Publications by authors named "Liang Zhou"

1,069 Publications

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The Inhibitory Effects of Ficin on Biofilm Formation.

Biomed Res Int 2021 23;2021:6692328. Epub 2021 Mar 23.

School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou 325027, China.

To investigate the effects of ficin on biofilm formation of conditionally cariogenic (). Biomass and metabolic activity of biofilm were assessed using crystal violet assay, colony-forming unit (CFU) counting, and MTT assay. Extracellular polysaccharide (EPS) synthesis was displayed by SEM imaging, bacteria/EPS staining, and anthrone method while acid production was revealed by lactic acid assay. Growth curve and live/dead bacterial staining were conducted to monitor bacterial growth state in both planktonic and biofilm form. Total protein and extracellular proteins of biofilm were analyzed by protein/bacterial staining and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), severally. qRT-PCR was conducted to detect acid production, acid tolerance, and biofilm formation associated genes. Crystal violet assay, CFU counting, and MTT assay showed that the suppression effect of ficin on biofilm formation was concentration dependent. 4 mg/mL ficin had significant inhibitory effect on biofilm formation including biomass, metabolic activity, EPS synthesis, and lactic acid production ( < 0.05). The growth curves from 0 mg/mL to 4 mg/mL ficin were aligned with each other. There was no significant difference among different ficin groups in terms of live/dead bacterial staining result ( > 0.05). Protein/bacterial staining outcome indicated that ficin inhibit both total protein and biofilm formation during the biofilm development. There were more relatively small molecular weight protein bands in extracellular proteins of 4 mg/mL ficin group when compared with the control. Generally, ficin could inhibit biofilm formation and reduce cariogenic virulence of effectively in vitro; thus, it could be a potential anticaries agent.
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http://dx.doi.org/10.1155/2021/6692328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009705PMC
March 2021

Long Non-Coding RNA LOC648987 Promotes Proliferation and Metastasis of Renal Cell Carcinoma by Regulating Epithelial-Mesenchymal Transition.

Technol Cancer Res Treat 2021 Jan-Dec;20:1533033821997834

Department of General Practice, Ningbo Beilun People's Hospital, Ningbo, Zhejiang, China.

Renal cell carcinoma (RCC) is a type of urinary tumor with a high incidence and is often associated with tumor metastasis. Long non-coding RNA (lncRNA) regulates tumorigenesis, progression, and metastasis. However, the role and the predictive value of lncRNA in RCC progression and metastasis have not been elucidated. The purpose of this study was to evaluate the effect of a newly discovered lncRNA LOC648987 on RCC proliferation and metastasis. LOC648987 was identified by RT-PCR for high expression in human RCC tissues as well as in metastatic RCC tissues. In the cell experiments, we infected the RCC cell lines ACHN and 786-O cells with LOC648987-shRNA and its negative control (shNC). The results showed that the knockdown of LOC648987 inhibited the proliferation of ACHN and 786-O cells and colony formation. The cell cycle and the apoptosis progression of ACHN and 786-O cells were assessed using flow cytometry. The knockdown of LOC648987 significantly inhibited the progression of ACHN and 786-O cells from G0/G1 to S phase and promoted cell apoptosis. The metastasis promoting effects of LOC648987 on ACHN and 786-O cells were verified by transwell migration assays, which depended on vimentin and MMP-9 to regulate the epithelial-mesenchymal transition. Finally, the promotion of LOC648987 on RCC tumorigenesis was evaluated in BALb/c nude mice. These data confirmed that lncRNA LOC648987 promoted RCC cell proliferation and tumor metastasis and regulated the expression of EMT-related proteins in RCC cells.
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http://dx.doi.org/10.1177/1533033821997834DOI Listing
April 2021

LncRNA RUSC1-AS1 contributes to the progression of hepatocellular carcinoma cells by modulating miR-340-5p/CREB1 axis.

Am J Transl Res 2021 15;13(3):1022-1036. Epub 2021 Mar 15.

Department of General Surgery, BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University Nanjing, Jiangsu, China.

Background: Recent studies have proven that there is a relationship between long non-coding RNAs (lncRNAs) and malignant tumor hepatocellular carcinoma (HCC). However, the function of RUSC1-AS1 and its relative regulators in HCC remains unknown.

Methods: studies, CCK-8 assays, colony formation assays, transwell assays, and wound healing tests were carried out to evaluate the proliferation, migration, and invasion of HCC cells. The correlation between RUSC1-AS1 expression with tumor size or weight was studied in nude mice. Bioinformatics analysis, dual luciferase, quantitative Real-Time PCR (qRT-PCR), and Western blot analysis aimed to discover the relevance between miR-340-5p and RUSC1-AS1 or cAMP responsive element binding protein 1 (CREB1).

Results: When compared with normal groups, RUSC1-AS1 expression in HCC tissues and HCC cell lines was higher. We also found that knockdown of RUSC1-AS1 inhibited HCC cell progression, including proliferation, migration, and invasion, and suppressed tumorigenesis . Further studies demonstrated that the expression of RUSC1-AS1 negatively correlated with miR-340-5p expression in HCC cells. In addition, miR-340-5p was identified as a direct target of RUSC1-AS1 and tightly associated with the prevention of tumor progression. Moreover, miR-340-5p bound directly to CREB1. CREB1 overexpression reversed the impact of miR-340-5p on HCC cells. Together, lncRNA RUSC1-AS1 plays a regulatory role in the PI3K/AKT signaling pathway in HCC cells.

Conclusion: We demonstrated that lncRNA RUSC1-AS1 influenced HCC cell progression by modulating its downstream target miR-340-5p/CREB1 axis via the PI3K/AKT signaling pathway, which may be a potential prognostic and therapeutic target for treating HCC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014390PMC
March 2021

Design, synthesis, biological evaluation and molecular dynamics of LAR inhibitors.

Comput Biol Chem 2021 Mar 30;92:107481. Epub 2021 Mar 30.

Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin, China. Electronic address:

In this study, firstly, the pharmacophore model was established based on LAR inhibitors. ZINC database and drug-like database were screened by Hypo-1-LAR model, and the embryonic compound ZINC71414996 was obtained. Based on this compound, we designed 9 compounds. Secondly, the synthetic route of the compound was determined by consulting Reaxys and Scifinder databases, and 9 compounds (1a-1i) were synthesized by nucleophilic substitution, Suzuki reaction and so on. Meanwhile, their structures were confirmed by H NMR and C NMR. Thirdly, the Enzymatic assays was carried out, the biological evaluation of compounds 1a-1i led to the identification of a novel PTP-LAR inhibitor 1c, which displayed an IC value of 4.8 μM. At last, molecular dynamics simulation showed that compounds could interact strongly with the key amino acids LYS1350, LYS1352, ARG1354, TYR1355, LYS1433, ASP1435, TRP1488, ASP1490, VAL1493, SER1523, ARG1528, ARG1561, GLN1570, LYS1681, thereby inhibiting the protein activity. This study constructed the pharmacophore model of LAR protein, designed small-molecule inhibitors, conducted compound synthesis and enzyme activity screening, so as to provide a basis for searching for drug-capable lead compounds.
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http://dx.doi.org/10.1016/j.compbiolchem.2021.107481DOI Listing
March 2021

Effect of Exercise on Fatigue in Patients with Lung Cancer: A Systematic Review and Meta-Analysis of Randomized Trials.

