Publications by authors named "Zhaoyan Wang"

101 Publications

[Perioperative airway management of infantile subglottic hemangioma].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2021 Jun;35(6):501-504;510

Department of Anesthesiology,Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine.

To investigate the relevant influencing factors for perioperative airway events of infantile subglottic hemangioma, and to further discuss the strategies of perioperative airway management. A total of 36 infants with subglottic hemangioma that had no response to the drug therapy and underwent surgical treatment from July 2007 to April 2017 were enrolled. The relevant influencing factors, including gender, age, birth weight, age of onset, degree of tracheal stenosis and histories of underlying diseases(congenital heart disease and respiratory disease), were also recorded simultaneously. Intraoperative SpO₂ decline, intraoperative emergency tracheal intubation, intraoperative emergency tracheotomy, whether preserving tracheal intubation after operation or not, and postoperative emergency tracheal intubation were included in the perioperative airway events of infantile subglottic hemangioma. The relevant influencing factors of perioperative airway events were analyzed so that meaningful statistical indicators were selected for grouped logistic regression analysis, and the correlation was evaluated based on value and 95% confidence interval(). Based on the correlation between influencing factors and airway events, perioperative airway management was discussed. ①The degree of tracheal stenosis was a risk factor for SpO₂ decline(95%[2.121-33.818]); ②The degree of airway stenosis, history of comorbid cardiovascular disease and respiratory disease were the influencing factors for intraoperative emergency tracheal intubation(95%[0.863-21.692], [0-+∞] and [1.741-232.403], respectively); ③The degree of airway stenosis was the influencing factor for postoperative emergency tracheal intubation(95%[1.277-20.421]); ④The degree of airway stenosis was a risk factor for whether preserving postoperative tracheal intubation or not(95%[1.523-13.296]). ①Infants with a history of preoperative underlying diseases are more likely to present with intraoperative airway instability and SpO₂ decline, which deserves more preoperative and postoperative attention. Tracheal intubation should be performed timely in case of intraoperative SpO₂ decline. ②Preoperative tracheotomy should be performed in infants with preoperative grade Ⅲ airway stenosis, especially those with comorbid heart diseases or respiratory diseases. ③The degree of airway stenosis is an extremely important influencing factor for perioperative airway management of infantile subglottic hemangioma. For infants whose airway stenosis were greater than 60% of airway diameter, the airway maintenance should be closely monitored. Once SpO₂ decreases, tracheal intubation should be performed immediately. It's recommended to preserve tracheal intubation so as to ensure the airway stability. The tracheal intubation could be prolonged to 48-72 hours postoperatively. ④The surgical approach has no significant effect on perioperative airway management.
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http://dx.doi.org/10.13201/j.issn.2096-7993.2021.06.004DOI Listing
June 2021

[Tumor necrosis factor α inhibits the migration of human oligodendrocyte precursor cells in vitro].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2021 Jul;37(7):585-589

The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510515; Laboratory of Pediatrics, The Sixth Medical Center of PLA General Hospital, Beijing 100048, China. *Corresponding author, E-mail:

Objective To investigate the impact of tumor necrosis factor alpha (TNF-α) on the migration ability of oligodendrocyte precursor cells (OPCs) derived from human adult neural stem cells (NSCs) for transplantation therapy. Methods Flow cytometry was performed to detect the expressions of platelet derived growth factor receptor alpha (PDGFRα) and ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1 (ST8SIA1/A2B5) in human OPCs. OPCs were cultured and incubated with 0, 10, 100, 200 ng/mL TNF-α for 18 hours. OPC viability was detected by CCK-8 assay and OPC migration was detected by Transwell migration assay. Results OPCs derived from human adult NSC specifically expressed PDGFRα (87.9%) and A2B5 (40.0%). Treatment with 10 ng/mL TNF-α had no impact on OPC viability while both 100 ng/mL and 200 ng/mL TNF-α treatments decreased OPC viability significantly. OPC migration was reduced significantly in 10 ng/mL TNF-α treated group compared with the blank control. Conclusion TNF-α inhibits the migration of the cultured OPCs.
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July 2021

High throughput proteomic and metabolic profiling identified target correction of metabolic abnormalities as a novel therapeutic approach in head and neck paraganglioma.

Transl Oncol 2021 Aug 9;14(8):101146. Epub 2021 Jun 9.

