Publications by authors named "Zhiyin Yang"

10 Publications

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Comprehensive analysis of tumor microenvironment and identification of an immune signature to predict the prognosis and immunotherapeutic response in lung squamous cell carcinoma.

Ann Transl Med 2021 Apr;9(7):569

Department of Thoracic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Background: Tumor mutation burden (TMB) and immune microenvironment are important determinants of prognosis and immunotherapeutic efficacy for cancer patients. The aim of the present study was to develop an immune signature to effectively predict prognosis and immunotherapeutic response in patients with lung squamous cell carcinoma (LUSC).

Methods: TMB and immune microenvironment characteristics were comprehensively analyzed by multi-omics data in LUSC. The immune signature was further constructed and validated in multiple independent datasets by LASSO Cox regression analysis. Next, the value of immune signature in predicting the response of immunotherapy was evaluated. Finally, the possible mechanism of immune signature was also investigated.

Results: A novel immune signature based on 5 genes was constructed and validated to predict the prognosis of LUSC patients. These genes were filamin-C, Rho family GTPase 1, interleukin 4-induced gene-1, transglutaminase 2, and prostaglandin I2 synthase. High-risk patients had significantly poorer survival than low-risk patients. A nomogram was also developed based on the immune signature and tumor stage, which showed good application. Furthermore, we found that the immune signature had a significant correlation with immune checkpoint, microsatellite instability, tumor infiltrating lymphocytes, cytotoxic activity scores, and T-cell-inflamed score, suggesting low-risk patients are more likely to benefit from immunotherapy. Finally, functional enrichment and pathway analyses revealed several significantly enriched immune-related biological processes and metabolic pathways.

Conclusions: In the present study, we developed a novel immune signature that could predict prognosis and immunotherapeutic response in LUSC patients. The results not only help identify LUSC patients with poor survival, but also increase our understanding of the immune microenvironment and immunotherapy in LUSC.
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http://dx.doi.org/10.21037/atm-21-463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105790PMC
April 2021

Theoretical prediction on photoelectric and supramolecular properties of benzoquinone-tetrathiafulvalene macrocyclic molecules.

J Mol Model 2021 May 7;27(6):157. Epub 2021 May 7.

School of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou, 225002, Jiangsu, China.

Benzoquinone has the ability to serve as an electron acceptor, and tetrathiafulvalene has the ability to serve as an electron donor. Based on the facts above, this work creatively cycles the benzoquinone unit and the tetrathiafulvalene unit alternately into macrocyclic molecules, the cyclopolymers of benzoquinone-tetrafluorene (C[n]QTTF, n = 3~6). To explore their structure and properties, the M06-2X functional of density functional theory (DFT) with 6-311g(d) basis set was used to optimize the ground-state structures of C[n]QTTF. Based on the stable configurations of the ground states, the electronic structure property is analyzed systematically. The results show that these macrocyclic molecules have excellent electron transport capability and electrochemical activity. Then, the electron absorption spectra of each system are carried out by using time-dependent density functional theory (TD-DFT) at the M062X/6-311+G(d) level. It turns out that their maximum absorption wavelengths are all in the visible range. Further calculation suggests that C[n]QTTF can also be characterized with one-dimensional self-assembly, double-walled assembly, and the host-guest inclusion performance, based on which it gains a variety of supramolecular structures. In summary, the benzoquinone-tetrafluorofurene macrocyclic molecules predicted by DFT calculations may be of assistance to the potential applications in organic electronics and supramolecular chemistry.
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http://dx.doi.org/10.1007/s00894-021-04782-5DOI Listing
May 2021

MicroRNA‑92a promotes non‑small cell lung cancer cell growth by targeting tumor suppressor gene FBXW7.

Mol Med Rep 2020 Oct 28;22(4):2817-2825. Epub 2020 Jul 28.

Department of Thoracic Surgery, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 201999, P.R. China.

