examination Center of our hospital. The Penile Doppler Ultrasonography (PDU) and SWE were performed for all patients with the intracavernosal injection (ICI). We named three groups as AED group, nonvascular ED group and healthy controls group. No statistically significant differences were found among the three groups in terms of demographic and clinical characteristics. There were no significant differences in IIEF-5 between AED and nonvascular ED. A significant (r = 0.642, p < 0.0001) positive correlation between flaccid and erectile SWE was observed. With a cut-off value of 13.45 KPa, the area under curve, specificity, and sensitivity of the SWE values under the flaccid state in distinguishing AED from healthy subjects were 0.867, 0.786 and 0.896 respectively. The SWE value in the flaccid state can distinguish the AED from healthy subjects.
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http://dx.doi.org/10.1111/and.13996DOI Listing
May 2021

Preliminary assessment of genotoxic effects induced by radiation from EAST usingmicronucleus assay.

J Radiol Prot 2021 Jan 28. Epub 2021 Jan 28.

Chinese Academy of Sciences Institute of Plasma Physics, Hefei, Anhui, CHINA.

During long-pulse deuterium plasma operating in Experimental Advanced Superconducting Tokamak (EAST), a mixed radiation field will be generated, which is mainly composed of fusion neutrons, gamma rays, x-rays and so on. More accurately and effectively dose monitoring methods were developed and established to obtain the ionizing radiation intensity for the stable operation of the device and personnel radiation safety. As we know, there is few reports about the biological effects of radiation induced by fusion neutrons and γ radiation, which is of vital importance to the assessing radiation hazards from fusion devices such as EAST on human being and ecological environment. In present study, three positions in EAST hall were selected to detect genotoxic effects induced by nuclear fusion radiation using Vicia faba micronucleus test for the first time. The doses of neutrons and gamma rays at these places were measured by thermoluminescence dosimeters for four times from June 2019 to May 2020. The radiation doses were decreased as the distances from EAST device shell gradually increased from S1 to S3. Radiation in EAST hall resulted in a significant induction of micronucleus in Vicia faba root tips cells compared to negative control, which was different from micronucleus frequency indued by fission neutrons, γ-rays and other kind of radiation in previous studies. These results indicated that there has existence of potential genotoxic effects induced by radiation from EAST which was different from other radiation and suggested that it was not allowed to enter the experimental hall during the discharge process, and the radiation protection measures should be taken during the necessary maintenance to avoid radiation damage. These newly acquired results will certainly increase our knowledge on the biological effects induced by radiation from nuclear fusion and provide good data support for developing more effective environmental and personnel fusion radiation protection.
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http://dx.doi.org/10.1088/1361-6498/abe0d1DOI Listing
January 2021

Development and Validation of an Immune-Related Gene Pair Signature in Skin Cutaneous Melanoma.

Clin Cosmet Investig Dermatol 2020 15;13:973-986. Epub 2020 Dec 15.

PET/CT Center, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Cancer Center of Yunnan Province, Kunming, Yunnan, People's Republic of China.

Introduction: Skin cutaneous melanoma (SKCM) is a common skin malignancy worldwide, and its metastasis and mortality rates are high. The molecular characteristics exhibited by tumor-immune interactions have drawn the attention from researchers. Therefore, increased knowledge and new strategies to identify effective immune-related biomarkers may improve the clinical management of SKCM by providing more accurate prognostic information.

Patients And Methods: In this study, we established a prognostic immune-related gene pair (IRGP) signature for predicting the survival of SKCM patients. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases provided gene expression profiles together with clinical information, and the samples were randomly divided into three groups including the training, testing, and validation datasets. The regression model of least absolute shrinkage and selection operator (LASSO) helped to identify a 13-IRGP signature with a significant relation to the survival of SKCM patients.

Results: The training, TCGA, and independent sets have an average value of area under the curve of 0.79, 0.76, and 0.82, respectively. In addition, this 13-IRGP signature can noticeably divide SKCM patients into high-risk group and low-risk group with significantly different prognoses. Many biological activities such as gene family were enriched among the genes in our IRGP signature. While analyzing the risk signature and clinical characteristics, there was a large difference in the risk score between T stage and tumor stage grouping. Finally, we constructed a nomogram and forest plots of the risk score and clinical features.

Conclusion: In summary, we developed a robust 13-IRGP prognostic signature in SKCM, which can identify and provide new insights into immunological biomarkers.
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http://dx.doi.org/10.2147/CCID.S281364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751297PMC
December 2020

Loss of exosomal miR-146a-5p from cancer-associated fibroblasts after androgen deprivation therapy contributes to prostate cancer metastasis.

J Exp Clin Cancer Res 2020 Dec 14;39(1):282. Epub 2020 Dec 14.

Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Wujin Road 85, Shanghai, 200080, China.

Background: Androgen deprivation therapy (ADT) is the backbone of therapy for advanced prostate cancer (PCa). Despite the good initial response, castration resistance and metastatic progression will inevitably occur. Cancer-associated fibroblasts (CAFs) may be implicated in promoting metastasis of PCa after ADT. Our aim is to investigate the role and mechanism of CAFs-derived exosomes involving in metastasis of PCa after ADT.

