Publications by authors named "Xiaoyan Lu"

241 Publications

Identify differential genes and cell subclusters from time-series scRNA-seq data using scTITANS.

Comput Struct Biotechnol J 2021 26;19:4132-4141. Epub 2021 Jul 26.

Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.

Time-series single-cell RNA sequencing (scRNA-seq) provides a breakthrough in modern biology by enabling researchers to profile and study the dynamics of genes and cells based on samples obtained from multiple time points at an individual cell resolution. However, cell asynchrony and an additional dimension of multiple time points raises challenges in the effective use of time-series scRNA-seq data for identifying genes and cell subclusters that vary over time. However, no effective tools are available. Here, we propose scTITANS (https://github.com/ZJUFanLab/scTITANS), a method that takes full advantage of individual cells from all time points at the same time by correcting cell asynchrony using pseudotime from trajectory inference analysis. By introducing a time-dependent covariate based on time-series analysis method, scTITANS performed well in identifying differentially expressed genes and cell subclusters from time-series scRNA-seq data based on several example datasets. Compared to current attempts, scTITANS is more accurate, quantitative, and capable of dealing with heterogeneity among cells and making full use of the timing information hidden in biological processes. When extended to broader research areas, scTITANS will bring new breakthroughs in studies with time-series single cell RNA sequencing data.
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http://dx.doi.org/10.1016/j.csbj.2021.07.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8342909PMC
July 2021

scDeepSort: a pre-trained cell-type annotation method for single-cell transcriptomics using deep learning with a weighted graph neural network.

Nucleic Acids Res 2021 Sep 9. Epub 2021 Sep 9.

Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.

Advances in single-cell RNA sequencing (scRNA-seq) have furthered the simultaneous classification of thousands of cells in a single assay based on transcriptome profiling. In most analysis protocols, single-cell type annotation relies on marker genes or RNA-seq profiles, resulting in poor extrapolation. Still, the accurate cell-type annotation for single-cell transcriptomic data remains a great challenge. Here, we introduce scDeepSort (https://github.com/ZJUFanLab/scDeepSort), a pre-trained cell-type annotation tool for single-cell transcriptomics that uses a deep learning model with a weighted graph neural network (GNN). Using human and mouse scRNA-seq data resources, we demonstrate the high performance and robustness of scDeepSort in labeling 764 741 cells involving 56 human and 32 mouse tissues. Significantly, scDeepSort outperformed other known methods in annotating 76 external test datasets, reaching an 83.79% accuracy across 265 489 cells in humans and mice. Moreover, we demonstrate the universality of scDeepSort using more challenging datasets and using references from different scRNA-seq technology. Above all, scDeepSort is the first attempt to annotate cell types of scRNA-seq data with a pre-trained GNN model, which can realize the accurate cell-type annotation without additional references, i.e. markers or RNA-seq profiles.
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http://dx.doi.org/10.1093/nar/gkab775DOI Listing
September 2021

A Study Protocol for a Randomized, Double-Blind, Placebo-Controlled Clinical Study on the Effect of Qishen Yiqi Dripping Pills on Exercise Endurance and Quality of Life in Patients with Coronary Heart Disease after Percutaneous Coronary Intervention.

Evid Based Complement Alternat Med 2021 24;2021:7439852. Epub 2021 Aug 24.

China-Japan Friendship Hospital, Beijing, China.

Background: Percutaneous coronary intervention (PCI) is widely used in China, but it does not fundamentally improve exercise endurance or reduce mortality associated with cardiovascular disease. Standardized cardiac rehabilitation (CR) can reduce the mortality associated with coronary heart disease and reduce the need for repeated PCI procedures. Currently, research on CR after PCI is mainly based on traditional exercise prescription, while research on TCM is limited. Often, the combination of traditional Chinese medicine (TCM) and exercise rehabilitation is adopted, from which it is difficult to determine the unique advantages of TCM. Qishen Yiqi dripping pills (QSYQ) can improve myocardial energy metabolism and alleviate myocardial reperfusion injury after PCI. This paper describes the protocol for the clinical assessment of QSYQ on CR.

Methods: A randomized, double-blind, placebo-controlled trial will be used to evaluate the efficacy and safety of QSYQ on improving exercise endurance and quality of life. We plan to recruit 66 patients with stable angina pectoris with Qi deficiency and blood stasis syndrome differentiation after PCI from the China-Japan Friendship Hospital. On the basis of conventional drug treatment, QSYQ or placebo will be used for 12 weeks. PeakVO will be the main efficacy evaluation index, while Seattle scale and quality of life scale will be the secondary efficacy evaluation indexes. . CR therapy with integrated traditional Chinese and Western medicine has been developed as a treatment modality in China and has been included in the expert consensus of TCM diagnosis and treatment. A rigorous trial design will ensure objective and scientific evaluation of the efficacy and safety of QSYQ in improving exercise endurance and quality of life in patients with PCI. . This trial is registered with Clinical trial registration in China: ChiCTR2000040838 (registration date: December 11, 2020).
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http://dx.doi.org/10.1155/2021/7439852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8407996PMC
August 2021

Design, methodology, and baseline of whole city-million scale children and adolescents myopia survey (CAMS) in Wenzhou, China.

Eye Vis (Lond) 2021 Aug 19;8(1):31. Epub 2021 Aug 19.

School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China.

Background: Myopia is the most common visual impairment in children and adolescents worldwide. This study described an economical and effective population-based screening pipeline and performed the project of a million scale children and adolescents myopia survey (CAMS), which will shed light on the further study of myopia from the level of epidemiology and precision medicine.

Methods: We developed a novel population-based screening pattern, an intelligent screening process and internet-based information transmission and analysis system to carry out the survey consisting of school children in Wenzhou, China. The examination items include unaided distance visual acuity, presenting distance visual acuity, and non-cycloplegic autorefraction. Myopia and high myopia were defined as spherical equivalent (SE) ≤ - 1.00 diopters (D) and SE ≤ - 6.00 D, respectively. Next, the reports of the vision checking were automatically sent to parents and the related departments. The CAMS project will be done two to four times annually with the support of the government. An online eyesight status information management system (OESIMS) was developed to construct comprehensive and efficient electronic vision health records (EVHRs) for myopia information inquiry, risk pre-warning, and further study.