J Palliat Med 2021 Apr 9. Epub 2021 Apr 9.

Second Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China.

Fatigue is a frequent debilitating symptom among patients with lung cancer. The effect of exercise on fatigue remains to be quantified. This review aimed to examine the effect of exercise on fatigue by synthesizing findings from randomized controlled trials (RCTs). This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search was conducted in five electronic databases from inception to March 2020. Only RCT was included. The primary outcome was fatigue and the secondary outcomes included depression, anxiety, quality of life, and functional capacity. Pooled weighted or standardized mean difference (WMD or SMD) with 95% confidence interval (CI) was calculated. Eight RCTs were included. The exercise intervention was delivered in the supervised environment ( = 6) or free-living settings ( = 2). Exercise reduced the level of fatigue (SMD = -0.33; 95% CI = -0.54 to -0.13). Exercise also decreased depressive symptom (WMD = -1.57; 95% CI = -2.69 to -0.44) and anxiety (WMD = -1.39; 95% CI = -2.60 to -0.18). Exercise showed a moderate effect on the quality of life, with an SMD of 0.33 (95% CI = 0.08 to 0.58). Exercise intervention increased functional capacity as measured by the six-minute walk test by 20 meters (95% CI = 14.2 to 55.0), but the effect was not significant ( = 0.247). Exercise demonstrated a moderate effect on fatigue in patients with lung cancer. Exercise also improved depressive symptoms, anxiety, and quality of life; however, its impact on functional capacity was not significant. More clinical trials are warranted to explore the mechanisms underlying the impact of exercise on fatigue. Strategies improving adherence to exercise prescription should be developed to help these patients overcome potential challenges.
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http://dx.doi.org/10.1089/jpm.2020.0504DOI Listing
April 2021

Predictive Modeling of Lignin Content for the Screening of Suitable Poplar Genotypes Based on Fourier Transform-Raman Spectrometry.

ACS Omega 2021 Mar 18;6(12):8578-8587. Epub 2021 Mar 18.

School of Forestry and Landscape Architecture, Anhui Agriculture University, Hefei 230036, Anhui, China.

The quick and non-invasive evaluation of lignin from biomass has been the focus of much attention. Several types of spectroscopies, for example, near-infrared (NIR) and Fourier transform-Raman (FT-Raman), have been successfully applied to build quantitative predictive lignin models based on chemometrics. However, due to the effect of sample moisture content and ambient humidity on its signals, NIR spectroscopy requires sophisticated pre-testing preparation. In addition, the current FT-Raman predictive models require large variations in the independent value inputs as restrictions in the corresponding mathematical algorithms prevent the effective biomass screening of suitable genotypes for lignin contents within a narrow range. In order to overcome the limitations associated with the current methods, in this paper, we employed Raman spectra excited using a 1064 nm laser, thus avoiding the impact of water and auto-fluorescence on NIR signals. The optimal baseline correction method, data type, mathematical algorithm, and internal reference were selected in order to build quantitative lignin models based on the data with limited variation. The resulting two predictive models, constructed through lasso and ridge regressions, respectively, proved to be effective in assessing the lignin content of poplar in large-scale breeding and genetic engineering programs.
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http://dx.doi.org/10.1021/acsomega.1c00400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015071PMC
March 2021

Improved Efficiency Roll-Off and Operational Lifetime of Organic Light-Emitting Diodes with a Tetradentate Platinum(II) Complex by Using an n-Doped Electron-Transporting Layer.

Molecules 2021 Mar 24;26(7). Epub 2021 Mar 24.

State Key Laboratory of Synthetic Chemistry, HKU-CAS Joint Laboratory on New Materials, Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, China.

The efficiency roll-off and operational lifetime of organic light-emitting diodes (OLEDs) with a tetradentate Pt(II) emitter is improved by engaging an n-doped electron-transporting layer (ETL). Compared to those devices with non-doped ETL, the driving voltage is lowered, the charged carrier is balanced, and the exciton density in the emissive layer (EML) is decreased in the device with n-doped ETL with 8-hydroxyquinolinolatolithium (Liq). High luminance of almost 70,000 cd m and high current efficiency of 40.5 cd A at high luminance of 10,000 cd m is achieved in the device with 50 wt%-Liq-doped ETL. More importantly, the extended operational lifetime of 1945 h is recorded at the initial luminance of 1000 cd m in the 50 wt%-Liq-doped device, which is longer than that of the device with non-doped ETL by almost 10 times. This result manifests the potential application of tetradentate Pt(II) complexes in the OLED industry.
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http://dx.doi.org/10.3390/molecules26071835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037627PMC
March 2021

Identifying multimorbidity patterns of non-communicable diseases in paediatric inpatients: a cross-sectional study in Shanghai, China.

BMJ Open 2021 Apr 1;11(4):e042679. Epub 2021 Apr 1.

Department of General Practice, Tongji University Affiliated Yangpu Hospital, Shanghai, China

Objectives: To enhance the understanding of non-communicable disease (NCD) multimorbidity in children who are inpatients by delineating the characteristics of and identifying patterns among paediatric inpatients with multimorbidity in China.

Design: Cross-sectional study.

Setting: Paediatric wards (n=17) in Pudong New Area, Shanghai, China.

Participants: A total of 193 432 paediatric inpatients in the electronic health record systems of 17 hospitals from 2011 to 2016 participated in the study, and 91 004 children with NCDs were extracted and classified based on International Classification of Diseases, 10th version codes.

Main Outcome Measures: Number of the NCDs and multimorbidity patterns of the paediatric inpatients.

Results: In total, 47.05% (95% CI 46.83 to 47.27) of the paediatric inpatients had one or more chronic diseases, and 16.30% (95% CI 16.14 to 16.46) had multimorbidity. Congenital anomalies accounted for 19.43% (95% CI 19.25 to 19.61) of the principal diagnoses among the paediatric inpatients. Five common multimorbidity patterns were identified: a neurological-respiratory cluster, a neurological-respiratory-ear cluster, a cardiovascular-circulatory cluster, a genitourinary cluster (boy group) and a musculoskeletal-connective cluster (10-18 years age group).

Conclusions: Multimorbidity in paediatric inpatients suggests that decisions about reasonable allocation of paediatric inpatient resources should be fully considered. Multimorbidity patterns in paediatric inpatients revealed that prevention, including innovative treatments targeting children, should be further studied.
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http://dx.doi.org/10.1136/bmjopen-2020-042679DOI Listing
April 2021

[Pathologic tumor volume predicting survival outcomes of patients with local advanced glottic carcinoma].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2021 Apr;35(4):316-320

Department of Otolaryngology Head and Neck Surgery,Eye & ENT Hospital of Fudan University,Shanghai,200031,China.