Methods: PCa cells were co-cultured with exosomes derived from 10 nM dihydrotestosterone (DHT)-treated (simulating the high androgen level of prostate cancer microenvironment) or ethanol (ETOH) -treated (simulating the castration level of prostate cancer microenvironment after ADT) CAFs, and their migration and invasion differences under castration condition were examined both in vitro and in vivo. The miRNA profiles of exosomes derived from DHT-treated CAFs and matched ETOH-treated CAFs were analysed via next generation sequencing. The transfer of exosomal miR-146a-5p from CAFs to PCa cells was identified by fluorescent microscopy. The function and direct target gene of exosomal miR-146a-5p in PCa cells were confirmed through Transwell assays, luciferase reporter, and western blot.

Results: Compared with DHT-treated CAFs, exosomes derived from ETOH-treated CAFs dramatically increased migration and invasion of PCa cells under castration condition. MiR-146a-5p level in exosomes from ETOH-treated CAFs was significantly reduced. The loss of miR-146a-5p may strengthen the epithelial-mesenchymal transition (EMT) to accelerate cancer cells metastasis by modulating epidermal growth factor receptor (EGFR)/ERK pathway.

Conclusions: CAFs-derived exosomal miR-146a-5p confers metastasis in PCa cells under ADT through the EGFR/ERK pathway and it may present a new treatment for PCa.
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http://dx.doi.org/10.1186/s13046-020-01761-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734763PMC
December 2020

Novel compound heterozygous variants in the STIL gene identified in a Chinese family with presentation of foetal microcephaly.

Eur J Med Genet 2020 Dec 24;63(12):104091. Epub 2020 Oct 24.

BGI-Shenzhen, Shenzhen, 518083, China. Electronic address:

Primary microcephaly 7 (MCPH7) is an autosomal recessive human neurodevelopmental disorder characterized by microcephaly, sloping forehead, and prominent midface. The STIL gene encodes a protein that regulates the mitotic spindle checkpoint. STIL is the pathogenic gene of MCPH7. Although more than 25 genes have been reported to cause MCPH, many patients lack a molecular diagnosis. The clinical manifestations and genetic factors of MCPH7 remain to be revealed. This research reported two consecutive microcephalic foetuses from unaffected parents. Prenatal ultrasound examination and pre- and postnatal MRI studies were performed. Whole-genome sequencing (WGS) was performed using blood derived from the umbilical cord, and variants were confirmed by Sanger sequencing on the parents. Ultrasound examination showed that the two foetuses suffered primary microcephaly. Using the WGS approach, novel compound heterozygous variants in STIL (c.2344_2347delTTGC, p. Leu782Thrfs*2 in exon 13; c.3838C > T, p. Arg1280Cys in exon 17) were identified in two foetuses with MCPH7. The MRI results of the two siblings were quite similar. Postnatal MRI confirmed the ultrasound and prenatal examinations. The two foetuses had typical microcephaly. Ultrasound and MRI showed that the two foetuses had a thick skull plate, significantly reduced bilateral frontal lobe, upward rotated cerebellum vermis, and dilated fourth ventricle. Our findings have important implications for prenatal diagnosis and genetic counselling for any patients with MCPH7. We extend both the mutational spectrum in the STIL gene and the clinical spectrum of MCPH7.
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http://dx.doi.org/10.1016/j.ejmg.2020.104091DOI Listing
December 2020

Characterization of Placental Microvascular Architecture by MV-Flow Imaging in Normal and Fetal Growth-Restricted Pregnancies.

J Ultrasound Med 2021 Aug 19;40(8):1533-1542. Epub 2020 Oct 19.

Fetal Heart Program, Division of Cardiology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

Objectives: To observe the microvascular architecture in the placental bed and explore the feasibility and clinical utility of MV-Flow imaging (Samsung Medison Co, Ltd, Seoul, Korea) during normal pregnancy and fetal growth restriction (FGR).

Methods: Placental microvascular structure ultrasound imaging by MV-Flow was performed on 227 unaffected and 17 FGR fetuses between 11 and 41 weeks' gestation. A placental vascular index (VI ) was acquired by application of various MV-Flow regions of interest (ellipse, rectangle, and manual trace). Unaffected control and FGR groups were assessed for umbilical artery, middle cerebral artery, and uterine artery pulsatility indices and the cerebroplacental ratio calculated by ultrasound.

Results: No significant difference in the VI by varying regions of interest or placental regions was observed in the control group. The VI in the first trimester was lower than that in the second and third trimesters, with 5th through 95th percentile normal VI reference values of 18.39 to 63.79 for 13.6 weeks and earlier, 28.53 to 66.64 for 14 weeks to 27 weeks 6 days, and 21.95 to 67.45 for 28 weeks and later. The VI values in the FGR group were lower than those in the control group in the upper, middle, and lower parts of the placenta (mean ± SD, 24.9 ± 13.9 versus 45.0 ± 13.4; P < .01; 30.5 ± 16.1 versus 44.7 ± 14.3; P < .01; and 29.9 ± 17.4 versus 47.6 ± 12.2; P < .01, respectively). Higher umbilical artery and uterine artery pulsatility indices and a lower cerebroplacental ratio were found in the FGR group compared with the control group (P < .01).