Results: The CAMS completed the first-round of screening within 30 days for 99.41% of Wenzhou students from districts and counties, in June 2019. A total of 1,060,925 participants were eligible for CAMS and 1,054,251 (99.37% participation rate) were selected through data quality control, which comprised 1305 schools, and 580,609, 251,050 and 170,967 elementary, middle, and high school students. The mean age of participants was 12.21 ± 3.32 years (6-20 years), the female-to-male ratio was 0.82. The prevalence of myopia in elementary, middle, and high school students was 38.16%, 77.52%, and 84.00%, respectively, and the high myopia incidence was 0.95%, 6.90%, and 12.98%.

Conclusions: The CAMS standardized myopia screening model involves automating large-scale information collection, data transmission, data analysis and early warning, thereby supporting myopia prevention and control. The entire survey reduced 90% of staff, cost, and time consumption compared with previous surveys. This will provide new insights for decision support for public health intervention.
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http://dx.doi.org/10.1186/s40662-021-00255-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373605PMC
August 2021

Human Adenovirus 11 in 2 Renal Transplant Recipients: Suspected Donor-Derived Infection.

Open Forum Infect Dis 2021 Mar 25;8(3):ofab092. Epub 2021 Feb 25.

Division of Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia, USA.

Background: Human adenovirus (HAdV) infections can lead to high mortality in solid organ transplant (SOT) recipients, with rare reports of donor-derived infection.

Methods: Two renal transplant recipients with HAdV-11 infection who received kidneys from the same donor are described. Whole-genome sequencing (WGS) was performed.

Results: WGS showed 100% nucleotide sequence identity for the 2 HAdV-11 isolates. The patients presented with distinct clinical syndromes, and both were treated with brincidofovir.

Conclusions: Donor-derived HAdV infection is presumed to be low; however, disseminated HAdV in SOT recipients can be severe, and clinicians should be aware of the clinical course and treatment options.
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http://dx.doi.org/10.1093/ofid/ofab092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355461PMC
March 2021

Risk factors for oral mucositis in patients with malignant tumors: a prospective cohort study.

Ann Palliat Med 2021 Jul;10(7):8180-8189

Department of Oncology Radiotherapy, Affiliated Hospital of Nantong University, Nantong, China.

Background: To investigate the incidence and risk factors of oral mucositis in patients with malignant tumors.

Methods: A total of 74 patients with malignant tumors who were hospitalized in the Affiliated Hospital of Nantong University from January 2020 to December 2020 were selected and divided into two groups according to whether oral mucositis occurred (n=45) or not (n=29). Chi-square test was used to compare the general data between the two groups, and multivariate logistic regression analysis was used to investigate the risk factors of oral mucositis in patients with malignant tumors.

Results: Oral mucositis occurred in 45 of 74 malignant tumor patients (60.8%), and the incidence in patients with head and neck tumors was significantly higher than in those with chest and abdomen tumors (P<0.05). A significantly higher incidence was also seen in patients with poor oral cleanliness in comparison to those with high oral cleanliness; in radiotherapy patients in comparison to non-radiotherapy patients; in patients who received Nituzumab during radiotherapy in comparison to those who did not, and in patients receiving eight cycles of chemotherapy in comparison to those not receiving chemotherapy. Multivariate logistic regression analysis showed that oral cleanliness, radiotherapy, and duration of radiotherapy were independent risk factors for oral mucositis in patients with malignant tumors (P<0.05).

Conclusions: Poor oral cleanliness, radiotherapy, and longer duration of radiotherapy lead to the occurrence of oral mucositis in patients with malignant tumors, and these risk factors should be targeted for intervention to reduce the occurrence of oral mucositis.
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http://dx.doi.org/10.21037/apm-21-1675DOI Listing
July 2021

Multiplexing Methods for Simultaneous Large-Scale Transcriptomic Profiling of Samples at Single-Cell Resolution.

Adv Sci (Weinh) 2021 09 8;8(17):e2101229. Epub 2021 Jul 8.

Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.

Barcoding technology has greatly improved the throughput of cells and genes detected in single-cell RNA sequencing (scRNA-seq) studies. Recently, increasing studies have paid more attention to the use of this technology to increase the throughput of samples, as it has greatly reduced the processing time, technical batch effects, and library preparation costs, and lowered the per-sample cost. In this review, the various DNA-based barcoding methods for sample multiplexing are focused on, specifically, on the four major barcoding strategies. A detailed comparison of the barcoding methods is also presented, focusing on aspects such as sample/cell throughput and gene detection, and guidelines for choosing the most appropriate barcoding technique according to the personalized requirements are developed. Finally, the critical applications of sample multiplexing and technical challenges in combinatorial labeling, barcoding in vivo, and multimodal tagging at the spatially resolved resolution, as well as, the future prospects of multiplexed scRNA-seq, for example, prioritizing and predicting the severity of coronavirus disease 2019 (COVID-19) in patients of different gender and age are highlighted.
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http://dx.doi.org/10.1002/advs.202101229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425911PMC
September 2021

Outbreak of Acute Respiratory Illness Associated with Human Adenovirus Type 4 at the U.S. Coast Guard Academy, 2019.

J Infect Dis 2021 Jun 17. Epub 2021 Jun 17.

National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

Background: Although a human adenovirus (HAdV) vaccine is available for military use, officers-in-training are not routinely vaccinated. We describe an HAdV-associated respiratory outbreak among unvaccinated cadets at the U.S. Coast Guard Academy and its impact on cadet training.

Methods: We defined a case as a cadet with new onset cough or sore throat during August 1-October 4, 2019. We reviewed medical records and distributed a questionnaire to identify cases and to estimate impact on cadet training. We performed real-time PCR testing on patient and environmental samples and whole genome sequencing on a subset of positive patient samples.

Results: Among the 1,072 cadets, 378 (35%) cases were identified by medical records (n=230) or additionally by the questionnaire (n=148). Of the 230 cases identified from medical records, 138 (60%) were male and 226 (98%) had no underlying conditions. From questionnaire responses, 113/228 (50%) cases reported duty restrictions. Of cases with respiratory specimens, 36/50 (72%) were HAdV positive; all 14 sequenced specimens were HAdV-4a1. Sixteen (89%) of 18 environmental specimens from the cadet dormitory were HAdV-positive.

