Publications by authors named "Bei Pan"

55 Publications

Disrupted Small-world Networks are Associated with Decreased Vigilant Attention after Total Sleep Deprivation.

Neuroscience 2021 09 19;471:51-60. Epub 2021 Jul 19.

Department of Neurology, The Second Medical Center, Sleep Medicine Research Center, National Clinical Research Centre for Geriatric Diseases, Chinese PLA General Hospital, Beijing 100853, China; School of Medicine, Nankai University, Tianjin 300071, China. Electronic address:

Sleep deprivation critically affects vigilant attention. Previous neuroimaging studies have revealed altered inter-regional functional connectivity after sleep deprivation, which may disrupt topological properties of brain functional networks. However, little is known about alterations in the topology of intrinsic connectivity and its involvement in attention performance after sleep deprivation. In the current study, we investigated the topological properties of brain networks derived from resting-state functional magnetic resonance imaging of 26 healthy men in rested wakefulness (RW) state and after 36 h of total sleep deprivation (TSD). In the predefined sparsity threshold range, both global and nodal network properties were evaluated based on graph theory analysis. Vigilant attention was assessed using the psychomotor vigilance test (PVT) before and after TSD. Furthermore, Pearson's correlation analyses were conducted to explore the association between altered network properties and changed PVT performance after TSD. At the global level, the brain functional networks in the TSD state showed a significantly lower small-world coefficient than RW, with decreased global efficiency. At the nodal level, the altered regions were selectively distributed in frontoparietal networks, sensorimotor networks, temporal regions, and salience networks. More specifically, the altered clustering coefficient in the posterior superior temporal sulcus (pSTS) and insula, and altered local efficiency in pSTS were further associated with PVT performance after TSD. Our results suggest that the topological properties of brain functional networks are disrupted, and aberrant topology of temporal networks and salience networks may act as neural signatures underlying the vigilant attention impairments after TSD.
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http://dx.doi.org/10.1016/j.neuroscience.2021.07.010DOI Listing
September 2021

Altered insula-prefrontal functional connectivity correlates to decreased vigilant attention after total sleep deprivation.

Sleep Med 2021 08 5;84:187-194. Epub 2021 Jun 5.

Department of Neurology, The Second Medical Center, Sleep Medicine Research Center, National Clinical Research Centre for Geriatric Diseases, Chinese PLA General Hospital, Beijing, 100853, China; School of Medicine, Nankai University, Tianjin, 300071, China. Electronic address:

Background: Sleep deprivation can robustly affect vigilant attention. The insula is a key hub of the salience network that mediates shifting attention between endogenous and exogenous states. However, little is known regarding the involvement of insular functional connectivity in impaired vigilant attention after total sleep deprivation (TSD). The purpose of this study is to explore the alterations in insular functional connectivity and its association with vigilant attention performance following TSD.

Methods: Twenty-six adult men were enrolled in the study. Participants underwent two counterbalanced resting-state functional magnetic resonance imaging (rs-fMRI) scans, once in rested wakefulness (RW) and once after 36 h of TSD. Seed-based functional connectivity analysis was performed using rs-fMRI data for the left and right insula. The vigilant attention was measured using a psychomotor vigilance test (PVT). Furthermore, Pearson correlation analysis was conducted to investigate the relationship between altered insular functional connectivity and PVT performance.

Results: Compared to RW, enhanced functional connectivity was observed between the insula and prefrontal cortex and anterior cingulate cortex, while reduced functional connectivity was observed between the insula and temporal, parietal, and occipital regions following TSD. Moreover, altered insular functional connectivity with the prefrontal cortex, ie superior frontal gyrus and middle frontal gyrus, and inferior temporal gyrus was correlated with PVT performance after TSD.

Conclusion: Our results suggest that insular coupling with the prefrontal cortex and inferior temporal gyrus may act as neural indicators for vigilant attention impairment, which further reveals the critical role of the salience network in cognitive decline following TSD.
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http://dx.doi.org/10.1016/j.sleep.2021.05.037DOI Listing
August 2021

Association of soft drink and 100% fruit juice consumption with all-cause mortality, cardiovascular diseases mortality, and cancer mortality: A systematic review and dose-response meta-analysis of prospective cohort studies.

Crit Rev Food Sci Nutr 2021 Jun 13:1-12. Epub 2021 Jun 13.

Gansu Provincial Hospital, Lanzhou, China.

Sugar-sweetened beverages (SSBs), artificially sweetened beverages (ASBs), and 100% fruit juices are frequently consumed and have been documented that they could lead to serious disease burden. However, inconsistent evidence on the association between SSBs, ASBs, and 100% fruit juices consumption and mortality have been presented. PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and PsycINFO were systematically searched. We conducted a random-effects meta-analysis and dose-response meta-analysis to assess the association and calculated the pooled hazard ratio with 95% confidence interval. And we evaluated the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Thirteen studies with 1,539,127 participants proved eligible. An SSB-consumption increase per 250 mL/day was associated with a 4% greater risk of all-cause mortality (5 more per 1000 persons; low certainty) and 8% greater risk of cardiovascular disease mortality (3 more per 1000 persons; low certainty). ASB-consumption increase per 250 mL/day demonstrated a 4% greater risk of all-cause mortality (5 more per 1000 persons; low certainty) and 4% greater risk of cardiovascular disease mortality (2 more per 1000 persons; low certainty). The association of SSBs and ASBs with cancer mortality was not significant, with a very low certainty of evidence. There was evidence of a linear dose-response association between SSB intake and cancer mortality, as well as between ASB intake and all-cause mortality and cancer mortality. We observed a non-linear dose-response association between ASB intake and CVD mortality and SSB intake and all-cause and CVD mortality. Low certainty of evidence demonstrated that per 250 mL/day consumption increase in SSBs and ASBs had a small impact on all-cause and cardiovascular disease mortality but not on cancer mortality. The association of 100% fruit juice consumption with all-cause and cardiovascular disease mortality was uncertain.
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http://dx.doi.org/10.1080/10408398.2021.1937040DOI Listing
June 2021

Correction for: miR-150-5p suppresses tumor progression by targeting VEGFA in colorectal cancer.