MicroRNA (miRNA/miR)‑92a has been identified as being significantly downregulated in non‑small cell lung cancer (NSCLC) tissues using a miRNA array. However, its biological function and molecular mechanisms in NSCLC have not been fully elucidated. The aim of the present study was to determine the role of miR‑92a in NSCLC and the mechanisms by which it affects NSCLC cells. The expression levels of miR‑92a in NSCLC tissues and cell lines were analyzed using reverse transcription‑quantitative PCR. Cell viability and cell apoptosis were determined using an MTT assay and flow cytometry, respectively. It was observed that miR‑92a was significantly upregulated in NSCLC tissues and cell lines. Inhibition of miR‑92a significantly suppressed viability of NSCLC cells, with concomitant downregulation of key proliferative genes, such as proliferating cell nuclear antigen and Ki‑67. miR‑92a downregulation induced apoptosis of NSCLC cells, as evidenced by flow cytometry and apoptosis‑related protein detection. Luciferase assays confirmed that miR‑92a could directly bind to the 3'‑untranslated region of tumor suppressor F‑box/WD repeat‑containing protein 7 (FBXW7) and suppress its translation. Furthermore, small interfering RNA‑mediated FBXW7 inhibition partially attenuated the tumor suppressive effect of an miR‑92a inhibitor on NSCLC cells. Collectively, these findings demonstrated that miR‑92a might function as an oncogene in NSCLC by regulating FBXW7. In conclusion, miR‑92a could serve as a potential therapeutic target in NSCLC treatment.
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http://dx.doi.org/10.3892/mmr.2020.11373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453619PMC
October 2020

Application of 460 nm visible light for the elimination of Candida albicans in vitro and in vivo.

Mol Med Rep 2018 Aug 20;18(2):2017-2026. Epub 2018 Jun 20.

Department of Burns and Plastic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201999, P.R. China.

The aim of the present study was to investigate the eradicating effects of 460 nm blue light (BL) on Candida albicans in vitro and in C. albicans‑infected skin wounds in a mouse model. In the present study, the antifungal effects of irradiation with BL on C. albicans in vitro and in vivo were investigated. C. albicans colonies and cell numbers were investigated using the spread plate method and flow cytometry respectively following treatment with BL irradiation. In order to determine whether BL can eradicate C. albicans cells within biofilms, an in vitro C. albicans biofilm model was established, and the effect of BL was subsequently investigated using a confocal laser scanning microscope and a Live/Dead staining kit. Furthermore, a mouse skin wound infection model infected with C. albicans was established. Wound healing rates and histological examinations were determined 0, 3, 7, 10 and 14 days post‑wounding. The results revealed that C. albicans was eradicated by BL in a dose‑dependent manner, with a minimum fluence of 60 J/cm2. Irradiation with BL almost completely eradicated C. albicans when the light fluence was 240 J/cm2. C. albicans inside biofilms was also eradicated and biofilms were destroyed following BL irradiation at 240 J/cm2. In addition, BL was revealed to significantly suppress C. albicans infection in vivo. Irradiation with BL promoted the wound healing of C. albicans infected‑skin wounds in a mouse model. In conclusion, the results of the present study demonstrated that 460 nm BL may eradicate planktonic and biofilm C. albicans in vitro, and represents a novel therapeutic strategy for the treatment of C. albicans infections in vivo.
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http://dx.doi.org/10.3892/mmr.2018.9196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6072199PMC
August 2018

Inhibition of IRF8 Negatively Regulates Macrophage Function and Impairs Cutaneous Wound Healing.

Inflammation 2017 Feb;40(1):68-78

Department of Burns and Plastic Surgery, Shanghai Ninth People's Hospital, Institute of Traumatic Medicine, Shanghai Jiao Tong University School of Medicine, 280 Mohe Road, Baoshan District, Shanghai, 201900, China.

The inflammatory response is essential for normal cutaneous wound healing. Macrophages, as critical inflammatory cells, coordinate inflammation and angiogenesis phases during wound healing. It has been reported that the transcription factor interferon regulatory factor 8 (IRF8), a member of the IRF family, plays a critical role in the development and function of macrophages and is associated with inflammation. However, the role of IRF8 in cutaneous wound healing and its underlying mechanism remain elusive. Through immunohistochemical (IHC) staining, we showed that IRF8 is involved in the wound repair process in mice and patients. Furthermore, we ascertain that the repression of IRF8 by small interfering RNA (siRNA) leads to delayed wound healing. To explore the mechanism by which IRF8 impacts wound healing, we observed its effect on macrophage-related mediators by IHC or real-time PCR. The results demonstrated that the inhibition of IRF8 decreases the mRNA expression of inflammatory mediators associated with M1 macrophage (il-1b, il-6, inos, and tnf-a) but no impact on M2 macrophage-related mediators (arg-1, mrc-1, and il-10) and the number of macrophages in the wounds. Furthermore, the inhibition of IRF8 induced apoptosis in the wounds. In summary, this study demonstrates that the down-regulation of IRF8 in the wound leads to impaired wound healing possibly through the regulation of macrophage function and apoptosis in skin wound.
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http://dx.doi.org/10.1007/s10753-016-0454-8DOI Listing
February 2017

Aberrant hypermethylation of aldehyde dehydrogenase 2 promoter upstream sequence in rats with experimental myocardial infarction.