Conclusions: The HAdV-4-associated outbreak infected a substantial number of cadets and significantly impacted cadet training. Routine vaccination could prevent HAdV respiratory outbreaks in this population.
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http://dx.doi.org/10.1093/infdis/jiab322DOI Listing
June 2021

Predictive Value of Limb Artery Indices and Endothelial Functional Tests for the Degree of Coronary Artery Stenosis in a Diabetic Population.

Int J Gen Med 2021 3;14:2343-2349. Epub 2021 Jun 3.

Department of Integrative Cardiology, China-Japan Friendship Hospital, Beijing, People's Republic of China.

Objective: To investigate the correlation between limb artery indices (brachial-ankle pulse wave velocity and ankle-brachial index), endothelial function index (FMD value), and the degree of coronary artery stenosis in diabetic patients and analyze their values in predicting the degree of coronary artery stenosis.

Methods: The study included 151 patients with type 2 diabetes mellitus and suspected coronary atherosclerotic heart disease. The patients were divided into "coronary atherosclerotic heart disease" (N=94) and "non-coronary atherosclerotic heart disease" (N=57) groups based on the coronary angiographic findings. Within the coronary atherosclerotic heart disease group, the patients were further divided into "low stenosis" (N=47) and "high stenosis" (N=47) subgroups according to their Gensini score. Indicators such as brachial-ankle pulse wave velocity, ankle-brachial index, and FMD value were measured and correlated with the degree of coronary artery stenosis. Logistic regression models were constructed and receiver operating characteristic curves plotted to assess the predictive ability of limb artery and endothelial functional indices for the degree of coronary artery stenosis.

Results: In a diabetic population, FMD value (=0.003), ankle-brachial index (=0.004), and brachial-ankle pulse wave velocity (=0.003) were different in patients with and without coronary atherosclerotic heart disease. In the population with both diabetes mellitus and coronary atherosclerotic heart disease, the ankle-brachial index and FMD value were both independently associated with the degree of coronary artery stenosis (=0.003). The area under the receiver operating characteristic curve plotted from the combined coefficients of ankle-brachial index and FMD value was 0.773, which is predictive of coronary artery stenosis in diabetic patients.

Conclusion: Ankle-brachial index and FMD value are indicative of the degree of coronary artery stenosis in diabetic patients, and predictive efficacy can be improved by combining the two tests.
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http://dx.doi.org/10.2147/IJGM.S316297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184229PMC
June 2021

Neuroprotective effects of dropping pills in Parkinson's disease.

J Pharm Anal 2021 Apr 20;11(2):220-231. Epub 2020 Jun 20.

Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.

Parkinson's disease (PD) is the second most common neurodegenerative disease in the world; however, it lacks effective and safe treatments. dropping pill (GBDP), a unique Chinese leaf extract preparation, exhibits antioxidant and neuroprotective effects and has a potential as an alternative therapy for PD. Thus, the aims of this study were to evaluate the effects of GBDP in in vitro and in vivo PD models and to compare the chemical constituents and pharmacological activities of GBDP and the extract EGb 761. Using liquid chromatography tandem-mass spectrometry, 46 GBDP constituents were identified. Principal component analysis identified differences in the chemical profiles of GBDP and EGb 761. A quantitative analysis of 12 constituents showed that GBDP had higher levels of several flavonoids and terpene trilactones than EGb 761, whereas EGb 761 had higher levels of organic acids. Moreover, we found that GBDP prevented 6-hydroxydopamine-induced dopaminergic neuron loss in zebrafish and improved cognitive impairment and neuronal damage in methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced PD mice. Although similar effects were observed after EGb 761 treatment, the neuroprotective effects were greater after GBDP treatment on several endpoints. In addition, in vitro results suggested that the Akt/GSK3β pathway may be involved in the neuroprotective effects of GBDP. These findings demonstrated that GBDP have potential neuroprotective effects in the treatment of PD.
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http://dx.doi.org/10.1016/j.jpha.2020.06.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116202PMC
April 2021

Association of Myopia and Genetic Variants of and in the TGF-β Signaling Pathway: A Longitudinal Study in Chinese School-Aged Children.

Front Cell Dev Biol 2021 28;9:628182. Epub 2021 Apr 28.

Eye Hospital, Wenzhou Medical University, Wenzhou, China.

Background: Myopia is a complex multifactorial condition which involves several overlapping signaling pathways mediated by distinct genes. This prospective cohort study evaluated the associations of two genetic variants in the TGF-β signaling pathway with the onset and progression of myopia and ocular biometric parameters in Chinese school-aged children.

Methods: A total of 556 second grade children were examined and followed up for 3.5 years. Non-cycloplegic refraction and ocular biometric parameters were measured annually. Multivariate regression analysis was used to assess the effect of the rs10760673 and rs7550232 variants on the occurrence and progression of myopia. A 10,000 permutations test was used to correct for multiple testing. Functional annotation of single nucleotide polymorphisms (SNPs) was performed using RegulomeDB, HaploReg, and rVarBase.

Results: A total of 448 children were included in the analysis. After adjustments for gender, age, near work time and outdoor time with 10,000 permutations, the results indicated that the C allele and the AC or CC genotypes of rs7550232 adjacent to were associated with a significantly increased risk of the onset of myopia in two genetic models (additive: ' = 0.022; dominant: ' = 0.025). Additionally, the A allele and the AA or AG genotypes of rs10760673 of were associated with a significant myopic shift (additive: ' = 0.008; dominant: ' = 0.028; recessive: ' = 0.027). Furthermore, rs10760673 was associated with an increase in axial length (AL) (' = 0.013, β = 0.03) and a change in the ratio of AL to the corneal radius of curvature (AL/CRC) (' = 0.031, β = 0.003). Analysis using RegulomeDB, HaploReg, and rVarBase indicated that rs7550232 is likely to affect transcription factor binding, any motif, DNase footprint, and DNase peak.