The aim of this study was to evaluate the predicting role of tumor volume as evaluated by postoperative pathologic examination on overall survival(OS) and disease free survival(DFS) in patients with local advanced glottic carcinoma. In this study, the records of 406 consecutive patients with local advanced glottic carcinoma(T3-T4 stages) who underwent surgery ± chemoradiotherapy from January 2005 to December 2010 were retrospectively reviewed and followed up. The demographic characteristics, disease staging, and pathologic tumor volume were analyzed. The optimal cutoff values of tumor volume for OS and DFS were obtained by using receiver operating characteristic(ROC) curves. The association of tumor volume with T stages were assessed by using Logistic regression model, and the relationship between tumor volume and OS and DFS rates were evaluated by using Cox regression models. The 5-and 10-year OS rates were 62.9% and 55.4%, respectively. The 5-and 10-year DFS rates were 55.5% and 50.8%, respectively. The mean tumor volume was(5.1±6.7) cm³, T4 stage patients had higher tumor volume than those of patients with T3 stage(<0.001). The factor of tumor volume was correlated with T stages by using Logistic regression analyses(=13.81, 95%: 6.03-31.59, <0.001). The optimal cutoff values of tumor volume that were both at 3 cm³ for OS and DFS rates were obtained by using ROC curve plots. The OS and DFS rates of glottic carcinoma patients with tumor volume ≤ 3 cm³ were better when compared with those of patients with tumor volume>3 cm³(<0.001). Upon multivariate analyses, tumor volume was strongly correlated with poorer OS and DFS rates and remained independent prognostic factors for both the OS and DFS of patients with glottic carcinoma(OS: =1.59, 95%: 1.09-2.32, =0.017; DFS: =1.54, 95%: 1.08-2.20, =0.016). This study demonstrates that tumor volume is correlated with T stages, and this factor is an independent predictive factor of survival outcomes in patients with local advanced glottic carcinoma.
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http://dx.doi.org/10.13201/j.issn.2096-7993.2021.04.007DOI Listing
April 2021

Distribution and Transformation of Mercury in Subtropical Wild-Caught Seafood from the Southern Taiwan Strait.

Biol Trace Elem Res 2021 Apr 1. Epub 2021 Apr 1.

Key Laboratory of Estuarine Ecological Security and Environmental Health, Education Department of Fujian, Tan Kah Kee College, Xiamen University, Zhangzhou, 363105, China.

Wild-caught seafood contains significant amounts of mercury. Investigating the mercury accumulation levels in wild-caught seafood and analyzing its migration and transformation are of great value for assessing the health risks of mercury intake and for the tracking of mercury sources. We determined the concentrations and stable mercury isotopic compositions (δHg, ΔHg, ΔHg, and ΔHg) of 104 muscle samples collected from 38 species of seafood typically harvested from the Taiwan Shallow Fishing Ground (TSFG), Southern Taiwan Strait. Overall, the concentrations of total mercury (THg) and methylmercury (MeHg) ranged from 11 to 479 ng/g (dry weight, dw) and 10 to 363 ng/g (dw), respectively, and were below the threshold value established by the USEPA and the Chinese government. Demersal and near-benthic species accumulated more mercury than pelagic or mesopelagic species. The characteristics of mercury isotopes in wild-caught marine species differed in terms of vertical and horizontal distribution. Considering the known peripheral land sources of mercury (ΔHg ≈ 0), the mercury in seafood from the TSFG (ΔHg > 0) did not originate from anthropogenic emissions. The ratio of ΔHg and ΔHg (1.18 ± 0.03) suggested that the photoreduction of Hg (II) and the photo-degradation of MeHg equally contributed to mass-independent fractionation. Based on the values of ΔHg/δHg (1.18 ± 0.03), about 67% of the mercury in seawater had undergone microbial demethylation prior to methylation and entering the seafood. Additionally, the vertical distribution of ΔHg in seafood from different water depths implies that mercury input was in part caused by atmospheric deposition. Our results provide detailed information on the sources of mercury and its transfer in the food web in offshore fishing grounds.
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http://dx.doi.org/10.1007/s12011-021-02695-1DOI Listing
April 2021

Constructing Three-Dimensional Macroporous TiO Microspheres with Enhanced Pseudocapacitive Lithium Storage under Deep Discharging/Charging Conditions.

ACS Appl Mater Interfaces 2021 Apr 1;13(14):16528-16535. Epub 2021 Apr 1.

State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, International School of Materials Science and Engineering, Wuhan University of Technology, Wuhan 430070, P. R. China.

TiO has been intensively investigated as an anode material for lithium-ion batteries (LIBs) in 1.0-3.0 V ( Li/Li). However, it is a challenge to realize its theoretical capacity (336 mAh g) in this limited potential range. Extending the potential range below 1.0 V would increase its capacity but usually at the expense of its cyclic stability owing to the sluggish ionic diffusion and unsatisfactory structural stability. Here, three-dimensional (3D) macroporous TiO microspheres with interconnected pores and nanocrystalline thin walls have been constructed through a scalable template-assisted spray drying method to overcome these obstacles. When applied to LIBs, high and stable discharge capacity (300 mAh g at 0.1 A g) as well as superior cyclic stability (242 mAh g after 1000 cycles at 1.0 A g) can be achieved under deep discharging/charging conditions (0.01-3.0 V Li/Li). Furthermore, the 3D macroporous structure is well preserved under deep discharging/charging and the X-ray diffraction (XRD) patterns and Raman spectra reveal the dominant pseudocapacitive contribution at low potentials (0.01-1.0 V). This work not only develops a facile method to synthesize macroporous metal oxides but also provides insight into the lithium storage mechanism of TiO under deep discharging/charging conditions.
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http://dx.doi.org/10.1021/acsami.1c02411DOI Listing
April 2021

Upregulating hsa-miR-128a Increased the Effects of Pembrolizumab on Laryngeal Cancer Cells via the p53 Pathway.

Biomed Res Int 2021 18;2021:2342784. Epub 2021 Mar 18.

Department of Otolaryngology-Head and Neck Surgery, Eye and ENT Hospital of Fudan University, No. 83, Fenyang Road, Xuhui District, 200031 Shanghai, China.

Objectives: Recently, immunotherapy and microRNA have shown much more promises in oncology research, inspiring new hope for a cure for various malignancies. Specifically, the function and mechanisms of action of pembrolizumab have been investigated in many cancers, but not in laryngeal squamous cell carcinoma. The present study thus focused on the effect of hsa-miR-128a on pembrolizumab in laryngeal cancer cells as well as tried to elucidate the mechanisms that may mediate this effect.

Methods: Hep2 and AMC-HN8 cell lines were utilized to create stable cell lines that overexpressing hsa-miR-128a. Using the immunotherapy assay, the contribution of hsa-miR-128a to pembrolizumab sensitivity was evaluated. By performing the dual luciferase assay and quantitative real-time polymerase chain reaction, the possible mechanisms of hsa-miR-128a were identified.

Results: Hsa-miR-128a was overexpressed in laryngeal cancer cell lines successfully. The immunotherapy assay revealed that upregulating hsa-miR-128a augmented the effect of pembrolizumab. Moreover, hsa-miR-128a targeted BMI-1 and might played a role in the p53 pathway.