Conclusions: MV-Flow technology can display and quantify placental microvascular architecture at the level of the stem villi and villous leaves, and the VI provides for quantification of tissue vascularity. MV-Flow is a potentially powerful and promising tool to explore placental microvascular perfusion and provide new information on a host of pregnancy-related conditions.
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http://dx.doi.org/10.1002/jum.15531DOI Listing
August 2021

A new analytical platform for potential point-of-care testing of circulating tumor cells.

Biosens Bioelectron 2021 Jan 10;171:112718. Epub 2020 Oct 10.

Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, And Chemical Biology Center, College of Chemistry, Central China Normal University, Wuhan, 430079, Hubei, China. Electronic address:

It is of significance to detect circulating tumor cells (CTCs) in whole blood using transportable instruments at the point of care to assist evaluating chemotherapeutic efficacy and recurrence risk of cancer patients. However, the current widely used detection methods either require expensive and complex equipments, need complicated enrichment steps, or produce high rates of false positive and/or negative results. Aiming for solving the two critical challenges involved in instrumentation miniaturization and simplification of sample preparation for POCT of CTCs without sacrificing the detection sensitivity and accuracy, this work reports a custom-built, automatic, large field-of-view microscopic CTC cytometer and a novel enrichment strategy based on a synthesized peptide ligand discovered from One-Bead One-Compound library screening. The custom-built microscope has compact size, low weight and efficient cost while still maintaining a detection limit of as low as 5 target objects. The simplified sample preparation utilized a novel peptide LXW7 functionalized to magnetic beads and allows for rapid, highly selective and sensitive detection of CTCs. This analytical platform may fulfill the unmet need for possible point-of-care CTC counting, and provide a new option for early diagnosis of cancers and convenient evaluation of chemotherapeutic efficacy and cancer recurrence.
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http://dx.doi.org/10.1016/j.bios.2020.112718DOI Listing
January 2021

The Association Between Electronic Device Use During Family Time and Family Well-Being: Population-Based Cross-Sectional Study.

J Med Internet Res 2020 10 14;22(10):e20529. Epub 2020 Oct 14.

School of Public Health, University of Hong Kong, Hong Kong, China (Hong Kong).

Background: Electronic devices (eDevices) may have positive or negative influences on family communication and well-being depending on how they are used.

Objective: We examined eDevice use during family time and its association with the quality of family communication and well-being in Hong Kong Chinese adults.

Methods: In 2017, a probability-based 2-stage random sampling landline telephone survey collected data on eDevice use in daily life and during family time (eg, family dinner) and the presence of rules banning eDevice use during family dinner. Family communication quality was rated from 0 to 10 with higher scores being favorable. Family well-being was calculated as a composite mean score of 3 items each using the same scale from 0 to 10. The associations of family communication quality and well-being with eDevice use in daily life and during family time were estimated using beta-coefficient (β) adjusting for sociodemographics. The mediating role of family communication quality in the association between eDevice use and family well-being was analyzed.

Results: Of the 2064 respondents (mean age 56.4 [SD 19.2] years, 1269/2064 [61.48%] female), 1579/2059 (76.69%) used an eDevice daily for a mean of 3.6 hours (SD 0.1) and 257/686 (37.5%) used it for 30+ minutes before sleep. As much as 794/2046 (38.81%) often or sometimes used an eDevice during family time including dinner (311/2017, 15.42%); 713/2012 (35.44%) reported use of an eDevice by family members during dinner. Lower family communication quality was associated with hours of eDevice use before sleep (adjusted β=-.25; 95% CI -0.44 to -0.05), and often use (vs never use) of eDevice during family dinner by oneself (adjusted β=-.51; 95% CI -0.91 to -0.10) and family members (adjusted β=-.54; 95% CI -0.79 to -0.29). Similarly, lower family well-being was associated with eDevice use before sleep (adjusted β=-.26; 95% CI -0.42 to -0.09), and often use during family dinner by oneself (adjusted β=-.48; 95% CI -0.83 to -0.12) and family members (adjusted β=-.50; 95% CI -0.72 to -0.28). Total ban of eDevice use during family dinner was negatively associated with often use by oneself (adjusted odds ratio 0.49; 95% CI 0.29 to 0.85) and family members (adjusted odds ratio 0.41; 95% CI 0.28, 0.60) but not with family communication and well-being. Lower family communication quality substantially mediated the total effect of the association of eDevice use time before sleep (61.2%) and often use at family dinner by oneself (87.0%) and by family members (67.8%) with family well-being.

Conclusions: eDevice use before sleep and during family dinner was associated with lower family well-being, and the association was substantially mediated by family communication quality. Our results suggest that interventions on smart use of eDevice may improve family communication and well-being.
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http://dx.doi.org/10.2196/20529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593857PMC
October 2020
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