Conclusion: The present study indicated that rs10760673 and rs7550232 may represent susceptibility loci for the progression and onset of myopia, respectively, in school-aged children. Associations of the variants of the and genes with myopia may be mediated by the TGF-β signaling pathway; this hypothesis requires validation in functional studies. This trial was registered as ChiCTR1900020584 at www.Chictr.org.cn.
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http://dx.doi.org/10.3389/fcell.2021.628182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115727PMC
April 2021

Genome-Wide DNA Methylation Alterations and Potential Risk Induced by Subacute and Subchronic Exposure to Food-Grade Nanosilica in Mice.

ACS Nano 2021 05 3;15(5):8225-8243. Epub 2021 May 3.

Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.

The intensive application of nanomaterials in the food industry has raised concerns about their potential risks to human health. However, limited data are available on the biological safety of nanomaterials in food, especially at the epigenetic level. This study examined the implications of two types of synthetic amorphous silica (SAS), food-grade precipitated silica (S200) and fumed silica Aerosil 200F (A200F), which are nanorange food additives. After 28-day continuous and intermittent subacute exposure to these SAS via diet, whole-genome methylation levels in mouse peripheral leukocytes and liver were significantly altered in a dose- and SAS type-dependent manner, with minimal toxicity detected by conventional toxicological assessments, especially at a human-relevant dose (HRD). The 84-day continuous subchronic exposure to all doses of S200 and A200F induced liver steatosis where S200 accumulated in the liver even at HRD. Genome-wide DNA methylation sequencing revealed that the differentially methylated regions induced by both SAS were mainly located in the intron, intergenic, and promoter regions after 84-day high-dose continuous exposure. Bioinformatics analysis of differentially methylated genes indicated that exposure to S200 or A200F may lead to lipid metabolism disorders and cancer development. Pathway validation experiments indicated both SAS types as potentially carcinogenic. While S200 inhibited the p53-mediated apoptotic pathway in mouse liver, A200F activated the HRAS-mediated MAPK signaling pathway, which is a key driver of hepatocarcinogenesis. Thus, caution must be paid to the risk of long-term exposure to food-grade SAS, and epigenetic parameters should be included as end points during the risk assessment of food-grade nanomaterials.
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http://dx.doi.org/10.1021/acsnano.0c07323DOI Listing
May 2021

LINC00184 Promotes Ovarian Cancer Cells Proliferation and Cisplatin Resistance by Elevating CNTN1 Expression via Sponging miR-1305.

Onco Targets Ther 2021 19;14:2711-2726. Epub 2021 Apr 19.

Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, People's Republic of China.

Objective: Cisplatin resistance is one of the main reasons for treatment failure in ovarian cancer (OC). Here, the effects of LINC00184 on cisplatin-resistant OC were studied.

Patients And Methods: LINC00184, miR-1305 and CNTN1 expression in tissues from 70 OC patients was determined by qRT-PCR, in situ hybridization and Western blot. OC cell lines and OC cisplatin-resistant cell lines were cultured. Cells were transfected using Lipofectamine 2000 and treated with 100 nM cisplatin. Cell proliferation and apoptosis were researched by the CCK-8 assay and flow cytometry. A dual-luciferase reporter gene assay and RNA pull-down were performed to explore the relationship between two genes. LINC00184, miR-1305 and CNTN1 expression in cells was detected by qRT-PCR and Western blot. An in vivo experiment was conducted using nude mice. Ki67 and CNTN1 expression and apoptosis of xenograft tumors were investigated using immunohistochemistry and a TUNEL assay.

Results: LINC00184 was up-regulated in OC clinical tissues and OC cells, especially in cisplatin-resistant OC patients and cells (<0.01 or <0.0001). LINC00184 overexpression significantly enhanced OC cell proliferation and cisplatin resistance, and inhibited OC cell apoptosis (<0.05 or <0.01). LINC00184 elevated CNTN1 expression via sponging miR-1305. LINC00184 overexpression markedly exacerbated the malignant phenotype of OC cells and cisplatin-resistant OC cells via the miR-1305/CNTN1 axis (<0.01). Silencing of LINC00184 significantly suppressed OC cell growth and cisplatin resistance in vivo (<0.01). LINC00184 silencing inhibited Ki67 and CNTN1 expression and promoted apoptosis of xenograft tumors. CNTN1 overexpression promoted proliferation and cisplatin resistance, and reduced apoptosis of OC cells (<0.05 or <0.01).

Conclusion: LINC00184 promoted OC cell proliferation and cisplatin resistance by elevating CNTN1 expression via sponging miR-1305.
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http://dx.doi.org/10.2147/OTT.S280490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064690PMC
April 2021

COVID-19 Quarantine Reveals That Behavioral Changes Have an Effect on Myopia Progression.

Ophthalmology 2021 Apr 14. Epub 2021 Apr 14.

School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, China; State Key Laboratory of Ophthalmology, Optometry and Visual Science, Wenzhou, China; National Clinical Research Center for Ocular Disease, Wenzhou, China. Electronic address:

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http://dx.doi.org/10.1016/j.ophtha.2021.04.001DOI Listing
April 2021

Enhanced throughput of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) real-time RT-PCR panel by assay multiplexing and specimen pooling.

J Virol Methods 2021 07 8;293:114149. Epub 2021 Apr 8.

Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.

A multiplex real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) assay for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was developed based on the same primer and probe sequences of an existing U.S. CDC Emergency Use authorized test panel, targeting SARS-CoV-2 N1, N2 and human RNase P genes in singleplex. Both singleplex and multiplex assays demonstrated linear dynamic ranges of 8 orders of magnitude and analytical limits of detection of 5 RNA transcript copies/reaction. Both assays showed 100 % agreement with 364 previously characterized clinical specimens (146 positive and 218 negative) for detection of SARS-CoV-2 RNA. To further increase testing throughput, 40 positive and 20 negative four-specimen pools were tested by the multiplex assay and showed 97.75 % and 100 % congruence with individual specimen tests, respectively. rRT-PCR assay multiplexing and sample pooling, individually or in combination, can substantially increase throughput of SARS-CoV-2 testing.
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http://dx.doi.org/10.1016/j.jviromet.2021.114149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8028606PMC
July 2021

Contribution of structural accessibility to the cooperative relationship of TF-lncRNA in myopia.

Brief Bioinform 2021 Sep;22(5)

School of Ophthalmology and Optometry and Eye Hospital, School of Biomedical Engineering at Wenzhou Medical University, Wenzhou 325027, P. R. China.