Department of Otolaryngology Head & Neck Surgery, The Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, No. 639, Zhi-Zao-Ju Road, Shanghai 200011, China; Ear Institute, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China. Electronic address:

Head and neck paragangliomas (HNPGLs) are rare neoplasms that represent difficult treatment paradigms in neurotology. Germline mutations in genes encoding succinate dehydrogenase (SDH) are the cause of nearly all familial HNPGLs. However, the molecular mechanisms underlying tumorigenesis remain unclear. Mutational analysis identified 6 out of 14 HNPGLs harboring clinicopathologic SDH gene mutations. The SDHB gene was most frequently mutated in these patients, and western blot showed loss of SDHB protein in tumors with SDHB mutations. The paraganglioma cell line (PGL-626) was established from a sample that harbored a missense SDHB mutation (c.649C > T). Spectrometric analysis using tandem mass tags identified 151 proteins significantly differentially expressed in HNPGLs compared with normal nerves. Bioinformatics analyses confirmed the high level of enrichment of oxidative phosphorylation and metabolism pathways in HNPGLs. The mitochondrial complex subunits NDUFA2, NDUFA10, and NDUFA4, showed the most significantly increased expression and were localized predominantly in the cytoplasm of PGL-626 cells. The mitochondrial complex I inhibitor metformin exerted dose-dependent inhibitory effects on PGL-626 cells via cooperative down-regulation of NDUFA2, 4, and 10, with a significant decrease in the levels of reactive oxygen species and mitochondrial membrane potential. Further metabolomic analysis of PGL-626 cells showed that metabolites involved in central carbon metabolism in cancer and sphingolipid signaling pathways, pantothenate and CoA biosynthesis, and tryptophan and carbon metabolism were significantly altered after metformin treatment. Thus, this study provides insights into the molecular mechanisms underlying HNPGL tumorigenesis and identifies target correction of metabolic abnormalities as a novel therapeutic approach for this disease.
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http://dx.doi.org/10.1016/j.tranon.2021.101146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193622PMC
August 2021

Thermal Safety of Endoscopic Usage in Robot-Assisted Middle Ear Surgery: An Experimental Study.

Front Surg 2021 14;8:659688. Epub 2021 May 14.

Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

The widespread application of endoscopic ear surgery (EES), performed through the external auditory canal, has revealed the limitations of the one-handed technique. The RobOtol® (Collin ORL, Bagneux, France) otological robotic system has been introduced to enable two-handed procedures; however, the thermal properties of dedicated endoscopes, which are usually used in neurosurgery, called "neuro-endoscopes," have not yet been clarified for the robotic systems. In this study, we aimed to profile the thermal characteristics of two dedicated neuro-endoscopes, as compared to endoscopes used routinely in manual EES, called "oto-endoscopes," and defined by a smaller diameter and shorter length, and to discuss the safe application of robotic assistance in EES. Two neuro-endoscopes (3.3 mm, 25 cm, 0°/30°) were studied using two routine light sources (LED/xenon), and two routine oto-endoscopes (3 mm, 14 cm, 0°/30°) were initially measured to provide a comprehensive comparison. Light intensities and temperatures were measured at different power settings. The thermal distributions were measured in an open environment and a human temporal bone model of EES. The cooling measures were also studied. Light intensity was correlated with stabilized tip temperatures ( < 0.01, = 0.8719). Under 100% xenon power, the stabilized temperatures at the tips of 0°, 30° neuro-endoscopes, and 0°, 30° oto-endoscopes were 96.1, 60.1, 67.8, and 56.4°C, respectively. With 100% LED power, the temperatures decreased by about 10°C, respectively. For the 0° neuro-endoscope, the illuminated area far away 1cm from the tip was below 37°C when using more than 50% both power, while this distance for 30° neuro-endoscope was 0.5 cm. In the EES temporal bone model, the round window area could reach 59.3°C with the 0° neuro-endoscope under 100% xenon power. Suction resulted in a ~1-2°C temperature drop, while a 10 mL saline rinse gave a baseline temperature which lasted for 2.5 min. Neuro-endoscope causes higher thermal releasing in the surgical cavity of ESS, which should be especially cautious in the robotic system usage. Applying submaximal light intensity, a LED source and intermittent rinsing should be considered for the safer robot-assisted EES using a neuro-endoscope that allows a two-handed surgical procedure.
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http://dx.doi.org/10.3389/fsurg.2021.659688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160440PMC
May 2021

Identifying the functions of two biomarkers in human oligodendrocyte progenitor cell development.