Aging (Albany NY) 2021 05 14;13(9):13372-13373. Epub 2021 May 14.

General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu, China.

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http://dx.doi.org/10.18632/aging.203069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148444PMC
May 2021

Altered functional connectivity between the nucleus basalis of Meynert and anterior cingulate cortex is associated with declined attentional performance after total sleep deprivation.

Behav Brain Res 2021 Jul 25;409:113321. Epub 2021 Apr 25.

School of Medicine, Nankai University, Tianjin, 300071, China; Department of Neurology, The Secondary Medical Center, Sleep Medicine Research Center, National Clinical Research Centre for Geriatric Diseases, Chinese PLA General Hospital, Beijing, 100853, China. Electronic address:

Background: Sleep deprivation can markedly influence vigilant attention. The nucleus basalis of Meynert (NBM), the main source of cholinergic projections to the cortex, plays an important role in wakefulness maintenance and attention control. However, the involvement of NBM in attentional impairments after total sleep deprivation (TSD) has yet to be established. The purpose of this study is to investigate the alterations in NBM functional connectivity and its association with the attentional performance following TSD.

Methods: Thirty healthy adult males were recruited in the study. Participants underwent two resting-state functional magnetic resonance imaging (rs-fMRI) scans, once in rested wakefulness (RW) and once after 36 h of TSD. Seed-based functional connectivity analysis was performed using rs-fMRI data for the left and right NBM. The vigilant attention was measured using a psychomotor vigilance test (PVT). Furthermore, Pearson correlation analysis was conducted to investigate the relationship between altered NBM functional connectivity and changed PVT performance after TSD.

Results: Compared to RW, enhanced functional connectivity was observed between right NBM and bilateral thalamus and cingulate cortex, while reduced functional connectivity was observed between left NBM and right superior parietal lobule following TSD. Moreover, altered NBM functional connectivity with the left anterior cingulate cortex was negatively correlated with PVT performance after TSD.

Conclusion: Our results suggest that the disrupted NBM-related cholinergic circuit highlights an important role in attentional performance after TSD. The enhanced NBM functional connectivity with the anterior cingulate cortex may act as neural signatures for attentional deficits induced by sleep deprivation.
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http://dx.doi.org/10.1016/j.bbr.2021.113321DOI Listing
July 2021

Successful Confinement of a Familial Cluster of COVID-19 in Qingdao, China, in the Early Phase of Pandemic.

Disaster Med Public Health Prep 2020 Dec 22:1-2. Epub 2020 Dec 22.

Municipal Centre of Disease Control and Prevention of Qingdao, Qingdao Institute of Prevention Medicine, Qingdao City, Shandong Province, People's Republic of China.

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http://dx.doi.org/10.1017/dmp.2020.489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007939PMC
December 2020

Magnetic Colloid Antibodies Accelerate Small Extracellular Vesicles Isolation for Point-of-Care Diagnostics.

Nano Lett 2021 03 16;21(5):2001-2009. Epub 2021 Feb 16.

College of Engineering and Applied Sciences, Jiangsu Key Laboratory of Artificial Functional Materials, State Key Laboratory of Analytical Chemistry for Life Science, National Laboratory of Solid State Microstructures, Nanjing University, Nanjing 210023, China.

Small extracellular vesicles (sEVs) are increasingly recognized as noninvasive diagnostic markers for many diseases. Hence, it is highly desirable to isolate sEVs rapidly for downstream molecular analyses. However, conventional methods for sEV isolation (such as ultracentrifugation and immune-based isolation) are time-consuming and expensive and require large sample volumes. Herein, we developed artificial magnetic colloid antibodies (MCAs) via surface imprinting technology for rapid isolation and analysis of sEVs. This approach enabled the rapid, purification-free, and low-cost isolation of sEVs based on size and shape recognition. The MCAs presented a higher capture yield in 20 min with more than 3-fold enrichment of sEVs compared with the ultracentrifugation method in 4 h. Moreover, the MCAs also proposed a reusability benefiting from the high stability of the organosilica recognition layer. By combining with volumetric bar-chart chip technology, this work provides a sensitive, rapid, and easy-to-use sEV detection platform for point-of-care (POC) diagnostics.
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http://dx.doi.org/10.1021/acs.nanolett.0c04476DOI Listing
March 2021

Petite miracles: insight into the nano-management of scarless wound healing.

Drug Discov Today 2021 Jan 29. Epub 2021 Jan 29.

Department of Biomedical Engineering, the Hong Kong Polytechnic University, Hung Hom, Hong Kong, China. Electronic address:

Scars affect millions of patients worldwide, yet their treatment efficacy and options clinically remain limited. In recent years, increased understanding of scar formation pathways leading to developments in nanotechnology have opened many opportunities for scar detection, prevention, and treatment due to the nanoscale features and therapeutic delivery capabilities of such technologies. Led by nanoparticles (NPs) and nanofibers, these novel strategies can aid in reducing scar contracture, improving wound-healing efficacy, and advancing progress towards scarless wound healing.
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http://dx.doi.org/10.1016/j.drudis.2021.01.025DOI Listing
January 2021

Long intergenic non-coding RNA LINC00485 exerts tumor-suppressive activity by regulating miR-581/EDEM1 axis in colorectal cancer.

Aging (Albany NY) 2021 01 10;13(3):3866-3885. Epub 2021 Jan 10.

School of Medicine, Southeast University, Nanjing 210009, Jiangsu, China.