Transcriptional regulation is associated with complicated mechanisms including multiple molecular interactions and collaborative drive. Long noncoding RNAs (lncRNAs) have highly structured characteristics and play vital roles in the regulation of transcription in organisms. However, the specific contributions of conformation feature and underlying molecular mechanisms are still unclear. In the present paper, a hypothesis regarding molecular structure effect is presented, which proposes that lncRNAs fold into a complex spatial architecture and act as a skeleton to recruit transcription factors (TF) targeted binding, and which is involved in cooperative regulation. A candidate set of TF-lncRNA coregulation was constructed, and it was found that structural accessibility affected molecular binding force. In addition, transcription factor binding site (TFBS) regions of myopia-related lncRNA transcripts were disturbed, and it was discovered that base mutations affected the occurrence of significant molecular allosteric changes in important elements and variable splicing regions, mediating the onset and development of myopia. The results originated from structureomics and interactionomics and created conditions for systematic research on the mechanisms of structure-mediated TF-lncRNA coregulation in transcriptional regulation. Finally, these findings will help further the understanding of key regulatory roles of molecular allostery in cell physiological and pathological processes.
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http://dx.doi.org/10.1093/bib/bbab082DOI Listing
September 2021

Shedding of Culturable Virus, Seroconversion, and 6-Month Follow-up Antibody Responses in the First 14 Confirmed Cases of Coronavirus Disease 2019 in the United States.

J Infect Dis 2021 09;224(5):771-776

COVID-19 Response, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

We aimed to characterize presence of culturable virus in clinical specimens during acute illness, and antibody kinetics up to 6 months after symptom onset, among 14 early patients with coronavirus disease 2019 in the United States. We isolated viable severe acute respiratory syndrome coronavirus 2 from real-time reverse-transcription polymerase chain reaction-positive respiratory specimens collected during days 0-8 after onset, but not after. All 13 patients with 2 or more serum specimens developed anti-spike antibodies; 12 developed detectable neutralizing antibodies. We did not isolate virus after detection of neutralizing antibodies. Eight participants provided serum at 6 months after onset; all retained detectable anti-spike immunoglobulin G, and half had detectable neutralizing antibodies. Two participants reported not feeling fully recovered at 6 months.
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http://dx.doi.org/10.1093/infdis/jiab125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989348PMC
September 2021

Ligand Architecture Perturbation Influences the Reactivity of Nonheme Iron(V)-Oxo Tetraamido Macrocyclic Ligand Complexes: A Combined Experimental and Theoretical Study.

Inorg Chem 2021 Mar 1;60(6):4058-4067. Epub 2021 Mar 1.

Department of Chemistry and Nano Science, Ewha Womans University, Seoul 03760, Korea.

Iron(V)-oxo complexes bearing negatively charged tetraamido macrocyclic ligands (TAMLs) have provided excellent opportunities to investigate the chemical properties and the mechanisms of oxidation reactions of mononuclear nonheme iron(V)-oxo intermediates. Herein, we report the differences in chemical properties and reactivities of two iron(V)-oxo TAML complexes differing by modification on the "Head" part of the TAML framework; one has a phenyl group at the "Head" part (), whereas the other has four methyl groups replacing the phenyl ring (). The reactivities of and in both C-H bond activation reactions, such as hydrogen atom transfer (HAT) of 1,4-cyclohexadiene, and oxygen atom transfer (OAT) reactions, such as the oxidation of thioanisole and its derivatives, were compared experimentally. Under identical reaction conditions, showed much greater reactivity than , such as a 10-fold decrease in HAT and a 10-fold decrease in OAT by replacing the phenyl group (i.e., ) with four methyl groups (i.e., ). Then, density functional theory calculations were performed to rationalize the reactivity differences between and . Computations reproduced the experimental findings well and revealed that the replacement of the phenyl group in with four methyl groups in not only increased the steric hindrance but also enlarged the energy gap between the electron-donating orbital and the electron-accepting orbital. These two factors, steric hindrance and the orbital energy gap, resulted in differences in the reduction potentials of and and their reactivities in oxidation reactions.
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http://dx.doi.org/10.1021/acs.inorgchem.1c00110DOI Listing
March 2021

Performance of Oropharyngeal Swab Testing Compared With Nasopharyngeal Swab Testing for Diagnosis of Coronavirus Disease 2019-United States, January 2020-February 2020.

Clin Infect Dis 2021 02;72(3):403-410

Centers for Disease Control and Prevention, COVID-19 Response Team, Atlanta, Georgia, USA.

Among 146 nasopharyngeal (NP) and oropharyngeal (OP) swab pairs collected ≤7 days after illness onset, Real-Time Reverse Transcriptase Polymerase Chain Reaction assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 RT-PCR) diagnostic results were 95.2% concordant. However, NP swab cycle threshold values were lower (indicating more virus) in 66.7% of concordant-positive pairs, suggesting NP swabs may more accurately detect the amount of SARS-CoV-2.
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http://dx.doi.org/10.1093/cid/ciaa759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337670PMC
February 2021

Circular RNA circSEC24A Promotes Cutaneous Squamous Cell Carcinoma Progression by Regulating miR-1193/MAP3K9 Axis.

Onco Targets Ther 2021 22;14:653-666. Epub 2021 Jan 22.

Department of Dermatological, Xinxiang Central Hospital, Xinxiang City, Henan Province, People's Republic of China.

Background: Circular RNAs (circRNAs) have been increasingly demonstrated to play critical roles in cancer progression. However, the biological functions and underlying mechanism of circRNA SEC24 homolog A, COPII coat complex component (circSEC24A) in cutaneous squamous cell carcinoma (CSCC) have not been well elucidated yet.

Methods: The expression levels of circSEC24A, microRNA-1193 (miR-1193) and mitogen-activated protein kinase kinase kinase 9 (MAP3K9) were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and colony formation assay were used to assess cell proliferation ability. Flow cytometry and transwell assay were utilized to detect cell apoptosis and migration and invasion. Glycolytic metabolism was examined via the measurement of lactate production, glucose consumption, extracellular acidification rate (ECAR), hexokinase 2 (HK2) and Lactate dehydrogenase A (LDHA) expression. The interaction between miR-1193 and circSEC24A or MAP3K9 was predicted by starBase v2.0 and verified by dual-luciferase reporter, RNA Immunoprecipitation (RIP) and pull-down assay assays. The mice xenograft model was established to investigate the roles of circSEC24A in vivo.