Conclusion: Hsa-miR-128a boosted the effect of pembrolizumab on laryngeal cancer cells, perhaps via the p53 pathway. Therefore, hsa-miR-128a might be a novel target in laryngeal cancer treatment.
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http://dx.doi.org/10.1155/2021/2342784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997759PMC
March 2021

Career choice and influential factors among medical students majoring in psychiatry in China.

BMC Med Educ 2021 Mar 25;21(1):183. Epub 2021 Mar 25.

Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), 51 Huayuan Bei Road, Beijing, 100191, China.

Background: The undergraduate program of psychiatry has been widely established in recent years to improve the education and recruitment of psychiatrists in China. We aim to investigate the career choice of medical students majoring in psychiatry in China and the influential factors.

Method: This multicenter study was conducted in 26 medical schools in China from May to October of 2019. Participants included 4610 medical students majoring in psychiatry and 3857 medical students majoring in clinical medicine. Multivariable logistic regression was used to investigate the influential factors of students' choices of psychiatry at matriculation and as a career.

Results: 44.08% of psychiatry majored students gave psychiatry as a first choice at matriculation, and 56.67% of them would choose psychiatry as a career, which was in sharp contrast to the proportion of clinical medicine majored students who would choose psychiatry as a career (0.69%). Personal interest (59.61%), suggestions from family members (27.96%), and experiencing mental problems (23.19%) were main reasons for choosing psychiatry major at matriculation. Personal interest (odds ratio [OR] = 2.12, 95% confidence interval [CI] = 1.87-2.40), experiencing a psychiatry clerkship (OR = 1.99, 95% CI = 1.28-3.08), being female (OR = 1.50, 95% CI = 1.30-1.68), experiencing mental problems (OR = 1.33, 95% CI = 1.28-1.56), and suggestions from family members (OR = 1.25, 95% CI = 1.08-1.46) correlated positively with students' choice of psychiatry as career. Students who lacked psychiatry knowledge (OR = 0.49, 95% CI = 0.29-0.85) or chose psychiatry because of lower admission scores (OR = 0.80, 95% CI = 0.63-0.97) were less likely to choose psychiatry as a career.

Conclusion: More than half of psychiatry majored medical school students planned to choose psychiatry as their career, whereas very few students in the clinic medicine major would make this choice. Increasing students' interest in psychiatry, strengthening psychiatry clerkships, and popularizing psychiatric knowledge are modifiable factors to increase the psychiatry career intention. The extent to which medical students' attitudes toward psychiatry can be changed through medical school education and greater exposure to psychiatry will need further investigation.
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http://dx.doi.org/10.1186/s12909-021-02622-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992123PMC
March 2021

Effect of basal forebrain somatostatin and parvalbumin neurons in propofol and isoflurane anesthesia.

CNS Neurosci Ther 2021 Mar 25. Epub 2021 Mar 25.

Key Laboratory of Brain Science, Zunyi Medical University, Zunyi, China.

Aims: The basal forebrain (BF) plays an essential role in wakefulness and cognition. Two subtypes of BF gamma-aminobutyric acid (GABA) neurons, including somatostatin-expressing (GABA ) and parvalbumin-positive (GABA ) neurons, function differently in mediating the natural sleep-wake cycle. Since the loss of consciousness induced by general anesthesia and the natural sleep-wake cycle probably share similar mechanisms, it is important to clarify the accurate roles of these neurons in general anesthesia procedure.

Methods: Based on two transgenic mouse lines expressing SOM-IRES-Cre and PV-IRES-Cre, we used a combination of genetic activation, inactivation, and chronic ablation approaches to further explore the behavioral and electroencephalography (EEG) roles of BF and BF neurons in general anesthesia. After a single intravenous injection of propofol and the induction and recovery times of isoflurane anesthesia, the anesthesia time was compared. The changes in cortical EEG under different conditions were also compared.

Results: Activation of BF GABA neurons facilitates both the propofol and isoflurane anesthesia, manifesting as a longer anesthesia duration time with propofol anesthesia and a fast induction time and longer recovery time with isoflurane anesthesia. Moreover, BF GABA -activated mice displayed a greater suppression of cortical electrical activity during anesthesia, showing an increase in δ power bands or a simultaneous decrease in high-frequency power bands. However, only a limited and nuanced effect on propofol and isoflurane anesthesia was observed with the manipulated BF GABA neurons.

Conclusions: Our results suggested that BF GABA neurons play a critical role in propofol and isoflurane general anesthesia, while BF GABA neurons appeared to have little effect.
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http://dx.doi.org/10.1111/cns.13635DOI Listing
March 2021

The CK1δ/ε-AES axis regulates tumorigenesis and metastasis in colorectal cancer.

Theranostics 2021 4;11(9):4421-4435. Epub 2021 Mar 4.

Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Cancer Research Center, Department of Pharmacology, Shenzhen University Health Science Center, Shenzhen 518055, China.

Amino-terminal enhancer of split (AES) has been identified as a tumor and metastasis suppressor in some cancers including colorectal cancer (CRC), but very little is known about the regulation of AES expression. Bioinformatics analysis was used to investigate the expression patterns of AES, CK1δ and CK1ε. The co-immunoprecipitation, GST pull-down, Western Blot, real-time PCR and immunohistochemistry were performed to study the mechanism underlying the regulation of AES expression by CK1δ/ε. The biological function was assessed by colony formation, transwell, sphere formation, tumor organoids, tumor metastasis model and patient-derived colorectal tumor xenografts (PDTX) model. A strong inverse relationship was observed between the expression of AES and the expression of CK1δ/ε. Mechanically, AES could interact with CK1δ/ε and SKP2 using its Q domain. SKP2 mediated the ubiquitination and degradation of AES in a CK1δ/ε-dependent manner. CK1δ/ε phosphorylated AES at Ser121 and accelerated the SKP2-mediated ubiquitination and degradation of AES. In colon cancer cells, CK1δ/ε antagonized the effect of wild-type AES but not that of its mutant (S121A) on Wnt and Notch signaling, leading to an increase in the expression of Wnt target genes and Notch target genes. By downregulating the expression of AES, CK1δ/ε enhanced anchorage-independent growth, migration, invasion and sphere formation in colon cancer cells. CK1δ/ε also promoted the growth of APC colorectal tumor organoids and liver metastasis in colon cancer mouse models through the regulation of AES degradation. Furthermore, CK1 inhibitor SR3029 treatment suppressed tumor growth via stabilizing AES in APC colorectal tumor organoids and patient-derived colorectal tumor xenografts (PDTX). Our results revealed that the CK1δ/ε-AES axis is important for CRC tumorigenesis and metastasis, and targeted inhibition of this axis may be a potential therapeutic strategy for CRC.
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http://dx.doi.org/10.7150/thno.53901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7977458PMC
March 2021

Early-stage dynamics of chloride ion-pumping rhodopsin revealed by a femtosecond X-ray laser.