Long non-coding RNAs (lncRNA) play a vital role in colorectal cancer (CRC) progression. To investigate the role of long intergenic non-coding RNA in CRC, we performed functional experiments. LoVo tumor-bearing and liver metastasis mice were used as models. We found that expression was significantly lower in CRC tissues and cancer cells than in paired normal samples and human normal colonic epithelial cells. Lower expression of predicted poor prognosis in CRC patients. knockdown promoted the proliferation, migration, and invasion of FHC cells, while overexpression weakened these abilities of LoVo cells. MicroRNA was the downstream target of , which was downregulated in CRC samples and cancer cells compared to normal tissues and normal colonic epithelial cells. overexpression induced proliferation, migration, and invasion of FHC cells, while antagomir treatment produced opposite results. directly targeted the 3'UTR of and inhibited its expression and induction of epithelial-mesenchymal transition of CRC. In mouse models, knockdown or down-regulation of significantly repressed CRC cell growth and prevented CRC liver metastasis. Overall, suppressed CRC tumorigenesis and progression by targeting the / axis. may be a potential therapeutic target for CRC.
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http://dx.doi.org/10.18632/aging.202354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906134PMC
January 2021

Coronavirus disease (COVID 2019): protocol for a living overview of systematic reviews.

Ann Palliat Med 2021 Feb 24;10(2):1488-1493. Epub 2020 Nov 24.

Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China; Key Laboratory of Evidence Based Medicine and Knowledge Translation of Gansu Province, Lanzhou, China; Evidence-Based Social Science Research Center, School of Public Health, Lanzhou University, Lanzhou, China.

Background: The coronavirus disease 2019 (COVID-19) pandemic continues to grow worldwide, and systematic reviews (SRs)/meta-analyses (MAs) on COVID-19 can efficiently guide evidence-based clinical practice. However, SRs/MAs with weaknesses can mislead clinical practice and pose harm to patients, and too many useless SRs/MAs could pose confusion and waste sources. A "living" overview of SRs/MAs aims to provide an open, accessible and frequently updated resource summarizing the highest-level evidence of COVID-19, that can help evidence-users to quickly identify trusted evidence to guide the practice. This study aims to systematically give an overview SRs/MAs of COVID-19, assess their quality, and identify the best synthesis of evidence.

Methods: Databases including Medline, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM) and WanFang were systematically searched on May 1, 2020 using relevant terms for identify SRs/MAs related to COVID-19. The study selection, data extraction and quality assessment will be performed by independent reviewers, and results will be crosschecked. The authoritative tools (AMSTAR-2, PRISMA and its extensions) will be used to assess the methodological quality and reporting quality of included SRs/MAs, and potential influence factors will be explored. The consistency of conclusions will be compared among reviews and the best evidence will be summarized. In addition, we will conduct exploratory meta-analyses (MAs) of individual studies when applicable. Data will be reported as number with (or) percentage, risk ratio (RR) or odds ratio (OR), mean difference (MD) or standardized mean difference (SMD) with 95% confidence interval (CI) according to the specific results. R3.6.1 and Microsoft Excel 2016 will be used to analyze and manage data.

Results: The results of this overview will be submitted to a peer-reviewed journal for publication.

Discussion: In this study, we will present for the first time, an overview of SRs/MAs, which provides a comprehensive, dynamic evidence landscape on prevalence, prevention, diagnosis, treatment, and prognosis of COVID-19.
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http://dx.doi.org/10.21037/apm-20-1130DOI Listing
February 2021

Comparison of life quality in older adults living in traditional family versus nursing home: a systematic review and meta-analysis.

Psychol Health Med 2020 Dec 14:1-12. Epub 2020 Dec 14.

Evidence-Based Social Science Center, School of Public Health, Lanzhou University, Lanzhou Gansu, China.

To assess and compare the QoL of the older people dwelling in traditional family versus nursing home/institution. A comprehensive literature search was performed on 10 January 2018 to identify studies that investigated the QoL of older adults dwelling in family versus nursing home settings. Analyses were run using random-effects meta-analyses. A total of six cross-sectional studies with 1623 people were included. The quality of included studies was moderate. Meta-analysis showed that compared with nursing home support, the family support could significantly improve the physical health (6 studies, SMD = 0.50, 95%CI: 0.32-0.68, p < 0.05), mental status (6 studies, SMD = 0.45, 95%CI: 0.26-0.65, p < 0.05), and social relationship (5 studies, SMD = 0.51, 95%CI: 0.19-0.83, p < 0.05). Traditional family support model demonstrated a significant improvement in the physical health, psychological status and social relationships among older adults. The conclusions were driven by cross-sectional studies, Larger, adequately powered RCTs are required to confirm our finding.
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http://dx.doi.org/10.1080/13548506.2020.1847303DOI Listing
December 2020

The diagnostic and prognostic values of microRNA-196a in cancer.

Biosci Rep 2021 01;41(1)

General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China.

MicroRNA-196a (miR-196a) was previously reported to be up-regulated in cancers, and it has the diagnostic and prognostic values in cancers. Whereas, the conclusion was still unclear according to the published data. To assess such roles of miR-196a in cancers, the present study was conducted based on published data and online cancer-related databases. To identify the relevant published data, we searched articles in databases and then the relevant data were extracted to evaluate the correlation between miR-196a expression and diagnosis, prognosis for cancer patients. The pooled results showed that miR-196a was a valuable diagnostic biomarker in cancer (area under curve (AUC) = 0.87, 95% CI: 0.84-0.90; sensitivity (SEN) = 0.73, 95% CI: 0.64-0.81; specificity (SPE) = 0.90, 95% CI: 0.81-0.95), which was consistent with the data from databases (breast cancer: miR-196a-3p: AUC = 0.77, 95% CI: 0.74-0.79; miR-196a-5p: AUC = 0.71, 95% CI: 0.66-0.75; pancreatic cancer: miR-196a-3p: AUC = 0.80, 95% CI: 0.73-0.87; miR-196a-5p: AUC = 0.61, 95% CI: 0.51-0.71). In addition, the pooled result revealed that elevated miR-196a expression in tumor tissues (HR = 2.54, 95% CI: 1.79-3.61, PHeterogeneity=0.000, I2 = 75.8%) or serum/plasma (HR = 4.06, 95% CI: 2.67-6.18, PHeterogeneity=0.668, I2 = 0%) of patients was an unfavorable survival biomarker, which was consistent with the data from databases (adrenocortical carcinoma: HR = 5.70; esophageal carcinoma: HR = 1.93; brain lower grade glioma: HR = 2.91; GSE40267: HR = 2.47, 95% CI: 1.2-5.07; TCGA: HR = 1.82, 95% CI: 1.21-2.74; GSE19783: HR = 4.24, 95% CI: 1-18.06). In short, our results demonstrated that miR-196a in tumor tissue or serum/plasma could be used as a prognostic and diagnostic values for cancers.
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http://dx.doi.org/10.1042/BSR20203559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791550PMC
January 2021

LncRNA SPINT1-AS1 promotes breast cancer proliferation and metastasis by sponging let-7 a/b/i-5p.