Results: CircSEC24A and MAP3K9 were upregulated and miR-1193 was downregulated in CSCC tissues and cells. CircSEC24A knockdown inhibited the progression of CSCC cells by inhibiting cell proliferation, migration, invasion, and glycolysis and inducing apoptosis. Moreover, miR-1193 was a direct target of circSEC24A and its downregulation reversed the inhibitory effect of circSEC24A knockdown on the progression of CSCC cells. Furthermore, MAP3K9 was a downstream target of miR-1193 and its upregulation attenuated the anti-cancer role of miR-1193 in CSCC cells. Additionally, circSEC24A acted as a molecular sponge of miR-1193 to regulate MAP3K9 expression. Furthermore, interference of circSEC24A repressed tumor growth via upregulating miR-1193 and downregulating MAP3K9.

Conclusion: CircSEC24A interference suppressed the progression of CSCC by regulating miR-1193/MAP3K9 axis, which might be a promising strategy for CSCC treatment.
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http://dx.doi.org/10.2147/OTT.S275691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837553PMC
January 2021

Reduning injection and its effective constituent luteoloside protect against sepsis partly via inhibition of HMGB1/TLR4/NF-κB/MAPKs signaling pathways.

J Ethnopharmacol 2021 Apr 7;270:113783. Epub 2021 Jan 7.

Pharmaceutical Informatics Institute, College of Pharmaceutical Science, Zhejiang University, Hangzhou, 310058, China; State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China. Electronic address:

Ethnopharmacological Relevance: Reduning injection (RDN), a popular traditional Chinese medicine, formulated by three herbs (i.e., Artemisia carvifolia Buch.-Ham. ex Roxb., Lonicera japonica Thunb., and Gardenia jasminoides J. Ellis), has been widely used to treat upper respiratory infectious diseases in China.

Aim Of The Study: To investigate the protective effect of RDN on both lipopolysaccharides (LPS)- and cecal ligation and puncture (CLP)-induced septic mice. To identify the potentially effective constituent, and to determine its protective effect and underlying mechanism in vivo and in vitro.

Materials And Methods: Male C57BL/6 mice were used to establish septic model by tail intravenous injection of 4 mg/kg LPS or CLP surgery. After modeling, mice were administered by tail intravenous injection of RDN in the dose of 16 or 8 mL/kg/day. The mortality, histopathology, plasma levels of inflammatory cytokines were evaluated respectively. In addition, we screened the potentially effective substances of RDN against sepsis by detecting the nitric oxide (NO) production in LPS-stimulated Raw 264.7 cells and verified the effect of luteoloside in CLP-induced septic mice subsequently. Finally, the underlying mechanisms of RDN and luteoloside were investigated in the inflammatory model in vitro.

Results: Administration of RDN significantly reduced the mortality and increased the survival rate in both LPS- and CLP-induced septic mice. Meanwhile, RDN reduced the release of inflammatory cytokines accompanied by alleviating the organs damage of lung, liver, and kidney in CLP-induced septic mice. Moreover, several components from Gardenia jasminoides J. Ellis extract (ZZ) or Lonicera japonica Thunb and Artemisia carvifolia Buch.-Ham. ex Roxb extract (JQ) as well as the constituents of luteoloside, quercetin, and caffeic acid were screened out to have obvious anti-inflammatory activity, which may be the potentially effective substances of RDN against sepsis. We further verified the protective role of luteoloside in CLP-induced septic mice. In addition, RDN and luteoloside significantly inhibited both the secretion and translocation of mobility group box (HMGB)1, and HMGB1-mediated activation of TLR4/NF-κB/MAPKs signaling pathways.

Conclusion: RDN and its effective constituent luteoloside exhibited a significant protective effect against sepsis, which were potential candidate drugs for treatment of sepsis. The mechanism of antisepsis partly was related to inhibition of HMGB1/TLR4/NF-κB/MAPKs signaling pathways. The results provide an evidence base for the follow-up clinical application of RDN in treatment of sepsis.
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http://dx.doi.org/10.1016/j.jep.2021.113783DOI Listing
April 2021

Catalytic Four-Electron Reduction of Dioxygen by Ferrocene Derivatives with a Nonheme Iron(III) TAML Complex.

Inorg Chem 2020 Dec 10;59(24):18010-18017. Epub 2020 Dec 10.

Department of Chemistry and Nano Science, Ewha Womans University, Seoul 03760, Korea.

A mononuclear nonheme iron(III) complex with a tetraamido macrocyclic ligand (TAML), [(TAML)Fe] (), is a selective precatalyst for four-electron reduction of dioxygen by ferrocene derivatives in the presence of acetic acid (CHCOOH) in acetone. This is the first work to show that a nonheme iron(III) complex catalyzes the four-electron reduction of O by one-electron reductants. An iron(V)-oxo complex, [(TAML)Fe(O)] (), was produced by oxygenation of with O via the formation of triacetone triperoxide (TATP), acting as an autocatalyst that shortened the induction time for the generation of . Decamethylferrocene (MeFc) and octamethylferrocene (MeFc) reduced to by two electrons in the presence of CHCOOH to produce decamethylferrocenium cation (MeFc) and octamethylferrocenium cation (MeFc), respectively. Then, was oxygenated by O to regenerate via the formation of TATP. In the cases of ferrocene (Fc), bromoferrocene (BrFc) and 1,1'-dibromoferrocene (BrFc), initial electron transfer from ferrocene derivatives to occurred; however, neither a second proton-coupled electron transfer from ferrocene derivatives to nor a catalytic four-electron reduction of O occurred.
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http://dx.doi.org/10.1021/acs.inorgchem.0c02400DOI Listing
December 2020

Protective effects of Ginkgo Biloba Dropping Pills against liver ischemia/reperfusion injury in mice.

Chin Med 2020 Nov 19;15(1):122. Epub 2020 Nov 19.

Pharmaceutical informatics institute, College of Pharmaceutical Science, Zhejiang University, 310058, Hangzhou, China.

