Publications by authors named "Yanqing Wang"

237 Publications

Impact of H-Type Hypertension on Intraplaque Neovascularization Assessed by Contrast-Enhanced Ultrasound.

J Atheroscler Thromb 2021 Apr 8. Epub 2021 Apr 8.

Ultrasound Medical Center, Lanzhou University Second Hospital.

Aim: H-type hypertension is connected with carotid atherosclerotic plaques and stroke, whereas neovascularization is a dominant contributor to plaque vulnerability. However, the correlation between H-type hypertension and plaque vulnerability remains unclear. This study aims to explore the influence of H-type hypertension on intraplaque neovascularization (IPN).

Methods: We enrolled 235 patients with carotid plaques into the investigation and classified them into four groups: H-type hypertension group, simple hypertension group, isolated hyperhomocysteinemia group, and control group. Contrast-enhanced ultrasound (CEUS) was performed on them and IPN was evaluated using semi-quantitative visual grading: grade 1 (no microbubbles or microbubbles limited to the adventitial side and/or shoulder of plaque) and, grade 2 (diffused microbubbles within plaque or microbubbles enter plaque core). To analyze the correlation between H-type hypertension and the degree of plaque enhancement, logistic regression was used.

Results: Compared with those with CEUS grade 1 plaques, those with CEUS grade 2 plaques had higher frequency of ischemic stroke (29.0% vs. 45.1%, P<0.05), hypertension (41.0% vs. 56.3%, P<0.05), and H-type hypertension (18.0% vs. 29.6%, P<0.05). No significant differences existed in plaque morphology, plaque echogenicity, and the severity of carotid artery stenosis between the degree of plaque enhancement (all P >0.05). H-type hypertension (multivariate-adjusted OR: 3.036, 95% CI: 1.258-7.329) was independently connected with the degree of plaque enhancement even after adjusting for other covariates.

Conclusion: H-type hypertension is expressly connected with the degree of plaque enhancement and may facilitate plaque vulnerability. Our findings may offer a new insight for treating vulnerable plaque, lowering blood pressure, and lowering homocysteine equally crucial.
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http://dx.doi.org/10.5551/jat.61275DOI Listing
April 2021

[Design of Gas Detection System Based on STM32 Infusion Set].

Zhongguo Yi Liao Qi Xie Za Zhi 2021 Apr;45(2):159-162

Nanchang University, Nanchang, 330031.

Aiming at the low efficiency and low quality detection level of the manual infusion set, a gas detection system for infusion set based on STM32 single-chip microcomputer was designed. The detection system includes hardware system design and software system design. The hardware system is based on the STM32F103 single-chip microcomputer. It mainly designs the gas pressure sensor acquisition circuit and the multi-way solenoid valve control circuit. The software system uses a C ++ real-time operating system to ensure system monitoring's real-time performance and validity. Test data is transmitted to the upper computer and displayed via USB serial communication. The experiment proves that the infusion set gas detection system can perform gas detection on the infusion set. The system has the characteristics of stability and high accuracy. The relative error of the experimental measurement is within ±5%, and the detection efficiency is better than manual detection.
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http://dx.doi.org/10.3969/j.issn.1671-7104.2021.02.008DOI Listing
April 2021

5-Substituted isatin thiosemicarbazones as inhibitors of tyrosinase: Insights of substituent effects.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Jul 9;255:119669. Epub 2021 Mar 9.

College of Chemistry and Environmental Engineering, Institute of Environmental Toxicology and Environmental Ecology, Yancheng Teachers University, Xiwang Avenue South Rd. 2, Yancheng 224007, PR China. Electronic address:

Seven isatin-thiosemicarbazone analogues bearing different substituents (R) attached at C-5 of the indoline ring, TSC-ISA-R (R = -H, -CH, -OCH, -OCF, -F, -Cl and -NO), were synthesized and evaluated as inhibitors of mushroom tyrosinase (TYR). The inhibitory behaviour and performance of TSC-ISA-R were investigated spectroscopically in relation to the substituent modifications through examining their inhibition against the diphenolase activity of TYR using L-DOPA as a substrate. The IC values of TSC-ISA-R were determined to be in the range of 81-209 μM. The kinetic analysis showed that TSC-ISA-R were reversible and mixed type inhibitors. Three potential non-covalent interactions rather than complexation including the binding of TSC-ISA-R with free TYR, TYR-L-DOPA complex, and with substrate L-DOPA were found to be involved in the inhibition. The substituent modifications affected these interactions by varying the characters of the resulting TSC-ISA-R in different degrees. The thiosemicarbazido moiety of each TSC-ISA-R contributed predominantly to the inhibition, and the isatin moiety seemed to play a regulatory role in the binding of TSC-ISA-R to the target molecules. The results of theoretical calculations using density functional theory method indicated a different effect of -R on the electron distribution in HOMO of TSC-ISA-R. The LUMO-HOMO energy gap of TSC-ISA-R almost accords with the trend of their experimental inhibition potency.
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http://dx.doi.org/10.1016/j.saa.2021.119669DOI Listing
July 2021

Silencing of lncRNA UCA1 inhibited the pathological progression in PCOS mice through the regulation of PI3K/AKT signaling pathway.

J Ovarian Res 2021 Mar 20;14(1):48. Epub 2021 Mar 20.

Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, China.

Background: Polycystic ovary syndrome (PCOS) is the most common hormonal disorder among reproductive-aged women worldwide, however, the mechanisms and progression of PCOS still unclear due to its heterogeneous nature. Using the human granulosa-like tumor cell line (KGN) and PCOS mice model, we explored the function of lncRNA UCA1 in the pathological progression of PCOS.

Results: CCK8 assay and Flow cytometry were used to do the cell cycle, apoptosis and proliferation analysis, the results showed that UCA1 knockdown in KGN cells inhibited cell proliferation by blocking cell cycle progression and promoted cell apoptosis. In the in vivo experiment, the ovary of PCOS mice was injected with lentivirus carrying sh-UCA1, the results showed that knockdown of lncRNA UCA1 attenuated the ovary structural damage, increased the number of granular cells, inhibited serum insulin and testosterone release, and reduced the pro-inflammatory cytokine production. Western blot also revealed that UCA1 knockdown in PCOS mice repressed AKT activation, inhibitor experiment demonstrated that suppression of AKT signaling pathway, inhibited the cell proliferation and promoted apoptosis.