Proc Natl Acad Sci U S A 2021 Mar;118(13)

Complex Systems Division, Beijing Computational Science Research Center, Haidian, 100193 Beijing, People's Republic of China;

Chloride ion-pumping rhodopsin (ClR) in some marine bacteria utilizes light energy to actively transport Cl into cells. How the ClR initiates the transport is elusive. Here, we show the dynamics of ion transport observed with time-resolved serial femtosecond (fs) crystallography using the Linac Coherent Light Source. X-ray pulses captured structural changes in ClR upon flash illumination with a 550 nm fs-pumping laser. High-resolution structures for five time points (dark to 100 ps after flashing) reveal complex and coordinated dynamics comprising retinal isomerization, water molecule rearrangement, and conformational changes of various residues. Combining data from time-resolved spectroscopy experiments and molecular dynamics simulations, this study reveals that the chloride ion close to the Schiff base undergoes a dissociation-diffusion process upon light-triggered retinal isomerization.
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http://dx.doi.org/10.1073/pnas.2020486118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020794PMC
March 2021

Lateral Habenula Glutamatergic Neurons Modulate Isoflurane Anesthesia in Mice.

Front Mol Neurosci 2021 4;14:628996. Epub 2021 Mar 4.

Department of Anesthesiology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Since their introduction in the 1840s, one of the largest mysteries of modern anesthesia are how general anesthetics create the state of reversible loss of consciousness. Increasing researchers have shown that neural pathways that regulate endogenous sleep-wake systems are also involved in general anesthesia. Recently, the Lateral Habenula (LHb) was considered as a hot spot for both natural sleep-wake and propofol-induced sedation; however, the role of the LHb and related pathways in the isoflurane-induced unconsciousness has yet to be identified. Here, using real-time calcium fiber photometry recordings , we found that isoflurane reversibly increased the activity of LHb glutamatergic neurons. Then, we selectively ablated LHb glutamatergic neurons in Vglut2-cre mice, which caused a longer induction time and less recovery time along with a decrease in delta-band power in mice under isoflurane anesthesia. Furthermore, using a chemogenetic approach to specifically activate LHb glutamatergic neurons shortened the induction time and prolonged the recovery time in mice under isoflurane anesthesia with an increase in delta-band power. In contrast, chemogenetic inhibition of LHb glutamatergic neurons was very similar to the effects of selective lesions of LHb glutamatergic neurons. Finally, optogenetic activation of LHb glutamatergic neurons or the synaptic terminals of LHb glutamatergic neurons in the rostromedial tegmental nucleus (RMTg) produced a hypnosis-promoting effect in isoflurane anesthesia with an increase in slow wave activity. Our results suggest that LHb glutamatergic neurons and pathway are vital in modulating isoflurane anesthesia.
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http://dx.doi.org/10.3389/fnmol.2021.628996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969819PMC
March 2021

The effect of the area proportion of the metastatic lesion within the central metastatic lymph node on response to therapy in papillary thyroid carcinoma.

Oncol Lett 2021 Apr 12;21(4):284. Epub 2021 Feb 12.

Department of Head and Neck Surgery, Affiliated Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Zhejiang, Hangzhou 310016, P.R. China.

Lymph node (LN) metastasis has been strongly associated with locoregional recurrence and decreased survival time of patients with papillary thyroid carcinoma (PTC). Although the characteristics of the metastatic LNs (mLN) have been determined, including size, number, micro-metastasis and extra-nodal extension (ENE), further analysis is warranted. The present study introduced a new parameter known as the area proportion of the metastatic lesion within the central mLNs (APmCLN). The objective was to evaluate the impact of the APmCLN on response to therapy in patients with PTC. In total, 355 patients with PTC treated with total thyroidectomy and neck dissection, post-operative radioactive iodine and thyroid-stimulating hormone suppression were retrospectively studied. The patients were classified into two groups: Group A (APmCLN ≤75%) and group B (APmCLN >75%). The association of various clinicopathological characteristics between these two groups was investigated. Univariate and multivariate analyses were used to evaluate risk factors associated with a non-Excellent response to therapy and recurrence-free survival (RFS). The analysis showed that APmCLN >75% was significantly associated with extra-thyroidal extension, clinically apparent nodes (cN1), pathological N1b (pN1b), ENE, greater number and larger size of central mLN and larger size of the central LN metastatic lesion. Furthermore, it was reported that chronic lymphocytic thyroiditis, larger central mLN size and APmCLN >75% were independent risk factors for a non-excellent response to therapy. Finally, it was determined that the rate of excellent response to therapy was significantly higher in pathological N1 (pN1) patients with APmCLN ≤75% (108/144, 75.0%) compared with patients with APmCLN >75% (27/47, 57.4%) (P=0.022). However, there was no significant difference (P=0.247) between patients with APmCLN ≤75% and pN0 (132/164, 80.5%). RFS was 89.4% in patients with pN1-APmCLN >75%, whereas those with pN1-APmCLN ≤75% and pN0 did not experience a relapse. Patients with PTC with APmCLN >75% should be regarded as high-risk and may require more aggressive treatment and careful follow-up.
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http://dx.doi.org/10.3892/ol.2021.12545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905529PMC
April 2021

The effect of the area proportion of the metastatic lesion within the central metastatic lymph node on response to therapy in papillary thyroid carcinoma.

Oncol Lett 2021 Apr 12;21(4):284. Epub 2021 Feb 12.

Department of Head and Neck Surgery, Affiliated Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Zhejiang, Hangzhou 310016, P.R. China.

Lymph node (LN) metastasis has been strongly associated with locoregional recurrence and decreased survival time of patients with papillary thyroid carcinoma (PTC). Although the characteristics of the metastatic LNs (mLN) have been determined, including size, number, micro-metastasis and extra-nodal extension (ENE), further analysis is warranted. The present study introduced a new parameter known as the area proportion of the metastatic lesion within the central mLNs (APmCLN). The objective was to evaluate the impact of the APmCLN on response to therapy in patients with PTC. In total, 355 patients with PTC treated with total thyroidectomy and neck dissection, post-operative radioactive iodine and thyroid-stimulating hormone suppression were retrospectively studied. The patients were classified into two groups: Group A (APmCLN ≤75%) and group B (APmCLN >75%). The association of various clinicopathological characteristics between these two groups was investigated. Univariate and multivariate analyses were used to evaluate risk factors associated with a non-Excellent response to therapy and recurrence-free survival (RFS). The analysis showed that APmCLN >75% was significantly associated with extra-thyroidal extension, clinically apparent nodes (cN1), pathological N1b (pN1b), ENE, greater number and larger size of central mLN and larger size of the central LN metastatic lesion. Furthermore, it was reported that chronic lymphocytic thyroiditis, larger central mLN size and APmCLN >75% were independent risk factors for a non-excellent response to therapy. Finally, it was determined that the rate of excellent response to therapy was significantly higher in pathological N1 (pN1) patients with APmCLN ≤75% (108/144, 75.0%) compared with patients with APmCLN >75% (27/47, 57.4%) (P=0.022). However, there was no significant difference (P=0.247) between patients with APmCLN ≤75% and pN0 (132/164, 80.5%). RFS was 89.4% in patients with pN1-APmCLN >75%, whereas those with pN1-APmCLN ≤75% and pN0 did not experience a relapse. Patients with PTC with APmCLN >75% should be regarded as high-risk and may require more aggressive treatment and careful follow-up.
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http://dx.doi.org/10.3892/ol.2021.12545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905529PMC
April 2021

Changes in psychotic-like experiences and related influential factors in technical secondary school and college students during COVID-19.