Background: Liver ischemia/reperfusion (I/R) injury is an inevitable pathological phenomenon in various clinical conditions, such as liver transplantation, resection surgery, or shock, which is the major cause of morbidity and mortality after operation. Ginkgo Biloba Dropping Pill (GBDP) is a unique Chinese Ginkgo Biloba leaf extract preparation that exhibits a variety of beneficial biological activities. The aim of this study is to investigate the protective effects of GBDP on the liver I/R injury both in the in vitro and in vivo.

Methods: Hypoxia/reoxygenation (H/R) experiments were performed in alpha mouse liver 12 (AML-12) cells and primary hepatocytes, which were pretreated with GBDP (60 or 120 µg/mL) followed by incubation in a hypoxia chamber. Cell viability was detected by 3-(4,5-dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide (MTT) assay. Annexin V staining as well as western blot analysis of apoptosis-related proteins was performed to detect the protective effect of GBDP on cell apoptosis induced by H/R injury. C57BL/6 mice were used to establish the liver I/R injury model, and were pretreated with GBDP (100 or 200 mg/kg/day, i.g.) for two weeks. The liver damage was evaluated by detection of plasma levels of alanine transaminase (ALT) and aspartate transaminase (AST), as well as histopathological examinations. Liver inflammation was determined by detecting the secretion of pro-inflammatory cytokines and neutrophil infiltration through enzyme-linked immunosorbent assay (ELISA) and myeloperoxidase (MPO) immunohistochemistry staining. Finally, Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick and labeling (TUNEL) staining and western blot analysis of apoptosis-related proteins were used to investigate the anti-apoptotic effect of GBDP in mice.

Results: In the in vitro study, GBDP pretreatment improved the cell viability of AML-12 cells in the H/R injury model. Similarly, the same result was found in the primary hepatocytes isolated from C57BL/6 mice. Moreover, GBDP decreased the number of apoptotic cells and reduced the expression of apoptosis-related proteins induced by H/R injury. In the in vivo study, oral administration of GBDP ameliorated liver injury evidenced by a significant decline in the levels of ALT and AST. Furthermore, the result of hematoxylin and eosin (H&E) staining showed that GBDP reduced the size of necrosis area in the liver tissue. In addition, the decreased infiltration of neutrophils and secretion of pro-inflammatory cytokines indicated that GBDP may play an anti-inflammatory effect. More importantly, GBDP reduced TUNEL-positive cells and the expression of apoptosis-related proteins in the liver indicating GBDP has anti-apoptotic effects.

Conclusions: Our findings elucidated that GBDP has potential effects for protecting against liver I/R injury characterized by its anti-apoptotic, anti-necrotic, and anti-inflammatory properties, which would promisingly make contributions to the exploration of therapeutic strategies in the liver I/R injury.
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http://dx.doi.org/10.1186/s13020-020-00404-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678318PMC
November 2020

A Clinical Genomics-Guided Prioritizing Strategy Enables Selecting Proper Cancer Cell Lines for Biomedical Research.

iScience 2020 Nov 28;23(11):101748. Epub 2020 Oct 28.

Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.

Selecting appropriate cell lines to represent a disease is crucial for the success of biomedical research, because the usage of less relevant cell lines could deliver misleading results. However, systematic guidance on cell line selection is unavailable. Here we developed a clinical Genomics-guided Prioritizing Strategy for Cancer Cell Lines (CCL-cGPS) and help to guide this process. Statistical analyses revealed CCL-cGPS selected cell lines were among the most appropriate models. Moreover, we observed a linear correlation between the drug response and CCL-cGPS score of cell lines for breast and thyroid cancers. Using RT4 cells selected by CCL-GPS, we identified mebendazole and digitoxin as candidate drugs against bladder cancer and validate their promising anticancer effect through and experiments. Additionally, a web tool was developed. In conclusion, CCL-cGPS bridges the gap between tumors and cell lines, presenting a helpful guide to select the most suitable cell line models.
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http://dx.doi.org/10.1016/j.isci.2020.101748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662851PMC
November 2020

CellTalkDB: a manually curated database of ligand-receptor interactions in humans and mice.

Brief Bioinform 2021 Jul;22(4)

College of Pharmaceutical Sciences at Zhejiang University, China.

Cell-cell communications in multicellular organisms generally involve secreted ligand-receptor (LR) interactions, which is vital for various biological phenomena. Recent advancements in single-cell RNA sequencing (scRNA-seq) have effectively resolved cellular phenotypic heterogeneity and the cell-type composition of complex tissues, facilitating the systematic investigation of cell-cell communications at single-cell resolution. However, assessment of chemical-signal-dependent cell-cell communication through scRNA-seq relies heavily on prior knowledge of LR interaction pairs. We constructed CellTalkDB (http://tcm.zju.edu.cn/celltalkdb), a manually curated comprehensive database of LR interaction pairs in humans and mice comprising 3398 human LR pairs and 2033 mouse LR pairs, through text mining and manual verification of known protein-protein interactions using the STRING database, with literature-supported evidence for each pair. Compared with SingleCellSignalR, the largest LR-pair resource, CellTalkDB includes not only 2033 mouse LR pairs but also 377 additional human LR pairs. In conclusion, the data on human and mouse LR pairs contained in CellTalkDB could help to further the inference and understanding of the LR-interaction-based cell-cell communications, which might provide new insights into the mechanism underlying biological processes.
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http://dx.doi.org/10.1093/bib/bbaa269DOI Listing
July 2021

Chemical constituents of Panax ginseng and Panax notoginseng explain why they differ in therapeutic efficacy.

Pharmacol Res 2020 11 27;161:105263. Epub 2020 Oct 27.

State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address:

Panax ginseng (Meyer) and Panax notoginseng (Burkill), belonging to the family Araliaceae, are used worldwide as medicinal and functional herbs. Numerous publications over the past decades have revealed that both P. notoginseng and P. ginseng contain important bioactive ingredients such as ginsenosides and exert multiple pharmacological effects on nervous system and immune diseases. However, based on traditional Chinese medicine (TCM) theory, their applications clearly differ as ginseng reinforces vital energy and notoginseng promotes blood circulation. In this article, we review the similarities and differences between ginseng and notoginseng in terms of their chemical composition and pharmacological effects. Their chemical comparisons indicate that ginseng contains more polysaccharides and amino acids, while notoginseng has more saponins, volatile oil, and polyacetylenes. Regarding pharmacological effects, ginseng exhibits better protective effects on cardiovascular disease, nerve disease, cancer, and diabetes mellitus, whereas notoginseng displays a superior protective effect on cerebrovascular disease. The evidence presented in this review facilitates further research and clinical applications of these two herbs, and exploration of the relationship between the chemical components and disease efficacy may be the critical next step.
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http://dx.doi.org/10.1016/j.phrs.2020.105263DOI Listing
November 2020

Pneumococcal vaccine coverage among individuals aged 18 to 64 years old with underlying medical conditions in the UK: a retrospective database analysis.