Conclusions: Our study revealed that, in vitro, UCA1 knockdown influenced the apoptosis and proliferation of KGN cells, in vivo, silencing of UCA1 regulated the ovary structural damage, serum insulin release, pro-inflammatory production, and AKT signaling pathway activation, suggesting lncRNA UCA1 plays an important role in the pathological progression of PCOS.
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http://dx.doi.org/10.1186/s13048-021-00792-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7980617PMC
March 2021

INO80 participates in the pathogenesis of recurrent miscarriage by epigenetically regulating trophoblast migration and invasion.

J Cell Mol Med 2021 Apr 16;25(8):3885-3897. Epub 2021 Mar 16.

Department of Gynecology and Obstetrics, Renmin Hospital of Wuhan University, Wuhan, China.

The INO80 complex, a SWI/SNF family chromatin remodeler, has regulatory effects on ESC self-renewal, somatic cell reprogramming and blastocyst development. However, the role of INO80 in regulating trophoblast cells and recurrent miscarriage (RM) remains elusive. To investigate the in vivo effects of Ino80 in embryo development, we disrupted Ino80 in C57 mice, which resulted in embryonic lethality. Silencing of Ino80 led to decreased survival capacity, migration and invasion of trophoblasts. Furthermore, RNA high-throughput sequencing (RNA-seq) revealed that Ino80 silencing closely resembled the gene expression changes in RM tissues. To investigate the mechanisms for these results, RNA-seq combined with high-throughput sequencing (ChIP-seq) was used in trophoblast cells, and it showed that Ino80 physically occupies promoter regions to affect the expression of invasion-associated genes. Last, Western blotting analyses and immunofluorescence staining revealed that the content of INO80 was reduced in RM patients compared to in healthy controls. This study indicates that INO80 has a specific regulatory effect on the viability, migration and invasion of trophoblast cells. Combined with its regulation of the expression of invasion-associated genes, it has been proposed that epigenetic regulation plays an important role in the occurrence of RM, potentially informing RM therapeutic strategies.
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http://dx.doi.org/10.1111/jcmm.16322DOI Listing
April 2021

Self-Reported Fatigue in Chinese Children and Adolescents During Cancer Treatment.

J Pediatr Oncol Nurs 2021 Mar 9:1043454221992304. Epub 2021 Mar 9.

School of Nursing, 12478Fudan University, Shanghai, China.

: Fatigue is a prevalent and distressing symptom in children and adolescents with cancer. : This study aimed to (1) investigate the current fatigue status reported by Chinese children and adolescents with cancer during active cancer treatment and (2) examine whether sociodemographic information, disease and treatment information, co-occurring symptoms, function and related clinical data are significantly associated with fatigue according to the biopsychosocial model. : Participants were children aged 8-17 years, who had undergone treatment for cancer at four hospitals in China. Children completed the Chinese version of the Pediatric Patient-Reported Outcomes Measurement Information System short forms. : In total, 187 children (33.16% female, mean age 10.28 years) participated. The mean T-score for child-reported fatigue was 48.52 (34-72). Multiple linear regression analysis showed that fatigue in pediatric active cancer treatment could be significantly predicted by greater child-reported pain interference (= 0.391, < .001), greater depressive symptoms (= 0.443, < .001), and reduced mobility (= -0.226, = .004) (adjusted  = 0.613, = 16.476, < .001). : Children and adolescents with cancer experience multiple, intersecting troubling symptoms during their treatment. There is a need to attend to the biopsychosocial aspects of care for children and adolescents during active cancer treatment. To reduce pediatric oncology patients' fatigue level, clinicians could develop culturally sensitive interventions to alleviate children's pain interference, treat depressive symptoms, and maximize their physical mobility.
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http://dx.doi.org/10.1177/1043454221992304DOI Listing
March 2021

Prenatal Exposure to Retrorsine Induces Developmental Toxicity and Hepatotoxicity of Fetal Rats in a Sex-Dependent Manner: The Role of Pregnane X Receptor Activation.

J Agric Food Chem 2021 Mar 8;69(10):3219-3231. Epub 2021 Mar 8.

Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan, 430071 Hubei Province, China.

Pyrrolizidine alkaloids (PAs) are a type of natural phytotoxin that contaminate food and feed and become an environmental health risk to humans and livestock. PAs exert toxicity that requires metabolic activation by cytochrome P450 (CYP) 3A, and case reports showed that fetuses are quite susceptible to PAs toxicity. The aim of this study was to explore the characteristics of developmental toxicity and fetal hepatotoxicity induced by retrorsine (RTS, a typcial toxic PA) and the underlying mechanism. Pregnant Wistar rats were intragastrically administered with 20 mg/(kg·day) RTS from gestation day (GD) 9 to 20. Results showed that prenatal RTS exposure lowered fetal bodyweights, reduced hepatocyte numbers, and potentiated hepatic apoptosis in fetuses, particularly females. Simutaneously, RTS increased CYP3A expression and pregnane X receptor (PXR) activation in female fetal liver. We further confirmed that RTS was a PXR agonist in LO2 and HepG2 cell lines. Furthermore, agonism or antagonism of androgen receptor (AR) either induced or blocked RTS-mediated PXR activation, respectively. As a PXR agonist, RTS toxicity was exacerbated in female fetus due to the increased CYP3A induction and self-metabolism, while the inhibitory effect of AR on PXR activation reduced the susceptibility of male fetus to RTS. Our findings indicated that PXR may be a potential therapeutic target for PA toxicity.
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http://dx.doi.org/10.1021/acs.jafc.0c06748DOI Listing
March 2021

Platinum (II)-coordinated Portulaca oleracea polysaccharides as metal-drug based polymers for anticancer study.

Colloids Surf B Biointerfaces 2021 May 18;201:111628. Epub 2021 Feb 18.

Institute of Environmental Toxicology and Environmental Ecology, Yancheng Teachers University, Yancheng City, Jiangsu Province, 224051, People's Republic of China. Electronic address:

Novel polysaccharide-platinum conjugated polymers bearing alendronate on Portulaca oleracea polysaccharides (PPS) were designed and synthesized. Their chemical structures and properties were characterized by Fourier transform infrared spectroscopy (FT-IR), H NMR and P NMR spectroscopy, Thermogravimetric analysis (TGA), X-ray powder diffraction (XRD), UV-vis spectrophotometer (UV-vis) and other analysis methods. The results demonstrated that alendronate can be used as the linker of Portulaca oleracea polysaccharides and platinum compounds. Portulaca oleracea polysaccharides-alendronate (PPS-ALN) conjugates exhibited stronger antioxidant ability than PPS. The cytotoxicity assay to cancer cells was tested in vitro, and the Portulaca oleracea polysaccharides-alendronate-platinum (PPS-ALN-Pt) conjugates strongly inhibited the proliferation of cancer cells than PPS and PPS-ALN. The evaluation of complexes affinity toward supercoiled plasmid DNA, displayed a high DNA interaction. Interestingly, the platinum conjugates displayed immunological competence in HeLa cells by cellular immunofluorescence assay. Besides, the cellular platinum accumulation of PPS-ALN-Pt conjugates was higher than that of cisplatin in HeLa cells, implying that the polysaccharide-platinum conjugated polymers might have a synergistically therapeutic application in metal anticancer drug delivery.
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http://dx.doi.org/10.1016/j.colsurfb.2021.111628DOI Listing
May 2021

The scale and structure of government financial investment in traditional medicine based on optimal efficiency: evidence from public traditional Chinese medicine hospitals (PTHs) of Henan province, China.