Schizophr Res 2021 Mar 13;231:3-9. Epub 2021 Mar 13.

Department of Social Psychiatry, the Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, China. Electronic address:

Objective: Although students have been found to be at high risk of distress during the COVID-19 pandemic, little is known about the pandemic's impact on psychotic-like experiences (PLEs). We conducted a study in technical secondary school and college students before and during the pandemic to explore changes in PLEs and relevant influential factors.

Methods: A total of 938 students completed both waves of the survey through electronic questionnaires. PLEs were assessed using the 15-item Positive Subscale of the Community Assessment of Psychic Experiences (CAPE-P15). Childhood trauma, perceived stress, resilience, and demographic factors were evaluated at baseline, and psychological status was measured during the pandemic.

Results: The overall CAPE-P15 scores significantly decreased during the pandemic. Students with persistent PLEs showed the most severe COVID-19 related psychological symptoms, followed by new-onset and remitted individuals; those without PLEs exhibited the mildest symptoms (all p < .001). A single parent family (OR = 4.707), more childhood trauma (OR = 1.056), and a higher family income (OR = 1.658) were predictive of new-onset PLEs during the pandemic, while better resilience was a protective factor, associated with remission of previous PLEs (OR = 0.932).

Conclusions: Despite a downward trend in the prevalence of PLEs during the pandemic, PLEs predict greater serious psychological impact due to COVID-19, especially for students with persistent PLEs. Interventions that cultivate students' resilience are urgently needed to reduce PLEs and improve mental health, especially for students from single parent households or those who have experienced childhood trauma.
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http://dx.doi.org/10.1016/j.schres.2021.02.015DOI Listing
March 2021

Design of multi-shelled hollow Cr2O3 spheres for metabolic fingerprinting.

Angew Chem Int Ed Engl 2021 Mar 15. Epub 2021 Mar 15.

Wuhan University of Technology, State Key Laboratory of Advanced Technology and Materials Synthesis and Processing, CHINA.

Schizophrenia (SZ) detection enables effective treatment to improve the clinical outcome, but objective and reliable SZ diagnostics are still limited. An ideal diagnosis of SZ suited for robust clinical screening must address detection throughput, low invasiveness, and diagnosis accuracy. Herein, we built a multi-shelled hollow Cr 2 O 3 spheres (MHCSs) assisted laser desorption/ionization mass spectrometry (LDI MS) platform for the direct metabolic profiling of biofluids towards SZ diagnostics. The MHCSs displayed strong light absorption for enhanced ionization and microscale surface roughness with stability for the effective LDI of metabolites. We profiled urine and serum metabolites (~ 1 μL) with the enhanced LDI efficacy in seconds. We discriminated SZ patients (SZs) from healthy controls (HCs) with the highest area under the curve (AUC) value of 1.000 for the blind test. We identified four compounds with optimal diagnostic power as a simplified metabolite panel for SZ and demonstrated the metabolite quantification for clinic use. Our approach accelerates the growth of new platforms toward a precision diagnosis in the near future.
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http://dx.doi.org/10.1002/anie.202101007DOI Listing
March 2021

Design of multi-shelled hollow Cr2O3 spheres for metabolic fingerprinting.

Angew Chem Int Ed Engl 2021 Mar 15. Epub 2021 Mar 15.

Wuhan University of Technology, State Key Laboratory of Advanced Technology and Materials Synthesis and Processing, CHINA.

Schizophrenia (SZ) detection enables effective treatment to improve the clinical outcome, but objective and reliable SZ diagnostics are still limited. An ideal diagnosis of SZ suited for robust clinical screening must address detection throughput, low invasiveness, and diagnosis accuracy. Herein, we built a multi-shelled hollow Cr 2 O 3 spheres (MHCSs) assisted laser desorption/ionization mass spectrometry (LDI MS) platform for the direct metabolic profiling of biofluids towards SZ diagnostics. The MHCSs displayed strong light absorption for enhanced ionization and microscale surface roughness with stability for the effective LDI of metabolites. We profiled urine and serum metabolites (~ 1 μL) with the enhanced LDI efficacy in seconds. We discriminated SZ patients (SZs) from healthy controls (HCs) with the highest area under the curve (AUC) value of 1.000 for the blind test. We identified four compounds with optimal diagnostic power as a simplified metabolite panel for SZ and demonstrated the metabolite quantification for clinic use. Our approach accelerates the growth of new platforms toward a precision diagnosis in the near future.
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http://dx.doi.org/10.1002/anie.202101007DOI Listing
March 2021

Enhancing Osseointegration of TC4 Alloy by Surficial Activation Through Biomineralization Method.

Front Bioeng Biotechnol 2021 23;9:639835. Epub 2021 Feb 23.

Department of Orthopaedics, The Sixth Affiliated People's Hospital, Shanghai Jiao Tong University, Shanghai, China.

Titanium (Ti) alloys have been applied to biomedical implants for a long time. Although Ti alloys are biocompatible, efforts have been continuously made to improve their bone conductivity and osteogenesis for enhancing their performance. Silk fibroin (SF) is a natural biomaterial with excellent biomedical and mechanical properties, and hydroxyapatite (HAP) nanocomposites derived from SF are promising for producing "artificial bone" owing to their biomedical applicability and strong mechanical functions. Therefore, we built an SF coating on the surface of Ti-6Al-4V alloy, and then the incubated SF-coated Ti alloy were immersed in simulated body fluid to induce mineral deposition of HAP on the alloys. The results from Scanning Electron Microscopy (SEM), X-ray Diffraction (XRD) analysis, and Attenuated Total Reflection-Fourier Transform Infrared Spectroscopy (ATR-FTIR) confirmed the deposition of a mineral layer on the SF film surface. The proliferation, adhesion, and differentiation of MG-63 were tested, along with the BMP-2, COX-2, and OPG expression and protein content in the MG-63. Both Ti + SF and Ti + SF + HAP groups exhibited significantly better performance than a control Ti group with regard to the cell adhesion, cell proliferation, and protein expression. Furthermore, the hybrid layer comprising HAP and SF delivered more significant improvement of the osseointegration than the SF alone. It is hoped that the proposed methods can be used for constructing modified surfaces on Ti alloys, as they endowed the implants with good osteogenic potential.
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http://dx.doi.org/10.3389/fbioe.2021.639835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940542PMC
February 2021

The optimal number of embryo cells for effective pregnancy and decrease of multiple pregnancy rate in frozen-thawed embryo transfer.

Hum Cell 2021 Mar 10. Epub 2021 Mar 10.

Department of Reproduction Medicine, The Second Hospital of Hebei Medical University, 215 Western Heping Road, Shijiazhuang, 050011, Hebei Province, China.