Pathol Res Pract 2021 Jan 4;217:153268. Epub 2020 Nov 4.

General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu, China. Electronic address:

Background: A growing number of studies have shown that long non-coding RNAs (lncRNAs) play an important role in the occurrence and development of tumors. In this study, we explored the function and molecular mechanism of lncRNA SPINT1-AS1 in breast cancer progression.

Methods: A total of 30 patients and 25 healthy controls were enrolled to detect the expression of SPINT1-AS1 in the serum by RT-qPCR. CCK-8 assay, clone formation assay, EdU assay, Transwell assay, Flow cytometry for apoptosis assay and wound healing assays were used to explore the effects of SPINT1-AS1 on the proliferation and migration of breast cancer cells. Bioinformatics analysis were used to enrich the downstream target genes and related pathways of miRNAs interacting with SPINT1-AS1, construct a competitive endogenous RNA (ceRNA) network diagram.

Results: SPINT1-AS1 is up-regulated in the serum of breast cancer patients and breast cancer cell lines. The proliferation and migration ability of breast cancer cells were decreased significantly after SPINT1-AS1 knockdown, and it may inhibit its expression by sponging miR-let-7a/b/i-5p, thereby promoting breast cancer progression.

Conclusions: SPINT1-AS1 can promote the proliferation and migration of breast cancer cells by regulating miR-let-7a/b/i-5p, suggesting that it may be an important regulator of breast cancer progression.
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http://dx.doi.org/10.1016/j.prp.2020.153268DOI Listing
January 2021

YTHDF1 Facilitates the Progression of Hepatocellular Carcinoma by Promoting FZD5 mRNA Translation in an m6A-Dependent Manner.

Mol Ther Nucleic Acids 2020 Dec 4;22:750-765. Epub 2020 Oct 4.

School of Medicine, Southeast University, Nanjing 210096, Jiangsu, China.

Hepatocellular carcinoma (HCC), one of the most aggressive malignancies, ranks as the fourth leading cause of cancer-related deaths worldwide. Emerging evidence indicates that RNA N6-methyladenosine (m6A) plays a critical role in tumor progression. However, the biological function of YTHDF1 in HCC remains unclear. Here, we found that YTHDF1 expression was strikingly elevated in HCC tissues and cell lines and significantly associated with prognosis of HCC patients. Moreover, YTHDF1 expression was transcriptionally regulated by USF1 and c-MYC in HCC. Functional studies showed that YTHDF1 can promote HCC cell proliferation and metastasis both and . Multi-omics analysis revealed that YTHDF1 can accelerate the translational output of FZD5 mRNA in an m6A-dependent manner and function as an oncogene through the WNT/β-catenin pathway. Taken together, our study revealed an essential role of YTHDF1 in the progression of HCC cells, which indicated that targeting YTHDF1 may be a potential therapeutic strategy in HCC.
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http://dx.doi.org/10.1016/j.omtn.2020.09.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595883PMC
December 2020

Analysis of METTL3 and METTL14 in hepatocellular carcinoma.

Aging (Albany NY) 2020 11 6;12(21):21638-21659. Epub 2020 Nov 6.

School of Medicine, Southeast University, Nanjing 210096, Jiangsu, China.

N6-methyladenosine (m6A) RNA methylation is the most prevalent modification of messenger RNAs (mRNAs) and catalyzed by a multicomponent methyltransferase complex (MTC), among which methyltransferase-like 3 (METTL3) and METTL14 are two core molecules. However, METTL3 and METTL14 play opposite regulatory roles in hepatocellular carcinoma (HCC). Based on The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database, we conducted a multi-omics analysis of METTL3 and METTL14 in HCC, including RNA-sequencing, m6ARIP-sequencing, and ribosome-sequencing profiles. We found that the expression and prognostic value of METTL3 and METTL14 are opposite in HCC. Besides, after METTL3 and METTL14 knockdown, most of the dysregulated mRNAs, signaling pathways and biological processes are distinct in HCC, which partly explains the contrary regulatory role of METTL3 and METTL14. Intriguingly, these mRNAs whose stability or translation efficiency are influenced by METTL3 or METTL14 in an m6A dependent manner, jointly regulate multiple signaling pathways and biological processes, which supports the cooperative role of METTL3 and METTL14 in catalyzing m6A modification. In conclusion, our study further clarified the contradictory role of METTL3 and METTL14 in HCC.
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http://dx.doi.org/10.18632/aging.103959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695415PMC
November 2020

Susceptibility of / Genetic Variations to Ischemic Stroke Risk in a Chinese Han Population.

Pharmgenomics Pers Med 2020 29;13:563-570. Epub 2020 Oct 29.

Department of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, People's Republic of China.

Background: Paraoxonases (PONs) are a family of orphan enzymes with multiple functions, including anti-inflammatory, antioxidative, antiatherogenic activities. Studies have suggested that genetic variations in and are associated with ischemic stroke (IS) risk; however, the conclusion remains unclear in the Chinese population.

Methods: To investigate the susceptibility of genetic variations in and to risk of IS and its subtypes, this case-control study was carried out on a Chinese population comprising 300 IS patients and 300 healthy controls. Genotypes of six genetic variations in and were identified with an improved multiplex ligase detection-reaction technique.