BMC Health Serv Res 2021 Feb 26;21(1):182. Epub 2021 Feb 26.

College of Public Health, Zhengzhou University, 100 Science Avenue Gaoxin District, Zhengzhou, People's Republic of China.

Background: Traditional medicine has been widely used to address relatively common illnesses. In this regard, Chinese government has been continually topping up its investments on public Traditional Chinese Medicine hospitals (PTHs) in recent years. This study aimed to assess the optimal scales and structure of the investments in Henan province by analyzing the contribution of Government Financial Investment (GFI) to the efficiency and revenue growth of PTHs as well as recommending proper investment strategies for implementation to policy-makers.

Methods: This study was a panel data study, conducted in Henan Province, China. By collecting 143 PTHs' operational data from the year 2005 to 2017, Barro Economic Growth (BEG) model, Stochastic Frontier Analysis (SFA) and Vector Autoregressive (VAR) model were used to assess the efficiency and PTHs revenue.

Results: The study observed the positive contribution of GFI to PTHs' revenue growth (average MPG = 2.84), indicating that the GFI had not reached the required optimal level of "Barro Law". In order to maximize the input-output efficiency, the scales of GFI on Grade III, Grade II A, Grade II B PTHs need to be increased by - 5.96, 4.88 and 11.51%, respectively. The third year following the first investment may be a more essential period for conducting an effective GFI evaluation in Henan Province.

Conclusions: GFI on PTHs usually has a long-term impact on PTHs. Governments can adjust its GFI policy so as to maximize the input-output efficiency.
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http://dx.doi.org/10.1186/s12913-021-06185-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908777PMC
February 2021

Association of vitamin D receptor gene polymorphisms with gestational diabetes mellitus-a case control study in Wuhan, China.

BMC Pregnancy Childbirth 2021 Feb 17;21(1):142. Epub 2021 Feb 17.

School of Medicine, Wuhan University of Science and Technology, No.947 Heping Road, Wuhan, China.

Background: Gestational diabetes mellitus (GDM) increased risk of perinatal complications for both the women and the fetuses. The association between the vitamin D receptor (VDR) gene polymorphism and GDM has not been thoroughly investigated in Chinese pregnant women. Therefore, we aimed to determine whether VDR gene single nucleotide polymorphisms (SNPs) rs154410, rs7975232, rs731236, rs2228570 and rs739837 contribute to GDM risk in Wuhan, China. Moreover, we aimed to explore their combined effects on the risk of GDM.

Methods: Pregnant women who had prenatal examinations at 24 to 28 weeks' gestation in our hospital from January 15, 2018 to March 31, 2019 were included in this case-control study. After exclusion, a total of 1684 pregnant women (826 GDM patients and 858 non-diabetic controls) were recruited. The clinical information and blood samples were collected by trained interviewers and nurses. Genotyping of candidate SNPs was conducted on the Sequenom MassARRAY platform. Statistical analyses including t-test, ANOVA, chi-square test and logistic regression were performed to the data with SPSS Software to evaluate differences in genotype distribution and associations with GDM risk. Multifactor dimensionality reduction method was used to explore the gene-gene interactions on the risk of GDM.

Results: Differences in age, pre-pregnancy BMI, family history of diabetes and previous history of GDM between the case and control groups were statistically significant (P < 0.05), whereas no significant differences were found in height, gravidity, parity, and age of menarche (P > 0.05). There were no significant differences at genotype distributions of the examined VDR gene SNPs (P > 0.05). After adjusting by age, pre-pregnancy BMI, family history of diabetes, the results of logistic regression analysis showed no associations of the five SNPs with GDM in all the four genotype models(P > 0.05). Furthermore, there were no gene-gene interactions on the GDM risk among the five examined VDR gene SNPs.

Conclusions: The VDR gene SNPs rs154410, rs7975232, rs731236, rs2228570 and rs739837 showed neither significant associations nor gene-gene interactions with GDM in Wuhan, China.
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http://dx.doi.org/10.1186/s12884-021-03621-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887796PMC
February 2021

The effect of digital health technologies on managing symptoms across pediatric cancer continuum: A systematic review.

Int J Nurs Sci 2021 Jan 27;8(1):22-29. Epub 2020 Oct 27.

Guangzhou Women and Children's Medical Center, Guangzhou, Guangdong, China.

Objective: Pediatric cancer patients endure multiple symptoms during treatment and also in survivorship. Digital health technologies provide an innovative way to support their symptom management. This review aimed to examine the effect of digital health technologies on managing symptoms among across pediatric cancer continuum.

Methods: A systematic literature search of six English and three Chinese electronic databases was combined with hand searching, to identify eligible research studies from database establishment to November 30, 2019. Two reviewers carried out data selection, data extraction, and quality appraisal independently. A narrative approach was taken to summarize data.

Results: Four randomized control trials, two quasi-experiments, and five one group pre-posttest designed studies, were included in the review with a total of 425 participants. The methodological quality of the studies was generally fair. Seven symptoms (anxiety, depression, pain, anger, fatigue, fear, distress) and seven digital health technologies (visual reality, website, humanoid robot, app, wearable devices, short messages and videoconference) were reported in the included studies.

Conclusions: Current evidence supports the effect of digital health technologies is generally mixed and inconclusive. There is a trend of positive effects found in the interventions that feature digital health technologies' interactive function. This review highlights the need for further investigation with rigorous research designs and the consideration of influencing factors from the symptoms, participants, and context levels to inform a better digital health implementation.
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http://dx.doi.org/10.1016/j.ijnss.2020.10.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859551PMC
January 2021

HOXD13 suppresses prostate cancer metastasis and BMP4-induced epithelial-mesenchymal transition by inhibiting SMAD1.

Int J Cancer 2021 Jun 6;148(12):3060-3070. Epub 2021 Mar 6.