J Transl Med 2021 05 1;19(1):188. Epub 2021 May 1.

The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China.

Background: Human oligodendrocyte precursor cells (hOPCs) are an important source of myelinating cells for cell transplantation to treat demyelinating diseases. Myelin oligodendrocytes develop from migratory and proliferative hOPCs. It is well known that NG2 and A2B5 are important biological markers of hOPCs. However, the functional differences between the cell populations represented by these two biomarkers have not been well studied in depth.

Objective: To study the difference between NG2 and A2B5 cells in the development of human oligodendrocyte progenitor cells.

Methods: Using cell sorting technology, we obtained NG2+/-, A2B5+/- cells. Further research was then conducted via in vitro cell proliferation and migration assays, single-cell sequencing, mRNA sequencing, and cell transplantation into shiverer mice.

Results: The proportion of PDGFR-α + cells in the negative cell population was higher than that in the positive cell population. The migration ability of the NG2+/-, A2B5+/- cells was inversely proportional to their myelination ability. The migration, proliferation, and myelination capacities of the negative cell population were stronger than those of the positive cell population. The ability of cell migration and proliferation of the four groups of cells from high to low was: A2B5- > NG2- > NG2+ > A2B5+. The content of PDGFR-α+ cells and the ability of cell differentiation from high to low was: NG2- > A2B5- > A2B5+ > NG2+.

Conclusion: In summary, NG2+  and A2B5+ cells have poor myelination ability due to low levels of PDGFR-α+ cells. Therefore, hOPCs with a higher content of PDGFR-α+ cells may have a better effect in the cell transplantation treatment of demyelinating diseases.
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http://dx.doi.org/10.1186/s12967-021-02857-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088696PMC
May 2021

Study on the Safety of Human Oligodendrocyte Precursor Cell Transplantation in Young Animals and Its Efficacy on Myelination.

Stem Cells Dev 2021 Jun 29;30(11):587-600. Epub 2021 Apr 29.

The Second Clinical College, Southern Medical University, Guangzhou, China.

Oligodendrocyte precursor cells (OPCs) can differentiate into myelinating oligodendrocytes during embryonic development, thereby representing an important potential source for myelin repair or regeneration. To the best of our knowledge, there are very few OPCs from human sources (human-derived OPCs [hOPCs]). In this study, we aimed to evaluate the safety and remyelination capacity of hOPCs developed in our laboratory, transplanted into the lateral ventricles of young animals. Several acute and chronic toxicity experiments were conducted in which different doses of hOPCs were transplanted into the lateral ventricles of Sprague-Dawley rats of different ages. The toxicity, biodistribution, and tumor formation ability of the injected hOPCs were examined by evaluating the rats' vital signs, developmental indicators, neural reflexes, as well as by hematology, immunology, and pathology. In addition, the hOPCs were transplanted into the corpus callosum of the shiverer mouse to verify cell myelination efficacy. Overall, our results show that transplanted hOPCs into young mice are nontoxic to their organ function or immune system. The transplanted cells engrafted in the brain and did not appear in other organs, nor did they cause tissue proliferation or tumor formation. In terms of efficacy, the transplanted hOPCs were able to form myelin in the corpus callosum, alleviate the trembling phenotype of shiverer mice, and promote normal development. The transplantation of hOPCs is safe; they can effectively form myelin in the brain, thereby providing a theoretical basis for the future clinical transplantation of hOPCs.
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http://dx.doi.org/10.1089/scd.2021.0012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165470PMC
June 2021

Trajectory modeling of endothelial-to-mesenchymal transition reveals galectin-3 as a mediator in pulmonary fibrosis.

Cell Death Dis 2021 03 26;12(4):327. Epub 2021 Mar 26.

MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing, China.