To investigate the effect of the number of embryo cells on the clinical outcome of frozen-thawed embryo transfer and explore the optimal policy for decreases of multiple pregnancy rate, patients who experienced day 3 vitrified double frozen-thawed embryo transfer were retrospectively analyzed. According to the number of embryonic cells in each pre-frozen embryo, the patients were divided into six groups: 8C (two 8-cell embryos), 8C- < 8C (one 8-cell embryo and one under-8-cell embryo), 8C- > 8C (one 8-cell embryo and one over-8-cell embryo), < 8C (two under-8-cell embryos), < 8C- > 8C (one under-8-cell embryo and one over-8-cell embryo), and > 8C (two over-8-cell embryos). The clinical data were analyzed. The classification decision tree was used to analyze the optimal transfer strategy. A total of 2184 cycles of day 3 vitrified double frozen-thawed embryo transfer were enrolled. In day 3 double frozen-thawed embryo cycles, the 8C group and 8C- > 8C group had significantly (P < 0.05) higher pregnancy and multiple pregnancy rates than the other groups. No significant (P > 0.05) difference existed in the pregnancy rate and live birth rate between the 8C- < 8C group, 8C group and 8C- > 8C group, but the implantation rate and multiple pregnancy rate in the 8C- < 8C group were significantly (P < 0.05) lower than in the other two groups. Compared with the multiple pregnancy rate of all cycles, the cycles in two branches showed significantly (P < 0.05) higher multiple pregnancy rates (≤ 29 years old: 8C / 8C- > 8C; 29 < age ≤ 36 years for the first transfer: 8C / 8C- < 8C / 8C- > 8C, one branch showed similar rate (≤ 29 years old: 8C / 8C- > 8C) for the first transfer, and the remaining four branches demonstrated significantly (P < 0.05) lower rates. The clinical pregnancy rates before and after optimization were 51.0% vs 50.5%, and the multiple pregnancy rates were 38.5% vs 16.9%. In conclusion, the number of pre-frozen embryonic cells is an important factor affecting the clinical outcome of frozen-thawed embryo transfer in day 3 double good embryos frozen-thawed cycles. The age of patient, number of embryo cells, and the first time of transfer are the most valuable parameters for prediction. For women ≤ 29 years old, the single embryo transfer (SET) strategy was to choose an embryo ≥ 8 cells, and for women with < 29 age ≤ 36 years old, the SET strategy in the first transfer was to choose an embryo ≥ 8 cells.
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http://dx.doi.org/10.1007/s13577-021-00516-0DOI Listing
March 2021

Efficacy and Safety of Long-Term Antithrombotic Strategies in Patients With Chronic Coronary Syndrome: A Network Meta-analysis of Randomized Controlled Trials.

J Am Heart Assoc 2021 Mar 6;10(6):e019184. Epub 2021 Mar 6.

The Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine Hangzhou Zhejiang China.

Background Long-term antithrombotic strategies for patients with chronic coronary syndrome with high-risk factors represent an important treatment dilemma in clinical practice. Our aim was to conduct a network meta-analysis to evaluate the efficacy and safety of long-term antithrombotic strategies in patients with chronic coronary syndrome. Methods and Results Four randomized studies were included (n=75167; THEMIS [Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study], COMPASS [Cardiovascular Outcomes for People Using Anticoagulation Strategies], PEGASUS-TIMI 54 [Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54], and DAPT [Dual Anti-platelet Therapy]). The odds ratios (ORs) and 95% CIs) were calculated as the measure of effect size. The results of the network meta-analysis showed that, compared with aspirin monotherapy, the ORs for trial-defined major adverse cardiovascular and cerebrovascular events were 0.86; (95% CI, 0.80-0.93) for ticagrelor plus aspirin, 0.89 (95% CI, 0.78-1.02) for rivaroxaban monotherapy, 0.74 (95% CI, 0.64-0.85) for rivaroxaban plus aspirin, and 0.72 (95% CI, 0.60,-0.86) for thienopyridine plus aspirin. Compared with aspirin monotherapy, the ORs for trial-defined major bleeding were 2.15 (95% CI, 1.78-2.59]) for ticagrelor plus aspirin, 1.51 (95% CI, 1.23-1.85) for rivaroxaban monotherapy, and 1.68 (95% CI, 1.37-2.05) for rivaroxaban plus aspirin. For death from any cause, the improvement effect of rivaroxaban plus aspirin was detected versus aspirin monotherapy (OR, 0.76; 95% CI, 0.65-0.90), ticagrelor plus aspirin (OR, 0.79; 95% CI, 0.66-0.95), rivaroxaban monotherapy (OR, 0.82; 95% CI, 0.69-0.97), and thienopyridine plus aspirin (OR, 0.58; 95% CI, 0.41-0.82) regimens. Conclusions All antithrombotic strategies combined with aspirin significantly reduced the incidence of major adverse cardiovascular and cerebrovascular events and increased the risk of major bleeding compared with aspirin monotherapy. Considering the outcomes of all ischemic and bleeding events and all-cause mortality, rivaroxaban plus aspirin appears to be the preferred long-term antithrombotic regimen for patients with chronic coronary syndrome and high-risk factors.
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http://dx.doi.org/10.1161/JAHA.120.019184DOI Listing
March 2021

Long non-coding RNA THRIL inhibits miRNA-24-3p to upregulate neuropilin-1 to aggravate cerebral ischemia-reperfusion injury through regulating the nuclear factor κB p65 signaling.

Aging (Albany NY) 2021 Mar 6;13(6):9071-9084. Epub 2021 Mar 6.

Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.

Purpose: The aim of this study was to investigate the role of the tumor necrosis factor and HNRNPL related immunoregulatory long non-coding RNA (THRIL) in cerebral ischemia-reperfusion injury.

Methods: A rat middle cerebral artery occlusion/ischemia-reperfusion (MCAO/IR) model and an oxygen glucose deprivation/reoxygenation (OGD/R) cell model were constructed. THRIL was knocked down using siTHRIL. Neurological deficit score was detected based on the criteria of Zea-Longa. Brain region 2,3,5-Triphenyltetrazolium (TTC) staining and quantitative analysis of cerebral infarction volume, RT-qPCR, and fluorescence immunostaining were performed for assessing THRIL expression. MTT assay was used to detect the cell proliferation ability after transfection, TUNEL assay was applied to detect apoptosis, and western blot and ELISA detected related protein expression. A dual luciferase reporter system and RIP assay were used to confirm the target relationship.

Results: THRIL was upregulated in both and models of brain ischemia-reperfusion injury. Knockdown of THRIL attenuated OGD/R neuronal apoptosis and OGD/R-induced inflammation. THRIL targeted and regulated the expression of miR-24-3p/neuropilin-1 (NRP1) axis. THRIL silencing significantly improved the neurological functioning of rats in the MCAO/R model by miR-24-3p/NRP1/NF-κB p65 signaling pathway.

Conclusion: THRIL could aggravate cerebral ischemia-reperfusion injury by competitively binding to miR-24-3p to promote the upregulation of NRP1 and further promoted the activation of the NF-κB p65 signaling pathway.
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http://dx.doi.org/10.18632/aging.202762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034910PMC
March 2021

Preoperative tracheotomy as reflection of tumor size impacting oncologic outcomes of patients with advanced stage glottic carcinoma.