State Key Laboratory of Oncogenes and Related Genes, Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

The HOX genes are a group of highly conserved Homeobox-containing genes that control the body plan organization during development. However, their contributions to tumorigenesis and tumor progression remain uncertain and controversial. Here we provided evidence of tumor-suppressive activity of HOXD13 in prostate cancer. HOXD13 depletion contributes to more aggressiveness of prostate cancer cells in vitro and in vivo. These effects were corroborated in a metastatic mice model, where we observed more bone metastatic lesions formed by prostate cancer cells with HOXD13 ablation. Mechanistically, HOXD13 prevents BMP4-induced epithelial-mesenchymal transition (EMT) by inhibiting mothers against decapentaplegic homolog 1 (SMAD1) transcription. Both bioinformation and our tissue microarray cohort data show that HOXD13 expression inversely correlated in advanced prostate cancer patient specimens. Our findings establish HOXD13 as a negative regulator of prostate cancer progression and metastasis by preventing BMP4/SMAD1 signaling, and potentially suggest new strategies for targeting metastatic prostate cancer.
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http://dx.doi.org/10.1002/ijc.33494DOI Listing
June 2021

Enhanced immune memory through a constant photothermal-metabolism regulation for cancer prevention and treatment.

Biomaterials 2021 Mar 19;270:120678. Epub 2021 Jan 19.

College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang, 310058, PR China. Electronic address:

Tumor vaccine inducing effective and perdurable antitumor immunity has a great potential for cancer prevention and therapy. The key indicator for a successful tumor vaccine is boosting the immune system to produce more memory T cells. Although many tumor vaccines have been designed, few of them involve in actively regulating immune memory CD8+T cells. Here a tumor vaccine vector (TA-Met@MS) by encapsulating tumor antigen (TA), metformin (Met) and Hollow gold nanospheres (HAuNS) into poly (lactic-co-glycolic acid) (PLGA) microspheres was presented. TA via the treatment of photothermal therapy (PTT) showed high immunogenicity and immune-adjuvant effectiveness. And NIR light-mediated photothermal effect can lead to a pulsed-release behavior of TA and Met from the microspheres. The released TA can regulate primary T cell expansion and contraction, and stimulate the production of effector T cells at the early immunization stage. The metabolic behavior of the cells is then intervened from glycolysis into fatty acids oxidation (FAO) through the activation of AMPK mediated by Met, which can enhance T cell survival and facilitate the differentiation of memory CD8+T cells. This study may present a valuable insight to design tumor vaccine for enhanced cancer prevention and therapy.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120678DOI Listing
March 2021

Identification of a Nine Immune-Related lncRNA Signature as a Novel Diagnostic Biomarker for Hepatocellular Carcinoma.

Biomed Res Int 2021 5;2021:9798231. Epub 2021 Jan 5.

Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China.

Hepatocellular carcinoma (HCC) ranks fifth among common cancers and is the second most common cause of cancer-related mortality worldwide. This study is aimed at identifying an immune-related long noncoding RNA (lncRNA) signature as a potential biomarker with prognostic value to improve early diagnosis and provide potential therapeutic targets for HCC patients. The subjects of this study were HCC samples with complete transcriptome data and clinical information downloaded from The Cancer Genome Atlas (TCGA) database. We then extracted the immune-related mRNA and lncRNA expression profiles. Based on the expression profiles of immune-related lncRNAs, we identified a nine-lncRNA signature that was related to the progression of HCC. The risk score was calculated based on the expression level of the nine lncRNAs of each sample, which divided patients into high-risk and low-risk groups. We found that the increased risk score was associated with a poor prognosis of HCC patients. To assess the accuracy of the survival model, we calculated a receiver operating characteristic (ROC) for validation. The curve showed that the area under the curve (AUC) for the risk score was 0.792. Besides, both principal component analysis (PCA) and gene set enrichment analysis (GSEA) were further used for functional annotation. We found that the distribution patterns were different between the low-risk and high-risk groups in PCA, and the underlying mechanism by which the nine lncRNAs promoted the progression of HCC involved an abnormal immune status. Finally, we analyzed the infiltration of twenty-nine kinds of immune cells and the activation of immune function in HCC using the ssGSEA algorithm. The results showed that aDCs, iDCs, macrophages, Tfh, Th1, Treg, and NK cells were correlated with the progress of HCC patients. And the immune functions including APC costimulation, CCR, check point, HLA, MHC class I, and Type II IFN responses were also significantly different between the high-risk and low-risk groups. In conclusion, our study identified a nine-lncRNA signature with potential prognostic value for patients with HCC, which could be used as a new biomarker for the diagnosis and immunotherapy of HCC.
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http://dx.doi.org/10.1155/2021/9798231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808810PMC
January 2021

An Anticipatory Circuit Modification That Modifies Subsequent Task Switching.

J Neurosci 2021 Mar 26;41(10):2152-2163. Epub 2021 Jan 26.

Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029

Modulators are generally expected to establish a network configuration that is appropriate for the current circumstances. We characterize a situation where the opposite is apparently observed. A network effect of a peptide modulator is counterproductive in that it tends to impede rather than promote the creation of the configuration that is appropriate when the modulator is released. This raises a question: why does release occur? We present data that strongly suggest that it impacts task switching. Our experiments were conducted in an feeding network that generates egestive and ingestive motor programs. Initial experiments focused on egestive activity and the neuron B8. As activity becomes egestive, there is an increase in synaptic drive to B8 and its firing frequency increases (Wang et al., 2019). We show that, as this occurs, there is also a persistent current that develops in B8 that is outward rather than inward. Dynamic clamp introduction of this current decreases excitability. When there is an egestive-ingestive task switch in , negative biasing is observed (i.e., a bout of egestive activity has a negative impact on a subsequent attempt to initiate an ingestive response) (Proekt et al., 2004). Using an analog of negative biasing, we demonstrate that the outward current that develops during egestive priming plays an important role in establishing this phenomenon. Our data suggest that, although the outward current induced as activity becomes egestive is counterproductive at the time, it plays an anticipatory role in that it subsequently impacts task switching. In this study, we identify a peptide-induced circuit modification (induction of an outward current) that does not immediately promote the establishment of a behaviorally appropriate network configuration. We ask why this might occur, and present data that strongly suggest that it plays an important role during task switching. Specifically, our data suggest that the outward current we characterize plays a role in the negative biasing that is seen in the mollusc when there is a transition from egestive to ingestive activity. It is possible that the mechanism that we describe operates in other species. A negative effect of egestion on subsequent ingestion is observed throughout the animal kingdom.
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http://dx.doi.org/10.1523/JNEUROSCI.2427-20.2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018775PMC
March 2021

Differential expression of αVβ3 and αVβ6 integrins in prostate cancer progression.