Results: rs662 was associated with increased risk of IS (CT vs. TT - OR 1.79, 95% CI 1.08-2.97; =0.025). Stratified analysis for patients by sex revealed that the significant association of rs662 with IS risk was maintained in the male cohort (CT vs. TT - OR 2.59, 95% CI 1.29-5.21 [=0.009]; CT/CC vs. TT - OR 2.03, 95% CI 1.05-3.93 [=0.036]), but not in the female cohort. Analysis according to IS subtype revealed that rs662 genetic variation was an increased risk in the subcohort of patients with large-artery atherosclerosis (CT/CC vs. TT - OR 2.31, 95% CI 1.09-4.91; =0.029), but not in patients with other types of IS.

Conclusion: This study suggested that rs662 presented a potential risk of IS, especially for males, and this association was more obvious for large-artery atherosclerosis.
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http://dx.doi.org/10.2147/PGPM.S275341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605958PMC
October 2020

The distribution of SARS-CoV-2 contamination on the environmental surfaces during incubation period of COVID-19 patients.

Ecotoxicol Environ Saf 2021 Jan 30;208:111438. Epub 2020 Sep 30.

Municipal Centre of Disease Control and Prevention of Qingdao, Qingdao Institute of Prevention Medicine, Qingdao, Shandong Province, China. Electronic address:

Roles of environmental factors in transmission of COVID-19 have been highlighted. In this study, we sampled the high-touch environmental surfaces in the quarantine room, aiming to detect the distribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the environmental surfaces during the incubation period of coronavirus disease 2019 (COVID-19) patients. Fifteen sites were sampled from the quarantine room, distributing in the functional areas such as bedroom, bathroom and living room. All environmental surface samples were collected with sterile polyester-tipped applicator pre-moistened in viral transport medium and tested for SARS-CoV-2. Overall, 34.1% of samples were detected positively for SARS-CoV-2. The positive rates of Patient A, B and C, were 46.2%, 0% and 61.5%, respectively. SARS-CoV-2 was detected positively in bedroom and bathroom, with the positive rate of 50.0% and 46.7%, respectively. In contrast, living room had no positive sample detected. Environmental contamination of SARS-CoV-2 distributes widely during the incubation period of COVID-19, and the positive rates of SARS-CoV-2 on environmental surfaces are relatively high in bathroom and bedroom.
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http://dx.doi.org/10.1016/j.ecoenv.2020.111438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526608PMC
January 2021

Analysis of the status quo of the Elderly's demands of medical and elderly care combination in the underdeveloped regions of Western China and its influencing factors: a case study of Lanzhou.

BMC Geriatr 2020 09 9;20(1):338. Epub 2020 Sep 9.

Gansu Provincial Hospital, Lanzhou, 730050, People's Republic of China.

Background: This study aims to analyse the current demand by senior citizens in Lanzhou, China for a combination of medical and elderly care services and to identify the factors influencing their needs.

Methods: 7500 participants aged 60 or above living in Lanzhou, China, were recruited, a unified questionnaire concerning elderly people's demand for a service combining medical and elderly care has been adopted to survey these subjects. The status quo of the demand of the service combining medical and elderly care and its influencing factors were analysed with the single-factor Chi-square test and multi-factor binomial logistic regression method.

Results: 3772 of 7320 older people have the demand for the service combining medical and elderly care, accounting for 53.15% of survey respondents. Many factors are in play, including gender, marital status, degree of education, occupation before retirement, number of children, monthly income, health self-assessment status, endowment insurance type, medical insurance type, current nursing arrangements, old-age demands, self-care ability and the knowledge of combining medical and elderly care and the willingness to pay for the combination of medical and elderly care have statistical significance (P < 0.05) with the elderly's needs, different ages, living styles and the prevalence of chronic diseases, have no statistical significance (P > 0.05) with the elderly's care needs in Lanzhou. The number of children, type of medical insurance and willingness to pay for the combination of medical treatment and nursing care are major influencing factors among the complex factors influencing the elderly's demand for the proposed service.

Conclusions: The low knowledge rate and demand rate, the number of children, the type of medical insurance, and the willingness to pay for the medical-nursing combination service for the elderly in Lanzhou have a great impact on the elderly's demand rate for combining medical and elderly care. Meanwhile, relevant government departments should focus more on the promotion of the endowment model of combining medical and elderly care and provide integrated medical care services by integrating multiple resources, and improving social security.
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http://dx.doi.org/10.1186/s12877-020-01616-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488146PMC
September 2020

Enteral Lactoferrin Supplementation for Preventing Sepsis and Necrotizing Enterocolitis in Preterm Infants: A Meta‑Analysis With Trial Sequential Analysis of Randomized Controlled Trials.

Front Pharmacol 2020 7;11:1186. Epub 2020 Aug 7.

Evidence-Based Social Science Research Center, School of Public Health, Lanzhou University, Lanzhou, China.

Background: Several clinical trials investigated the effects of enteral lactoferrin supplementation on the prevention of sepsis and necrotizing enterocolitis (NEC) in preterm infants, but the efficacy and safety remain disputed. Therefore, we systematically evaluated the effect of enteral lactoferrin supplementation in preterm infants through a meta‑analysis with trial sequential analysis (TSA).

Methods: We searched six databases to identify randomized controlled trials (RCTs) that evaluated the effects of lactoferrin supplementation compared with placebo or no intervention in preterm infants. RevMan version 5.3 software was used to estimate pooled relative risks (RRs) with the random-effects model. TSA, subgroup analyses, and meta-regression analyses were also performed.