Biomed Res Int 2015 5;2015:503692. Epub 2015 Jan 5.

Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China ; Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.

Background: Aldehyde dehydrogenase 2 (ALDH2) plays a crucial role in myocardial protection against ischemia. Downregulation of ALDH2 was evidenced after myocardial infarction and the underlying mechanism is not fully understood. DNA methylation can regulate gene transcription in epigenetic level. We thus hypothesized that DNA methylation may affect ALDH2 expression in myocardial infarction (MI).

Methods: MI was induced in Sprague-Dawley rats. MI border zone tissues were harvested at 1st week, 2nd week, and 3rd week after MI. Bisulfite sequencing PCR (BSP) was performed to detect the methylation levels of ALDH2 core promoter. Sequenom MassARRAY platform (MassARRAY) was used to examine the methylation levels of ALDH2 promoter upstream sequence. ALDH2 protein and mRNA expression were assayed by Western blot and real-time PCR, respectively.

Results: Compared with Sham group, ALDH2 protein and mRNA expression of MI groups was significantly downregulated. Compared with Sham group, DNA methylation level of CpG sites in ALDH2 promoter upstream sequence was significantly higher in MI groups in a time-dependent manner (CpG1, CpG2, and CpG7, P < 0.01). DNA methylation did not affect ALDH2 core promoter sequence during the progress of MI. No significant difference was detected in DNA methylation level of ALDH2 promoter upstream sequence among MI groups.

Conclusion: Aberrant hypermethylation of CpG sites in ALDH2 promoter upstream sequence is associated with myocardial ischemia injury and may partly result in ALDH2 downregulation after MI.
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http://dx.doi.org/10.1155/2015/503692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4299765PMC
October 2015

Acetaldehyde dehydrogenase 2 (ALDH2) deficiency exacerbates pressure overload-induced cardiac dysfunction by inhibiting Beclin-1 dependent autophagy pathway.

Biochim Biophys Acta 2015 Feb 30;1852(2):310-8. Epub 2014 Jul 30.

Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China; Institute of Biomedical Science, Fudan University, Shanghai 200032, China.

Mitochondrial aldehyde dehydrogenase 2 (ALDH2) was demonstrated to play cardioprotective roles in cardiovascular diseases. Nonetheless, little is known about the roles and mechanisms of ALDH2 in pressure overload-induced cardiac damages. In this study, we revealed that ALDH2 deficiency overtly exacerbated transverse aortic constriction (TAC)-induced cardiac dysfunction. Cardiomyocyte enlargement was observed in both WT and ALDH2-/- mice in HE-stained myocardial tissue samples at 8 weeks post TAC surgery. Mitochondrial morphology and structure were also significantly damaged post TAC surgery and the changes were aggravated in ALDH2-/- TAC hearts. ALDH2 deficiency also depressed myocardial autophagy in hearts at 8 weeks post TAC surgery with a potential mechanism of repressing the expression of Beclin-1 and promoting the interaction between Bcl-2 and Beclin-1. These data indicate that ALDH2 deficiency exacerbates the pressure overload induced cardiac dysfunction partly by inhibiting Beclin-1 dependent autophagy pathway. This article is part of a Special Issue entitled: Autophagy and protein quality control in cardiometabolic diseases.
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http://dx.doi.org/10.1016/j.bbadis.2014.07.014DOI Listing
February 2015

Mechanisms of behavior modification in clinical behavioral medicine in China.

Int J Behav Med 2014 Aug;21(4):580-3

Shandong Key Laboratory of Behavioral Medicine, Jining Medical University, No. 16 Hehua Road, Jining Beihu New District, Shandong, 272067, China,

Background: Behavior modification, as the core of clinical behavioral medicine, is often used in clinical settings.