PLoS One 2021 22;16(1):e0244985. Epub 2021 Jan 22.

Prostate Cancer Discovery and Development Program, Thomas Jefferson University, Philadelphia, PA, United States of America.

Neuroendocrine prostate cancer (NEPrCa) arises de novo or after accumulation of genomic alterations in pre-existing adenocarcinoma tumors in response to androgen deprivation therapies. We have provided evidence that small extracellular vesicles released by PrCa cells and containing the αVβ3 integrin promote neuroendocrine differentiation of PrCa in vivo and in vitro. Here, we examined αVβ3 integrin expression in three murine models carrying a deletion of PTEN (SKO), PTEN and RB1 (DKO), or PTEN, RB1 and TRP53 (TKO) genes in the prostatic epithelium; of these three models, the DKO and TKO tumors develop NEPrCa with a gene signature comparable to those of human NEPrCa. Immunostaining analysis of SKO, DKO and TKO tumors shows that αVβ3 integrin expression is increased in DKO and TKO primary tumors and metastatic lesions, but absent in SKO primary tumors. On the other hand, SKO tumors show higher levels of a different αV integrin, αVβ6, as compared to DKO and TKO tumors. These results are confirmed by RNA-sequencing analysis. Moreover, TRAMP mice, which carry NEPrCa and adenocarcinoma of the prostate, also have increased levels of αVβ3 in their NEPrCa primary tumors. In contrast, the αVβ6 integrin is only detectable in the adenocarcinoma areas. Finally, analysis of 42 LuCaP patient-derived xenografts and primary adenocarcinoma samples shows a positive correlation between αVβ3, but not αVβ6, and the neuronal marker synaptophysin; it also demonstrates that αVβ3 is absent in prostatic adenocarcinomas. In summary, we demonstrate that αVβ3 integrin is upregulated in NEPrCa primary and metastatic lesions; in contrast, the αVβ6 integrin is confined to adenocarcinoma of the prostate. Our findings suggest that the αVβ3 integrin, but not αVβ6, may promote a shift in lineage plasticity towards a NE phenotype and might serve as an informative biomarker for the early detection of NE differentiation in prostate cancer.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244985PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822502PMC
January 2021

miR-21 Induces Chemoresistance in Ovarian Cancer Cells via Mediating the Expression and Interaction of CD44v6 and P-gp.

Onco Targets Ther 2021 12;14:325-336. Epub 2021 Jan 12.

Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, People's Republic of China.

Background: Ovarian cancer (OC), a representative female reproductive system tumor, is one of the most malignant tumors in female. The most important reason for its poor prognosis is because of its high rate of chemotherapy resistance.

Results: This study aims to explore the effects of miR-21 on the chemotherapy resistance of OC cells. The functions of miR-21 on proliferation, migration and invasion of OC cells were assessed by transwell, clonal formation and CCK8 assay. Expression levels of miR-21, P-gp and CD44v6 in SKOV3 (cisplatin sensitive) cells and SKOV3/DDP (cisplatin resistant) cells were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting. Si-CD44v6 was transfected into OC cells to detect the influence on P-glycoprotein (P-gp) expression. Immunofluorescence was used to detect the localization of CD44v6 and P-gp in cell. Co-immunoprecipitation was used to detect the relationship between CD44v6 and P-gp. Results showed that miR-21 expression in cisplatin-resistant SKOV3/DDP cells was significantly higher than that in SKOV3 cells, at the same time, cells proliferation, as well as invasion and migration ability were enhanced after the miR-21 mimics transfected into SKOV3 cisplatin-sensitive cells. Furthermore, miR-21 expression level affected the CD44v6 and P-gp expression. Immunofluorescence and co-immunoprecipitation showed that CD44v6 and P-gp protein could interact.

Conclusion: In conclusion, the high miR-21 expression level could increase the proliferation, invasion, and migration ability of OC cells. And the interaction of CD44v6 and P-gp may mediate miR-21 involvement in chemotherapy resistance of OC cells.
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http://dx.doi.org/10.2147/OTT.S286639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811474PMC
January 2021

Accuracy of fluoroscopic examination in the treatment of Bennett's fracture.

BMC Musculoskelet Disord 2021 Jan 4;22(1). Epub 2021 Jan 4.

Department of Hand Surgery, Beijing Ji Shui Tan Hospital and the 4th Medical College of Peking University, Xin jie kou dong jie 31, Xi Cheng Qu, Beijing, 100035, China.

Background: Restoration of joint congruity is an important factor for the prevention of subsequent arthritis in patients with Bennett's fracture. Surgical treatment of Bennett's fracture is thus generally recommended for displaced intra-articular fractures to the proximal aspect of the thumb metacarpal. Fluoroscopic examination is used to evaluate the adequacy of closed reduction after pinning of Bennett's fracture. The purpose of this study was to determine the accuracy of fluoroscopy to determine the reduction of Bennett's fractures.

Methods: A model was created, to mimic a Bennett's fracture utilizing ten fresh-frozen cadaveric hands. An oblique cut was made in the proximal aspect of the thumb metacarpal using an oscillating saw. The small oblique fragment involved 1/4-1/3 of the joint surface was then shifted in position creating a step-off or gap at the fracture site. An anatomical reduction model, gap models (1 mm, 2 mm, 3 mm), and step-off models (1 mm, 2 mm, 3 mm) were created using percutaneous fixation with two 1.0 mm Kirschner wires for each cadaveric hand. Fluoroscopic assessment then took place and was reviewed by 2 attending hand surgeons blinded to the actual position. Their estimated fluoroscopic position was then compared to the actual displacement.

Results: The step-off and gap on fluoroscopic examination showed a significant difference compared to the step-off and gap from direct visualization. The frequency of underestimation for the 3 mm displacement models from the fluoroscopic examination was 60%. The frequency for overestimated was 9% for the models in which displacement was within 2 mm (0, 1, 2 mm).

Conclusions: The assessment of articular gap and step-off using PA (postero-anterior), AP (antero-posterior), and lateral view of fluoroscopic examination is not accurate as compared to the examination by direct visualization. Surgeons need to be aware that PA, AP and lateral view of fluoroscopic examination alone may not be sufficient to judge the final position of a reduced Bennett's fracture. Other methods such as live fluoroscopy in multiple different planes, 3-dimensional fluoroscopy or arthroscopic examination should be considered.
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http://dx.doi.org/10.1186/s12891-020-03867-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783999PMC
January 2021

Discovery of extracellular vesicles derived miR-181a-5p in patient's serum as an indicator for bone-metastatic prostate cancer.