Eur Arch Otorhinolaryngol 2021 Mar 6. Epub 2021 Mar 6.

Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, 200031, China.

Purpose: The aim of this study was to evaluate the influence of preoperative tracheotomy on oncologic outcomes of advanced stage glottic carcinoma patients, and to explore the potential reason.

Methods: We retrospectively analyzed 413 consecutive advanced stage glottic carcinoma patients from January 2005 to December 2010. The correlation of preoperative tracheotomy and potential impacting factor of tumor size involving tumor diameter and tumor area with overall survival (OS) and disease-free survival (DFS) was fully assessed.

Results: Our cohort consisted of 302 (73.1%) patients with T3 and 111 (26.9%) patients with T4, and 98 (23.7%) patients received preoperative tracheotomy. The OS and DFS rates of patients receiving preoperative tracheotomy were worse than those without (5-year OS: 49.3% versus 69.8%; 5-year DFS: 45.3% versus 61.0%). The mean tumor diameter and tumor area of patients with preoperative tracheotomy were greater than those without (3.3 cm versus 2.4 cm, 8.9 cm versus 4.7 cm). The optimal cutoff values of tumor diameter and tumor area for tracheotomy were 2.85 cm and 6.64 cm. Tumor diameter and tumor area were correlated with tracheotomy intervention. Furthermore, when considering the potential effect of tumor area in multivariate model, we found that it was a significant factor in survival outcomes but variable of preoperative tracheotomy was not.

Conclusion: This study indicates that tumor size is correlated with preoperative tracheotomy, and tracheotomy intervention may be reflection from effect of great tumor size that is a true adverse factor influencing oncologic outcomes of advanced stage glottic carcinoma patients.
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http://dx.doi.org/10.1007/s00405-021-06721-9DOI Listing
March 2021

LncRNA BACE1-AS enhances the invasive and metastatic capacity of hepatocellular carcinoma cells through mediating miR-377-3p/CELF1 axis.

Life Sci 2021 Jun 2;275:119288. Epub 2021 Mar 2.

Department of General Surgery, BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, Jiangsu, China. Electronic address:

Aims: Hepatocellular carcinoma (HCC) is a malignant cancer that threatened human life seriously. Long non-coding RNA (lncRNA) BACE1-AS has been reported as a key regulator in tumorigenesis. Yet the specific correlation between BACE1-AS and HCC still needs further investigation. The primary purpose of our study is to reveal the exact correlation between BACE1-AS and HCC.

Main Methods: Bioinformatics via TCGA database revealed BACE1-AS closely related with HCC. qRT-PCR confirmed the abnormal BACE1-AS level in HCC tissues and cells. Databases prediction suggested that miR-377-3p might be a modulatory target of BACE1-AS and luciferase assay confirmed this hypothesis. Further study discovered that CELF1 also partook in the regulatory axis of BACE1-AS/miR-377-3p. Wound healing assays and transwell assays were utilized to investigate the impact of BACE1-AS, miR-377-3p and CELF1 in vitro. In vivo metastasis was examined by pulmonary metastasis model.

Key Findings: This study found that BACE1-AS was overexpressed in HCC tissues and cell lines. Knockdown of BACE1-AS could restrain HCC progression in vitro, and inhibit pulmonary metastasis in vivo. MiR-377-3p was negatively modulated by BACE1-AS in HCC tumor tissues and cells. MiR-377-3p up-regulation inhibited HCC cells migration and invasion via inactivating EMT process. Moreover, CELF1 was identified as a downstream regulator of miR-377-3p and served as an oncogene in HCC cells.

Significance: Our findings supported that lncRNA BACE1-AS was up-regulated in HCC, promoting invasion and metastasis of hepatocellular carcinoma cells by modulating miR-377-3p/CELF1 axis via contributing to EMT pathway. BACE1-AS could be a potential biomarker in HCC for future treatment.
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http://dx.doi.org/10.1016/j.lfs.2021.119288DOI Listing
June 2021

Correlations between Dual-Pathway White Matter Alterations and Language Impairment in Patients with Aphasia: A Systematic Review and Meta-analysis.

Neuropsychol Rev 2021 Mar 3. Epub 2021 Mar 3.

Department of Neurology & Brain Medical Centre, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, P. R. China.

While converging evidence suggests linguistic roles of white matter tracts, detailed associations between white matter alterations of dual pathways and language abilities remain unknown in aphasic patients. We aimed to verify language functions of dual-pathway tracts from specific domains and investigate the influence of moderators. PubMed, Web of Science, Embase, and CENTRAL were searched for studies published between January 1, 1985 and March 17, 2019. A meta-analysis of 46 studies including 1353 aphasic patients was performed by pooling correlation coefficients between linguistic domains and diffusion metrics of dual-pathway tracts. Among these tracts, the fractional anisotropy (FA) value of the left inferior fronto-occipital fasciculus predominated across most linguistic aspects, showing the strongest correlations with global severity, comprehension, naming and reading ability. The left uncinate fasciculus and inferior longitudinal fasciculus also showed significant FA - comprehension correlations. For syntactic processing, FA values of the left superior longitudinal fasciculus and arcuate fasciculus showed significant positive correlations. Meta-regression revealed no influence of etiology on FA - language correlations, while sex had a moderating effect on the FA - comprehension correlation of the arcuate fasciculus, and age influenced the FA - naming correlation in the superior longitudinal fasciculus. In conclusion, multifunctional characteristics of tracts were revealed in aphasic patients, including broad linguistic associations of the inferior fronto-occipital fasciculus, and repetition and syntactic involvement of the arcuate fasciculus. Language associations of the inferior longitudinal fasciculus and uncinate fasciculus were clarified regarding comprehension subdomains. The insignificant moderating effect of the etiology indicates damage of dual pathways is the common neural mechanism, while sex and age influence the correlation with comprehension and naming ability, respectively, in specific tracts.
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http://dx.doi.org/10.1007/s11065-021-09482-8DOI Listing
March 2021

A wave optics model for the effect of partial coherence on coherent diffractive imaging.

J Synchrotron Radiat 2021 Mar 14;28(Pt 2):499-504. Epub 2021 Jan 14.

Beijing Synchrotron Radiation Facility, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, People's Republic of China.

With the development of fourth-generation synchrotron sources, coherent diffractive imaging (CDI) will be a mainstream method for 3D structure determination at nanometre resolution. The partial coherence of incident X-rays plays a critical role in the reconstructed image quality. Here a wave optics model is proposed to analyze the effect of partial coherence on CDI for an actual beamline layout, based on the finite size of the source and the influence of the optics on the wavefront. Based on this model, the light field distribution at any plane, the coherence between any two points on this plane and CDI experiments can be simulated. The plane-wave CDI simulation result also shows that in order to reconstruct good image quality of complex samples the visibility of the interference fringes of any two points in the horizontal and vertical directions of the incident light field at the sample needs to be higher than 0.95.
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http://dx.doi.org/10.1107/S1600577520015684DOI Listing
March 2021