Results: Nine RCTs with 3515 samples were included. With low to moderate quality of evidence, compared with placebo, enteral lactoferrin supplementation did not significantly decrease the incidences of late-onset sepsis (RR = 0.63, 95% CI: 0.38 to 1.02, = 0.06), NEC stage II or III (RR = 0.68, 95% CI: 0.30 to 1.52, = 0.35), all-cause mortality (RR = 0.89, 95% CI: 0.51 to 1.57, = 0.69), bronchopulmonary dysplasia (RR = 1.01, 95% CI: 0.90 to 1.13, = 0.92), retinopathy of prematurity (RR = 0.80, 95% CI: 0.49 to 1.32, = 0.38), invasive fungal infection (RR = 0.27, 95% CI: 0.02 to 3.94, = 0.34), intraventricular hemorrhage (RR = 1.40, 95% CI: 0.39 to 5.08, = 0.61), and urinary tract infection (RR = 0.35, 95% CI: 0.11 to 1.06, = 0.06). Subgroup analysis revealed that lactoferrin significantly reduced the incidence of sepsis in infants with a birth weight below 1500 g (RR = 0.43, 95% CI: 0.22 to 0.84, = 0.01). TSAs of the primary outcomes showed that the evidence is insufficient and further data is required.

Conclusions: Limited evidence suggested that enteral lactoferrin supplementation was associated with a reduction of late-onset sepsis in infants with a birth weight below 1500g, however, did not decrease the incidence of NEC stage II or III, all-cause mortality, and other adverse events in preterm infants. The present evidence was insufficient to inform clinical practice.
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http://dx.doi.org/10.3389/fphar.2020.01186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426497PMC
August 2020

METTL14-mediated N6-methyladenosine modification of SOX4 mRNA inhibits tumor metastasis in colorectal cancer.

Mol Cancer 2020 06 17;19(1):106. Epub 2020 Jun 17.

General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, No. 68, Changle Road, Nanjing, 210006, China.

Background: Colorectal cancer (CRC) is one of the leading causes of tumor-related death worldwide, and its main cause of death is distant metastasis. Methyltransferase-like 14(METTL14), a major RNA N6-adenosine methyltransferase, is involved in tumor progression via regulating RNA function. The goal of the study is to uncover the biological function and molecular mechanism of METTL14 in CRC.

Methods: Quantitative real-time PCR (qRT-PCR), western blot and immunohistochemical (IHC) assays were employed to detect METTL14 and SOX4 in CRC cell lines and tissues. The biological functions of METTL14 were demonstrated using in vitro and in vivo experiments. Chromatin immunoprecipitation (ChIP), Transcrptomic RNA sequencing (RNA-Seq), m6A-RNA immunoprecipitation sequencing (MeRIP-Seq), RNA immunoprecipitation and luciferase reporter assays were used to explore the mechanism of METTL14 action.

Results: METTL14 expression was significantly downregulated in CRC and decreased METTL14 was associated with poor overall survival (OS). Both the univariate and multivariate Cox regression analysis indicated that METTL14 was an independent prognostic factor in CRC. Moreover, lysine-specific histone demethylase 5C(KDM5C)-mediated demethylation of histone H3 lysine 4 tri-methylation(H3K4me3) in the promoter of METTL14 inhibited METTL14 transcription. Functionally, we verified that METTL14 inhibited CRC cells migration, invasion and metastasis through in vitro and in vivo assays, respectively. Furthermore, we identified SRY-related high-mobility-group box 4(SOX4) as a target of METTL14-mediated m6A modification. Knockdown of METTL14 markedly abolished SOX4 mRNA m6A modification and elevated SOX4 mRNA expression. We also revealed that METTL14-mediated SOX4 mRNA degradation relied on the YTHDF2-dependent pathway. Lastly, we demonstrated that METTL14 might inhibit CRC malignant process partly through SOX4-mediated EMT process and PI3K/Akt signals.

Conclusions: Decreased METTL14 facilitates tumor metastasis in CRC, suggesting that METTL14 might be a potential prognostic biomarker and effective therapeutic target for CRC.
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http://dx.doi.org/10.1186/s12943-020-01220-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298962PMC
June 2020

Prevalence of frailty in China: Protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2020 May;99(20):e20079

Gansu Provincial Hospital, Lanzhou, China.

Introduction: China is facing more and more enormous challenges including aging, the increase of social security costs and health care cost, decrease of labors, and how to keep elders' capacity to function well and live independently. Healthy aging has become an extremely challenging issue. Frailty, a geriatric syndrome resulted from the declines of multiple physiological systems, characterized by malnutrition, exercise intolerance, dependence, longer bed rest, lower gaits peed, weakness, weight loss, anorexia, hip fracture, risk of falling, delirium, dementia, and keep indoors, has become one of the biggest challenges in facilitating healthy aging. Because the research of frailty just had started in recent years in China, the evidence regarding the prevalence of frailty among the Chinese population is scarce and just limited in certain area.

Method: We will systematically search 7 electronic database including PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Web of science, MEDLINE, CNKI (Chinese National Knowledge Infrastructure), and CBM (Chinese Biological Medical Database) to identify studies that provide or potential available of data regarding to prevalence of frailty. Risk of bias of individual study will be assessed using 8-iterm critical appraisal criteria for prevalence or incidence studies. Data will be analyzed using STATA V.12.0 software.

Conclusions: Our systematic review and meta-analysis will firstly pool the results from available studies to provide a comprehensive evidence for the prevalence of frailty. The results of this study will be submitted to a peer-reviewed journal for publication.
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http://dx.doi.org/10.1097/MD.0000000000020079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7254570PMC
May 2020

WITHDRAWN: Petite miracles: insight into the nano-management of scarless wound healing.

Drug Discov Today 2020 09 6;25(9):1772. Epub 2020 Apr 6.

Department of Biomedical Engineering, the Hong Kong Polytechnic University, Hung Hom, Hong Kong, China. Electronic address:

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.
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http://dx.doi.org/10.1016/j.drudis.2020.03.013DOI Listing
September 2020

LRIG3 represses cell motility by inhibiting slug via inactivating ERK signaling in human colorectal cancer.

IUBMB Life 2020 07 27;72(7):1393-1403. Epub 2020 Feb 27.

School of Medicine, Southeast University, Nanjing, China.