Theranostics 2021 1;11(2):878-892. Epub 2021 Jan 1.

Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.

To identify extracellular vesicle (EV)-delivered microRNAs in the patient's serum as indicators for bone-metastatic prostate cancer. First, the profiling change of serum EV-delivered miRNAs in patients with either benign prostatic hyperplasia (BPH), non-bone metastatic prostate cancer or bone-metastatic prostate cancer was detected by microRNA deep sequencing assay and microRNA-chip array assay, respectively. Second, the candidates were further confirmed using TaqMan microRNA assay in two independent validation cohorts of total 176 patients with either BPH, non-bone metastatic prostate cancer or bone metastatic prostate cancer to seek the most valuable microRNA(s). Through microRNA deep sequencing and microRNA-chip array, we found 4 prospective EV-delivered miRNAs including miR-181a-5p with significantly upregulated expression in bone metastatic groups than in non-bone metastatic prostate cancer groups (p < 0.05). In the validation cohorts, logistic regression analysis was performed to evaluate the diagnostic association of candidates with bone metastasis, which indicated that miR-181a-5p was significantly associated with bone metastatic prostate cancer. Furthermore, accuracy estimate of each candidate for the diagnosis of bone metastatic prostate cancer was quantified using the area under the receiver-operating characteristic curve (AUC), which identified miR-181a-5p as the best biomarker with the AUCs of 85.6% for diagnosis of prostate cancer and 73.8% for diagnosis of bone metastatic prostate cancer. EV-delivered miR-181a-5p from patient's serum is a promising diagnostic biomarker for bone metastatic prostate cancer.
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http://dx.doi.org/10.7150/thno.49186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738844PMC
January 2021

Single-cell analysis supports a luminal-neuroendocrine transdifferentiation in human prostate cancer.

Commun Biol 2020 Dec 16;3(1):778. Epub 2020 Dec 16.

State Key Laboratory of Oncogenes and Related Genes, Renji-Med-X Stem Cell Research Center, Department of Urology, Ren Ji Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200127, China.

Neuroendocrine prostate cancer is one of the most aggressive subtypes of prostate tumor. Although much progress has been made in understanding the development of neuroendocrine prostate cancer, the cellular architecture associated with neuroendocrine differentiation in human prostate cancer remain incompletely understood. Here, we use single-cell RNA sequencing to profile the transcriptomes of 21,292 cells from needle biopsies of 6 castration-resistant prostate cancers. Our analyses reveal that all neuroendocrine tumor cells display a luminal-like epithelial phenotype. In particular, lineage trajectory analysis suggests that focal neuroendocrine differentiation exclusively originate from luminal-like malignant cells rather than basal compartment. Further tissue microarray analysis validates the generality of the luminal phenotype of neuroendocrine cells. Moreover, we uncover neuroendocrine differentiation-associated gene signatures that may help us to further explore other intrinsic molecular mechanisms deriving neuroendocrine prostate cancer. In summary, our single-cell study provides direct evidence into the cellular states underlying neuroendocrine transdifferentiation in human prostate cancer.
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http://dx.doi.org/10.1038/s42003-020-01476-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745034PMC
December 2020

DNA topoisomerases as additional targets for anticancer monofunctional platinum(ii) complexes.

Dalton Trans 2021 Jan 10;50(1):304-310. Epub 2020 Dec 10.

State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, P. R. China.

Topoisomerases are ubiquitous enzymes and important targets for DNA-oriented anticancer drugs. Two mitochondrion-targeted monofunctional platinum(ii) complexes, [Pt(ortho-PPhCHPy)(NH)Cl](NO) (OPT) and [Pt(para-PPhCHPy)(NH)Cl](NO) (PPT; PPh = triphenylphosphonium, Py = pyridine), show significant inhibition towards the activity of DNA topoisomerases in addition to their DNA binding and mitochondrial targeting capabilities. OPT exhibits strong cytotoxicity toward the human renal clear cell carcinoma 786-O and the murine prostate cancer RM-1 cell lines. The complex could bind to the minor groove of DNA, as well as DNA topoisomerases I and IIα, thereby acting as an inhibitor of topoisomerase I/IIα and causing DNA damage. The damage was evidenced by the enhanced expression of γ-H2AX, Chk1/2 phosphorylation, p53 and cell cycle arrest in the G2/M phase. In contrast, the inhibitory effect of PPT on DNA topoisomerases was largely limited to the isolated enzymes. The results demonstrate that the cellular inhibition of the complex towards the DNA topoisomerases positively correlated with its mitochondrial accumulation. Molecular docking provided more detailed structural insights into the interactions of OPT or PPT with DNA and topoisomerase I/IIα. The binding sites of OPT and PPT in topoisomerase-DNA complexes are different from each other. Aside from previously revealed DNA and mitochondrial targets, this study discovered new evidence that DNA topoisomerases may also serve as targets of monofunctional platinum(ii) complexes. For a multispecific platinum complex, strong DNA binding ability does not necessarily lead to potent cytotoxicity as other factors including the cell types, mitochondrial accumulation, and activity of DNA topoisomerases also affect the outcome of DNA damage.
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http://dx.doi.org/10.1039/d0dt02608eDOI Listing
January 2021

[Corrigendum] Molecular mechanism of extracellular matrix disorder in pelvic organ prolapses.

Mol Med Rep 2021 01 25;23(1). Epub 2020 Nov 25.

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.

Subsequently to the publication of the above article, the authors have realized that the bar charts shown for Fig. 3A and B, as they appeared in the paper, were the same as the bar charts shown for Fig. 4B and D. Fig. 3, as it should have appeared, is shown below. All the authors agree to this Corrigendum. Note that the revisions made to this figure do not adversely affect the results reported in the paper, or the conclusions stated therein. The authors regret that the duplication of the histograms in Fig. 4 as Fig. 3 was not noticed prior to the publication of this article, and offer their apologies to the Editor of Molecular Medicine Reports and to the readers of the Journal. [the original article was published in Molecular Medicine Reports 22: 4611-4618, 2020; DOI: 10.3892/mmr.2020.11564].
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http://dx.doi.org/10.3892/mmr.2020.11721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716395PMC
January 2021

Effects of Chinese Herbal Medicine on Acute Exacerbations of COPD: A Randomized, Placebo-Controlled Study.

Int J Chron Obstruct Pulmon Dis 2020 12;15:2901-2912. Epub 2020 Nov 12.

Nanyang City Center Hospital, Nanyang, People's Republic of China.