Purpose: We seek to summarize behavior modification techniques that are commonly used in clinical practice of behavioral medicine in China and discuss possible biobehavioral mechanisms.

Methods: We reviewed common behavior modification techniques in clinical settings in China, and we reviewed studies that explored possible biobehavioral mechanisms.

Results: Commonly used clinical approaches of behavior modification in China include behavior therapy, cognitive therapy, cognitive-behavioral therapy, health education, behavior management, behavioral relaxation training, stress management intervention, desensitization therapy, biofeedback therapy, and music therapy. These techniques have been applied in the clinical treatment of a variety of diseases, such as chronic diseases, psychosomatic diseases, and psychological disorders. The biobehavioral mechanisms of these techniques involve the autonomic nervous system, neuroendocrine system, neurobiochemistry, and neuroplasticity.

Conclusion: Behavior modification techniques are commonly used in the treatment of a variety of somatic and psychological disorders in China. Multiple biobehavioral mechanisms are involved in successful behavior modification.
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http://dx.doi.org/10.1007/s12529-014-9405-7DOI Listing
August 2014

A1180V of cardiac sodium channel gene (SCN5A): is it a risk factor for dilated cardiomyopathy or just a common variant in Han Chinese?

Dis Markers 2013 20;35(5):531-5. Epub 2013 Oct 20.

Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China ; Department of Cardiology, Shandong University, Jinan, Shandong 250012, China.

Our previous study of a Chinese family with dilated cardiomyopathy (DCM) suggested that A1180V of the cardiac sodium channel gene (SCN5A) was associated with the disease within this family. According to data deposited in dbSNP, however, A1180V has been found in some small samples of the Asian population. In this study, we followed up the affected pedigree and expanded the investigation of the prevalence of A1180V in 460 unrelated healthy Han Chinese. Besides, we searched and analyzed it in other database as well. During the follow-up period, 1 A1180V carrier's condition deteriorated a lot, and another 4 carriers progressed to DCM or atrioventricular block (AVB). We also found that the A1180V was absent among the 460 individuals (0%, 0/460), and the carrier frequency of A1180V among Chinese was about 0.51% obtained from the 1000 genome project. In conclusion, our finding suggests that A1180V is a potential risk factor for DCM, and it is extremely rare among Healthy Han Chinese.
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http://dx.doi.org/10.1155/2013/659528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3817650PMC
June 2014

Molecular and clinical characterization of a novel SCN5A mutation associated with atrioventricular block and dilated cardiomyopathy.

Circ Arrhythm Electrophysiol 2008 Jun 30;1(2):83-92. Epub 2008 Apr 30.

Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.

Background: Increased susceptibility to dilated cardiomyopathy has been observed in patients carrying mutations in the SCN5A gene, but the underlying mechanism remains unclear. In this study, we identified and characterized, both in vitro and clinically, an SCN5A mutation associated with familial progressive atrioventricular block of adult onset and dilated cardiomyopathy in a Chinese family.

Methods And Results: Among 32 family members, 5 were initially diagnosed with atrioventricular block after age 30; 4 were studied, 3 of whom later developed dilated cardiomyopathy. We found a heterozygous single-nucleotide mutation resulting in an amino acid substitution (A1180V) in all studied patients and in 6 other younger unaffected members but not in 200 control chromosomes. When expressed with the beta1 subunit, the mutated channels exhibited a -4.5-mV shift of inactivation with slower recovery leading to a rate-dependent Na(+) current reduction and a moderate increase in late Na(+) current. Clinical study revealed that although QRS duration decreased with increasing heart rate in noncarrier family members, this change was blunted in unaffected carriers whose ECG and heart function were normal. Resting corrected QT interval of unaffected carriers was significantly longer than that of noncarriers, even though it was still within the normal range.

Conclusions: A1180V expresses a mild Na(+) channel phenotype in vitro and a corresponding clinical phenotype in unaffected mutation carriers, implying that A1180V caused structural heart disease in affected carriers by disturbing Na(+) influx and, hence, cellular Na(+) homeostasis. The high penetrance of A1180V suggests this phenotype as a high risk factor for dilated cardiomyopathy with preceding atrioventricular block.
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http://dx.doi.org/10.1161/CIRCEP.107.750752DOI Listing
June 2008