BMC Public Health 2020 Oct 21;20(1):1584. Epub 2020 Oct 21.

Imperial College London, London, UK.

Background: In the UK certain groups with pre-disposing conditions are eligible for vaccination with the pneumococcal polysaccharide vaccine (PPV23). Uptake of the vaccine in these individuals has not been reported for 10 years. Hence this study investigated the rates of pneumococcal vaccination, the time to vaccination since diagnosis, and factors associated with vaccination in individuals aged 18-64 years with certain underlying medical conditions.

Methods: A retrospective database analysis was conducted using the Clinical Practice Research Datalink (CPRD). Individuals aged 18 to 64 years who had a diagnosis for underlying medical conditions of interest at the index date (January 1, 2011 to December 31, 2015) were included in this study. Both underlying conditions and pneumococcal vaccination were identified using Read codes. A multivariable logistic regression model was used to identify factors associated with pneumococcal vaccination.

Results: A total of 99,153 individuals with underlying medical conditions were included in this study. Within 1 year of follow-up, 13.6% had received pneumococcal vaccination. This figure rose to 32.0% after 4 years of follow-up. The mean time between diagnosis and vaccination was 148.7 days across the overall cohort. Based on multivariate analysis of results, individuals with chronic heart disease, chronic kidney disease, chronic liver disease, chronic respiratory disease or diabetes mellitus were significantly less likely (P < 0.0001) to be vaccinated than those with immunosuppression. Individuals were significantly more likely to receive a pneumococcal vaccination if they received an influenza vaccination in the first year of follow-up than those who did not (P < 0.001).

Conclusions: Despite the Joint Committee on Vaccination and Immunisation (JCVI) recommendations for pneumococcal vaccination in clinical risk groups, rates of pneumococcal vaccination are suboptimal in the UK for individuals aged 18-64 with underlying medical conditions. Further emphasis should be made on the importance of increased pneumococcal vaccination coverage in the UK, given the increased risk of morbidity and mortality associated with indicative underlying medical conditions.
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http://dx.doi.org/10.1186/s12889-020-09613-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7579959PMC
October 2020

Integrative network analysis identifies an immune-based prognostic signature as the determinant for the mesenchymal subtype in epithelial ovarian cancer.

Medicine (Baltimore) 2020 Oct;99(41):e22549

Molecular Laboratory, Beilun People's Hospital, Ningbo, China.

Background: Epithelial ovarian cancer (EOC) has been classified into four molecular subtypes, of which the mesenchymal subtype has the poorest survival. Our goal is to develop an immune-based prognostic signature by incorporating molecular subtypes for EOC patients.

Methods: The gene expression profiles of EOC samples were collected from seven public datasets as well as an internal retrospective validation cohort, containing 1192 EOC patients. Network analysis was applied to integrate the mesenchymal modalities and immune signature to establish an immune-based prognostic signature for EOC (IPSEOC). The signature was trained and validated in eight independent datasets.

Results: Seven immune genes were identified as key regulators of the mesenchymal subtype and were used to construct the IPSEOC. The IPSEOC significantly divided patients into high- and low-risk groups in discovery (OS: P < .0001), 6 independent public validation sets (OS: P = .04 to P = .002), and an internal retrospective validation cohort (OS: P = .025). Furthermore, pathway analysis revealed that differences between risk groups were mainly activation of mesenchymal-related signalling. Moreover, a significant correlation existed between the IPSEOC values versus clinical phenotypes including late tumor stages, drug resistance.

Conclusion: We propose an immune-based signature, which is a promising prognostic biomarker in ovarian cancer. Prospective studies are needed to further validate its analytical accuracy and test the clinical utility.
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http://dx.doi.org/10.1097/MD.0000000000022549DOI Listing
October 2020

Long non-coding RNA PICSAR knockdown inhibits the progression of cutaneous squamous cell carcinoma by regulating miR-125b/YAP1 axis.

Life Sci 2021 Jun 22;274:118303. Epub 2020 Aug 22.

Department of Dermatology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. Electronic address:

Aims: The purpose of this study was to explore the precise role and mechanism of p38 inhibiting cutaneous squamous cell carcinoma associated lincRNA (PICSAR) in CSCC.

Materials And Methods: The expression levels of PICSAR, microRNA-125b (miR-125b) and yes-associated protein1 (YAP1) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation, apoptosis and invasion were evaluated by Cell Counting Kit-8 (CCK-8) assay, flow cytometry, transwell assay, respectively. The interaction between miR-125b and PICSAR or YAP1 was predicted by bioinformatics software and confirmed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Western blot was employed to detect the protein expression of YAP1. The mice xenograft model was established to investigate the role of PICSAR in vivo.

Key Findings: PICSAR was upregulated in CSCC tissues and cells. PICSAR knockdown inhibited cell proliferation and invasion and induced apoptosis in CSCC cells. Moreover, miR-125b could directly bind to PICSAR and its inhibition reversed the effect of PICSAR knockdown on proliferation, invasion and apoptosis in CSCC cells. In addition, YAP1 was a direct target of miR-125b and its overexpression attenuated the anti-cancer role of miR-125b in CSCC cells. Furthermore, YAP1 expression was positively regulated by PICSAR and negatively regulated by miR-125b. Besides, interference of PICSAR suppressed tumor growth by upregulating miR-125b and downregulating YAP1.

Significance: PICSAR knockdown suppressed cell proliferation and invasion and promoted apoptosis in CSCC cells by regulating miR-125b/YAP1 axis, providing new sights for treatment of CSCC.
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http://dx.doi.org/10.1016/j.lfs.2020.118303DOI Listing
June 2021
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