Purpose: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is an essential occurrence in COPD management and is the leading cause of morbidity and mortality. Chinese herbal medicine is widely used in the treatment of AECOPD, but high quality randomized controlled trials are limited. This study aimed to evaluate the efficacy and safety of Chinese herbal medicine as adjuvant therapy for patients with AECOPD.

Methods: This was a randomized, double-blind, placebo-controlled study of 378 participants from eight centers in China. Participants were randomly assigned to receive 10 g of Chinese herbal medicine (according to the type of Traditional Chinese medicine syndrome: Sanhanhuayin, Qingrehuatan, or Zaoshihuatan granules) or placebo, two times per day, for 14 days, in addition to conventional medicine. Participants were followed up for 84 days after the treatment. The primary end point was the COPD assessment test (CAT) score. Secondary end points included the Modified British Medical Research Council (mMRC) questionnaire and the COPD patient-reported outcome scale (COPD-PRO). We also assessed treatment failure and treatment success rate, length of hospitalization, number of patients with acute exacerbations, number of patients readmitted due to AECOPD, and number of deaths and intubation.

Results: The between-group difference in the change from baseline for CAT on day 14 (end of treatment) was -2.11 (95% confidence interval [CI], -3.198 to -1.050; P<0.001), exceeding the minimal clinically important difference. The mMRC and COPD-PRO scores were lower in the intervention group compared to the control group (between-group difference in the change from baseline, -0.28; 95% CI, -0.48 to -0.08; P=0.007 and -2.51; 95% CI, -4.087 to -0.929; P=0.002, respectively) on day 14. The intervention group had a significantly shorter duration of hospital stay than the control group (mean difference, -1.21days; 95% CI, -2.041 to -0.419; P=0.003), significantly lower of number of exacerbations (risk ratio [RR], 0.60; 95% CI, 0.409 to 0.892; P=0.010), and significantly lower number of readmissions due to AECOPD (RR, 0.41; 95% CI, 0.193 to 0.865; P=0.015). Significant differences in the number of treatment failures or successes, deaths, and intubation were not observed. The difference in safety variables and adverse events between the two groups was not observed.

Conclusion: Chinese herbal medicine appears to be safe and beneficial for AECOPD and can be considered a complementary treatment for patients with AECOPD.
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http://dx.doi.org/10.2147/COPD.S276082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670171PMC
November 2020

History of the COVID-19 pandemic: Origin, explosion, worldwide spreading.

Biochem Biophys Res Commun 2021 01 6;538:14-23. Epub 2020 Nov 6.

Venetian Institute of Molecular Medicine, University of Padova, Italy. Electronic address:

The SARS-CoV-2 virus of the COVID-19 pandemic, that is presently devastating the entire world, had been active well before January of this year, when its pathogenic potential exploded full force in Wuhan. It had caused the onset of small disease outbreaks in China, and probably elsewhere as well, which failed to reach epidemic potential. The distant general origin of its zoonosis can be traced back to the ecosystem changes that have decreased biodiversity, greatly facilitating the contacts between humans and the animal reservoirs that carry pathogens, including SARS-CoV-2. These reservoirs are the bats. The transition between the limited outbreaks that had occurred through 2019 and the epidemic explosion of December-January was made possible by the great amplification of the general negative conditions that had caused the preceding small outbreaks. In the light of what we have now learned, the explosion was predictable, and could have happened wherever the conditions that had allowed it, could be duplicated. What could not have been predicted was the second transition, from epidemic to pandemic. Research has now revealed that the globalization of the infection appears to have been caused by a mutation in the spike protein of the SARS-CoV-2, that has dramatically increased its transmissibility.
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http://dx.doi.org/10.1016/j.bbrc.2020.10.087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834510PMC
January 2021

Molecular mechanism of extracellular matrix disorder in pelvic organ prolapses.

Mol Med Rep 2020 Dec 6;22(6):4611-4618. Epub 2020 Oct 6.

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.

Pelvic organ prolapses (POP) notably reduces the quality of life in elderly populations due to bladder and bowel dysfunction, incontinence, and coital problems. Extracellular matrix (ECM) disorder is a pivotal event in the progression of POP, but to date, its specific underlying mechanism remains unclear. The ligaments of patients with POP and healthy controls were collected to compare the expression of Homeobox11 (HOXA11) and transforming growth factor β (TGF‑β1) via immunohistochemical analysis. HOXA11 and TGF‑β1 were overexpressed or knocked down in fibroblast cells to explore their effects on the expression of collagen and matrix metalloproteinases (MMPs). HOXA11 and TGF‑β1 were greatly reduced in the ligaments of patients with POP. The overexpression and downregulation of HOXA11 and TGF‑β1 can mediate ECM disorder via regulating expression of collagen (Col) and MMPs. In addition, HOXA11 and TGF‑β1 exerted synergistic effect on the expression of Col and MMPs. The present study identified that HOXA11 and TGF‑β1 serve critical roles in mediating ECM disorders, which may be of clinical significance for the diagnosis and treatment of patients with POP.
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http://dx.doi.org/10.3892/mmr.2020.11564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646844PMC
December 2020

Inhibition of Aβ aggregates in Alzheimer's disease by epigallocatechin and epicatechin-3-gallate from green tea.

Bioorg Chem 2020 12 15;105:104382. Epub 2020 Oct 15.

School of Life Sciences, Nanjing University, Nanjing 210023, PR China. Electronic address:

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive accumulation of senile plaques, which are primarily composed of misfolded amyloid β-peptide (Aβ). Aβ aggregates are believed to be a key factor in the pathogenesis of AD, affecting the nervous system in human body. The therapeutic potential of tea-derived polyphenolic compounds, (-)-epigallocatechin (EGC) and (-)-epicatechin-3-gallate (ECG), for AD was investigated by assessing their effects on the Cu/Zn-induced or self-assembled Aβ aggregation using thioflavine T fluorescent spectrometry, inductively coupled plasma mass spectrometry, UV-Vis spectroscopy, transmission electron microscope, silver staining, immunohistochemistry, and immunofluorescence assays. EGC and ECG mildly bind to Cu and Zn, and diminish the Cu- or Zn-induced or self-assembled Aβ aggregates; they also modulate the Cu/Zn-Aβ induced neurotoxicity on mouse neuroblastoma Neuro-2a cells by reducing the production of ROS. Metal chelating, hydrogen bonding or Van Der Waals force may drive the interaction between the polyphenolic compounds and Aβ. The results demonstrate that green tea catechins EGC and ECG are able to alleviate the toxicity of Aβ oligomers and fibrils. Particularly, ECG can cross the blood-brain barrier to reduce the Aβ plaques in the brain of APP/PS1 mice, thereby protecting neurons from injuries. The results manifest the potential of green tea for preventing or ameliorating the symptoms of AD.
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http://dx.doi.org/10.1016/j.bioorg.2020.104382DOI Listing
December 2020

The Application of Three-Dimensional Technology Combined With Image Navigation in Nasal Skull Base Surgery.