Metastasis is responsible for 90% of colorectal cancer (CRC)-related deaths. In the present study, we identified a novel key regulator of CRC metastasis, leucine-rich repeats and immunoglobulin-like domains protein 3 (LRIG3), which was significantly decreased in CRC tissues and cell lines. Downregulation of LRIG3 was attributed to copy number loss and promoter hypermethylation. Low LRIG3 expression was positively correlated with metastatic clinical features and shorter survival time. Functional experiments showed that knockout of LRIG3 markedly enhanced CRC cell migration and invasion ability, whereas reintroduction of LRIG3 exerted the opposite effects. Regarding the mechanism, LRIG3 could facilitate the binding of DUSP6 to ERK1/2, resulting in the dephosphorylation of ERK1/2 and subsequently downregulation of slug, an epithelial-to-mesenchymal transition trigger, thereby constraining CRC cell motility. Importantly, LRIG3 expression was strongly negatively correlated with slug or p-ERK1/2 expression in CRC tissues. Collectively, our data suggest that LRIG3 is a novel suppressor of CRC metastasis, reactivation of LRIG3 may be a promising therapeutic approach for metastatic CRC patients.
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http://dx.doi.org/10.1002/iub.2262DOI Listing
July 2020

Health education interventions for older adults with hypertension: A systematic review and meta-analysis.

Public Health Nurs 2020 05 13;37(3):461-469. Epub 2020 Jan 13.

Department of Social Medicine and Health Management, School of Public Health, Lanzhou University, Lanzhou, China.

Objective: The study aimed to evaluate the effectiveness of health education intervention for the control of blood pressure (BP) in older adults with hypertension.

Methods: Five databases were searched in March 2018 for randomized controlled trials to manage hypertension in older adults by health education. The primary outcomes were changes in systolic and diastolic BP. RevMan5 was used for meta-analysis.

Results: Seven articles with 1,105 participants were included. In them, 393 (35.56%) older adults participated in health education interventions in the form of courses, and 226 (20.45%), in health education sessions. The meta-analysis suggested an overall reduction in systolic BP after health education courses (SMD, standardized mean difference = 4.80, 95% CI: 7.01-2.59, p < .05). Similar results were observed after health education sessions (SMD = 11.73, 95% CI: 17.63-5.82, p < .05). The diastolic BP reduction showed no difference after the health education course (p = .09). The random effects meta-analysis suggested an overall reduction in diastolic BP after health education sessions (SMD = 5.39, 95% CI: 7.98-2.79, p < .05).

Conclusion: Although different health education methods had different effects on hypertension control, overall, educational interventions can potentially lead to improved BP control.
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http://dx.doi.org/10.1111/phn.12698DOI Listing
May 2020

Serum exosomal miR-122 as a potential diagnostic and prognostic biomarker of colorectal cancer with liver metastasis.

J Cancer 2020 1;11(3):630-637. Epub 2020 Jan 1.

Department of General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

: Liver is the most common site for metastatic spread of CRC at the time of diagnosis which leads to high mortality. This study aimed to identify novel circulating exosomal miRNAs as biomarkers of colorectal cancer (CRC) with liver metastasis (LM). : Candidate miRNAs were selected through integrated analysis of Gene Expression Omnibus (GEO) database as well as clinical samples. Exosomes isolated from serum and cultured media were identified by using transmission electron microscopy (TEM) and western blot. The expression levels and diagnostic value of candidate miRNAs were further tested and validated through qRT-PCR and receiver operating characteristic curve (ROC) analysis. The association of candidate miRNA expressions with patients' prognosis was analyzed with logistic regression and Cox proportional hazards regression models. : After integrated analysis of three GEO datasets and clinical samples, miR-122 was discovered to be remarkably overexpressed in tissues of CRC patients. Then we revealed that elevated serum miR-122 was tumor-derived by being packaged into exosomes. The expressions of serum exosomal miR-122 were significantly upregulated in CRC patients, especially in those with LM. Serum exosomal miR-122 expressions could differentiate CRC patients with LM from healthy controls and patients without LM with area under the ROC curve (AUC) of 0.89 and 0.81. Uni- and multivariate logistic regression showed that serum exosomal miR-122 was an independent prognostic indicator of CRC patients. Serum exosomal miR-122 was a novel potential diagnostic and prognostic biomarker in CRC patients with LM.
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http://dx.doi.org/10.7150/jca.33022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6959047PMC
January 2020

Reply to Wu et al.: Commentary on insomnia and risk of mortality.

Sleep Med Rev 2020 04 27;50:101256. Epub 2019 Dec 27.

Department of Social Medicine and Health Management, School of Public Health, Lanzhou University, Lanzhou, 730000, China. Electronic address:

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http://dx.doi.org/10.1016/j.smrv.2019.101256DOI Listing
April 2020

Non-pharmacological interventions for older adults with depressive symptoms: a network meta-analysis of 35 randomized controlled trials.

Aging Ment Health 2021 05 27;25(5):773-786. Epub 2019 Dec 27.

Department of Social Medicine and Health Management, School of Public Health, Lanzhou University, Lanzhou, China.