J Craniofac Surg 2020 Nov/Dec;31(8):2304-2309

Department of Otorhinolaryngology Head and Neck Surgery.

Three-dimensional (3D) technology including 3D reconstruction and 3D printing technology, has been widely used in clinical treatment, especially in surgical planning, and image navigation technology, which can make surgical procedures more accurate, now is also increasingly favored by surgeons. But the combination of those 2 technologies was rarely reported. Thus, this study will preliminarily investigate the feasibility and the effect of the combination of 2 technologies in endonasal skull base surgery. Eight patients were involved in this study (from October 2016 to July 2017 at The Affiliated Hospital of Qingdao University), 5 cases of nasal skull base tumors and 3 cases of foreign body perforation. All operations were done under the assistance of 3D technology and image guidance system. Surgical discussion with patient, preoperative planning and clinical teaching were investigated between 2D images and 3D models by voting. For all cases, 3D reconstruction model and 3D printed model were deemed to be more helpful than CT/MRI images in surgical discussion with the patient; surgical simulation on 3D model in preoperative planning was largely deemed to be helpful and very helpful; and in clinical teaching, 3D models combined with image guidance system were deemed to be more helpful in understanding the disease than using 2D images. Besides, all patients recovered well after surgery, no recurrence and complications were found in the follow-up. The combination of 3D technology and electromagnetic image guidance system could improve surgical efficiency and the quality of clinical teaching.
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http://dx.doi.org/10.1097/SCS.0000000000006913DOI Listing
April 2021

CTLA4 has a profound impact on the landscape of tumor-infiltrating lymphocytes with a high prognosis value in clear cell renal cell carcinoma (ccRCC).

Cancer Cell Int 2020 27;20:519. Epub 2020 Oct 27.

Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, 430060 Hubei Province People's Republic of China.

Background: Cytotoxic T-lymphocyte associated protein 4 (CTLA4) inhibitors have been shown to significantly prolong the overall survival (OS) in a wide range of cancers. However, its application in clear cell renal cell carcinoma (ccRCC) is limited due to the therapy response, and the prognostic value of CTLA4 in ccRCC has not been investigated in detail.

Methods: By using immunohistochemistry, Kaplan-Meier (K-M) analysis, uni- and multi-variate Cox analysis, we comprehensively and systematically studied the prognostic value of CTLA4 in ccRCC. Then, we applied Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG) and CIBERSORT, ESTIMATE algorithm, ssGSEA and somatic mutation analyses to reveal the impact of CTLA4 on the landscape of tumor-infiltrating lymphocytes (TILs) infiltration and genetic mutation. Besides, given current concerns caused by combined immunotherapy, we also investigated the relationship between CTLA4 and other immune checkpoints.

Results: In vitro experiment and data mining showed that, CTLA4 was up-regulated in ccRCC tissues and closely related to the disease progression as well as a poor prognosis. Deeper researches demonstrated that CTLA4 regulates T cell activation and was significantly linked to TIL-abundant tumor microenvironment (TME), but was accompanied by an immunosuppressed phenotype. Mutation analysis showed that CTLA4 was associated with more frequent BRCA-associated protein 1 (BAP1) mutation. Moreover, we found that CTLA4 was markedly correlated with multiple immune checkpoints, which suggested that ccRCC patients with high expressed CTLA4 may benefit more from immune checkpoint blockades (ICBs) combined therapy.

Conclusion: CTLA4 has a profound impact on the landscape of TILs and genetic mutation, and can be used as the biomarker with high prognosis value in ccRCC.
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http://dx.doi.org/10.1186/s12935-020-01603-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590466PMC
October 2020

Effect of arsenic trioxide on cervical cancer and its mechanisms.

Exp Ther Med 2020 Dec 9;20(6):169. Epub 2020 Oct 9.

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi 710061, P.R. China.

Cervical cancer is one of the most common types of gynecological tumor, and thus identifying complementary or substitute treatment methods to treat cervical cancer is important. The present study aimed to evaluate the effect of arsenic trioxide (ATO), a traditional Chinese medicine, on cervical cancer cells and its underlying mechanism. MTT, colony formation and Transwell assays were performed to investigate the effects of different concentrations of ATO on cell proliferation and invasion, respectively. Western blotting and reverse transcription-quantitative PCR were applied to measure hypoxia-inducible factor-1α expression (HIF-1α) expression following ATO treatment. Finally, the effects of HIF-1α knockdown on cervical cancer cell proliferation, apoptosis and invasion were evaluated. The results demonstrated that ATO could inhibit cell proliferation and invasion. Moreover, ATO could induce reactive oxygen species production in a time- and dose-dependent manner. ATO could also promote the apoptosis of cervical cancer cells via HIF-1α. Therefore, the present study may provide a theoretical basis for identifying effective molecular targets for the prevention and treatment of cervical cancer.
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http://dx.doi.org/10.3892/etm.2020.9299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7579781PMC
December 2020

Biodiversity loss and COVID-19 pandemic: The role of bats in the origin and the spreading of the disease.

Biochem Biophys Res Commun 2021 01 16;538:2-13. Epub 2020 Oct 16.

Venetian Institute of Molecular Medicine, University of Padova, Italy. Electronic address:

The loss of biodiversity in the ecosystems has created the general conditions that have favored and, in fact, made possible, the insurgence of the COVID-19 pandemic. A lot of factors have contributed to it: deforestation, changes in forest habitats, poorly regulated agricultural surfaces, mismanaged urban growth. They have altered the composition of wildlife communities, greatly increased the contacts of humans with wildlife, and altered niches that harbor pathogens, increasing their chances to come in contact with humans. Among the wildlife, bats have adapted easily to anthropized environments such as houses, barns, cultivated fields, orchards, where they found the suitable ecosystem to prosper. Bats are major hosts for αCoV and βCoV: evolution has shaped their peculiar physiology and their immune system in a way that makes them resistant to viral pathogens that would instead successfully attack other species, including humans. In time, the coronaviruses that bats host as reservoirs have undergone recombination and other modifications that have increased their ability for inter-species transmission: one modification of particular importance has been the development of the ability to use ACE2 as a receptor in host cells. This particular development in CoVs has been responsible for the serious outbreaks in the last two decades, and for the present COVID-19 pandemic.
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http://dx.doi.org/10.1016/j.bbrc.2020.10.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566801PMC
January 2021