To assess the effectiveness of non-pharmacological interventions for seniors with depressive symptoms. A comprehensive literature search was performed. We conducted network meta-analysis in two ways, intervention classes (psychosocial, psychotherapy, physical activity, combined, treatment as usual) and individual intervention (11 categories). Whenever included studies used different scales, the different instruments were converted to the units of the scale most frequently used (the Geriatric Depression Scale), such that the effect size was reported as a mean difference (MD) with 95% confidence interval (CI). The risk of bias of RCTs included in this review was assessed according to the Cochrane Handbook. Bayesian NMA was conducted using R-3.4.0 software. A total of 35 RCTs with 3,797 enrolled patients were included. Compared to conventional treatment, physical activity and psychotherapy resulted in significant improvements in depressive symptoms (MD: 2.25, 95%CrI: 0.99-3.56; SUCRA = 86.07%; MD: 1.75, 95% CrI: 0.90-2.64; SUCRA = 66.44%, respectively). Similar results were obtained for music (MD: 2.6; 95% CrI: 0.84-4.35;SUCRA = 80.53%), life review (MD:1.92; 95% CrI:0.71-3.14; SUCRA = 65.62%), cognitive behavioral therapy (MD: 1.27; 95% CrI: 0.23-2.38; SUCRA = 45.4%), aerobic (MD: 1.84; 95% CrI: 0.39-3.36; SUCRA = 63%) and resistance training (MD: 1.72; 95% CrI: 0.06-3.42; SUCRA = 59.24%). Network meta-regression showed that there were no statistically significant subgroup effects. Physical activity and psychotherapy demonstrated statistically significant superiority over conventional treatment. Music and life review therapy proved the most promising individual interventions. However, conclusions are limited by the lack of sufficient sample size and consensus regarding intervention categories and so an adequately powered study is necessary to consolidate these findings.
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http://dx.doi.org/10.1080/13607863.2019.1704219DOI Listing
May 2021

METTL14 Suppresses CRC Progression via Regulating N6-Methyladenosine-Dependent Primary miR-375 Processing.

Mol Ther 2020 02 20;28(2):599-612. Epub 2019 Nov 20.

General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu, China. Electronic address:

Epigenetic alterations contributed to human carcinogenesis immensely. N6-methyladenosine (m6A) is one of the most preventive and abundant modifications on RNA molecules present in eukaryotes. However, the biological function of m6A methylation in colorectal cancer (CRC) remains largely unclear. Here, we found that METTL14 was downregulated in CRC tissues and cell lines, and closely correlated with overall survival (OS). METTL14 knockdown significantly reduced m6A levels in total RNAs and promoted CRC cell growth and metastasis, whereas METTL14 overexpression markedly increased m6A levels in total RNA and inhibited CRC cell growth and metastasis. Furthermore, we demonstrated that miR-375 was a downstream target of METTL14. We also verified that METTL14 suppressed CRC cell growth via the miR-375/Yes-associated protein 1 (YAP1) pathway, as well as inhibited CRC cell migration and invasion through the miR-375/SP1 pathway. Taken together, our studies showed an important role for METTL14 in CRC progression and provided novel insight into m6A modification in CRC progression.
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http://dx.doi.org/10.1016/j.ymthe.2019.11.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001002PMC
February 2020

Identification of Serum Exosomal hsa-circ-0004771 as a Novel Diagnostic Biomarker of Colorectal Cancer.

Front Genet 2019 1;10:1096. Epub 2019 Nov 1.

General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.

Exosomal circular RNAs (circRNAs) in peripheral blood are considered as emerging diagnostic biomarkers of cancers. Owing to the lack of sensitive and specific biomarkers, a large number of colorectal cancer (CRC) patients were diagnosed in advanced stages leading to high mortality. This study aimed to identify circulating exosomal circRNAs as novel diagnostic biomarkers of CRC. Candidate circRNA was selected by integrating analysis of Gene Expression Omnibus (GEO) database with online program GEO2R. A total of 170 patients and 45 healthy controls were enrolled to assess the diagnostic value of circRNAs for CRC. Exosomes isolated from the serum of participants and cell cultured media were confirmed by transmission electron microscope (TEM), Nanoparticle Tracking Analysis and western blot. The expression and the diagnostic utility of circRNA were tested by qRT-PCR and receiver operating characteristic (ROC) analysis, respectively. The circulating exosomal hsa-circ-0004771 with most abundant among the top ten differentially expressed circRNAs (fold change ≥1.5) was selected for further study based on the results of GEO dataset analysis. The up-regulated exosomal hsa-circ-0004771 was verified in serum of CRC patients compared to healthy controls (HCs) and patients with benign intestinal diseases (BIDs) by qRT-PCR. The area under the ROC curves (AUCs) of circulating exosomal hsa-circ-0004771 were 0.59 (95%CI, 0.457-0.725), 0.86 (95%CI, 0.785-0.933) and 0.88 (95%CI, 0.815-0.940) to differentiate BIDs, stage I/II CRC patients and CRC patients from HCs, respectively. The AUC was 0.816 (95%CI, 0.728-0.9) to differentiate stage I/II CRC patients from patients with BIDs. In addition, the elevated expression of exosomal hsa-circ-0004771 in the serum of CRC patients was tumor-derived. It was found that the expression of exosomal hsa-circ-0004771 was down-regulated expression of in the serum of postoperative CRC patients as well as cultured media of CRC cells treated with GW4869. Circulating exosomal hsa-circ-0004771 was significantly up-regulated in CRC patients and served as a novel potential diagnostic biomarker of CRC.
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http://dx.doi.org/10.3389/fgene.2019.01096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6838203PMC
November 2019

MiR-142-3p functions as a tumor suppressor by targeting RAC1/PAK1 pathway in breast cancer.

J Cell Physiol 2020 05 31;235(5):4928-4940. Epub 2019 Oct 31.

General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.

MicroRNA-142-3p (miR-142-3p) was previously investigated in various cancers, whereas, it's role in breast cancer (BC) remains far from understood. In this study, we found that miR-142-3p was markedly decreased both in cell lines and BC tumor tissues. Elevated miR-142-3p expression suppressed growth and metastasis of BC cell lines via gain-of-function assay in vitro and in vivo. Mechanistically, miR-142-3p could regulate the ras-related C3 botulinum toxin substrate 1 (RAC1) expression in protein level, which simultaneously suppressed the epithelial-to-mesenchymal transition related protein levels and the activity of PAK1 phosphorylation, respectively. In addition, rescue experiments revealed RAC1 overexpression could reverse tumor-suppressive role of miR-142-3p. Our results showed miR-142-3p could function as a tumor suppressor via targeting RAC1/PAK1 pathway in BC, suggesting a potent therapeutic target for BC treatment.
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http://dx.doi.org/10.1002/jcp.29372DOI Listing
May 2020
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