The endothelial-to-mesenchymal transition (EndMT) is an important source of fibrotic cells in idiopathic pulmonary fibrosis (IPF). However, how endothelial cells (ECs) are activated and how EndMT impact IPF remain largely elusive. Here, we use unsupervised pseudotemporal analysis to recognize the heterogeneity of ECs and reconstruct EndMT trajectory of bleomycin (BLM)-treated Tie2;Rosa26 IPF mice. Genes like C3ar1 and Lgals3 (protein name galectin-3) are highly correlated with the transitional pseudotime, whose expression is gradually upregulated during the fate switch of ECs from quiescence to activation in fibrosis. Inhibition of galectin-3 via siRNA or protein antagonists in mice could alleviate the pathogenesis of IPF and the transition of ECs. With the stimulation of human pulmonary microvascular endothelial cells (HPMECs) by recombinant proteins and/or siRNAs for galectin-3 in vitro, β-catenin/GSK3β signaling and its upstream regulator AKT are perturbed, which indicates they mediate the EndMT progress. These results suggest that EndMT is essential to IPF process and provide potential therapeutic targets for vascular remodeling.
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http://dx.doi.org/10.1038/s41419-021-03603-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998015PMC
March 2021

Differences in Calcium Clearance at Inner Hair Cell Active Zones May Underlie the Difference in Susceptibility to Noise-Induced Cochlea Synaptopathy of C57BL/6J and CBA/CaJ Mice.

Front Cell Dev Biol 2020 5;8:635201. Epub 2021 Feb 5.

Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Noise exposure of a short period at a moderate level can produce permanent cochlear synaptopathy without seeing lasting changes in audiometric threshold. However, due to the species differences in inner hair cell (IHC) calcium current that we have recently discovered, the susceptibility to noise exposure may vary, thereby impact outcomes of noise exposure. In this study, we investigate the consequences of noise exposure in the two commonly used animal models in hearing research, CBA/CaJ (CBA) and C57BL/6J (B6) mice, focusing on the functional changes of cochlear IHCs. In the CBA mice, moderate noise exposure resulted in a typical fully recovered audiometric threshold but a reduced wave I amplitude of auditory brainstem responses. In contrast, both auditory brainstem response threshold and wave I amplitude fully recovered in B6 mice at 2 weeks after noise exposure. Confocal microscopy observations found that ribbon synapses of IHCs recovered in B6 mice but not in CBA mice. To further characterize the molecular mechanism underlying these different phenotypes in synaptopathy, we compared the ratio of Bax/Bcl-2 with the expression of cytochrome-C and found increased activity in CBA mice after noise exposure. Under whole-cell patch clamped IHCs, we acquired two-photon calcium imaging around the active zone to evaluate the Ca clearance rate and found that CBA mice have a slower calcium clearance rate. Our results indicated that excessive accumulation of calcium due to acoustic overexposure and slow clearance around the presynaptic ribbon might lead to disruption of calcium homeostasis, followed by mitochondrial dysfunction of IHCs that cause susceptibility of noise-induced cochlear synaptopathy in CBA mice.
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http://dx.doi.org/10.3389/fcell.2020.635201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902005PMC
February 2021

A microscope-assisted endoscopic transcanal transpromontorial approach for vestibular schwannoma resection: a preliminary report.

Eur Arch Otorhinolaryngol 2021 Feb 1. Epub 2021 Feb 1.

Department of Otolaryngology-Head and Neck Surgery, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China.

Objective: To evaluate the feasibility of a microscope-assisted endoscopic transcanal transpromontorial approach (METTA) for the removal of small vestibular schwannomas (VS) limited to the internal auditory canal (IAC), and introduce a modification without external auditory canal (EAC) closure.

Methods: Between August 2018 and February 2019, seven patients with intrameatal VS underwent surgery in our center, endoscopic transcanal transpromontorial approach was applied in the first 2 patients and the rest 5 patients were operated via METTA. Treatment outcomes including efficacy of tumor resection, facial nerve outcome, operation time and post-operative course were recorded and analyzed.

Results: All seven patients were pathologically confirmed to have intrameatal VS. Total tumor removal was achieved in all cases. Two patients experienced cerebrospinal fluid leakage which resolved spontaneously within 5 days. The average operation time was 161.41 ± 18.42 min. All patients presented normal facial nerve function 1 month after surgery.

Conclusion: The METTA was effective in the removal of intrameatal VS. It can be an alternative surgical option for intrameatal VS with no serviceable hearing.
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http://dx.doi.org/10.1007/s00405-021-06612-zDOI Listing
February 2021

Bimodal Stimulation in Children With Bilateral Profound Sensorineural Hearing Loss: A Suitable Intervention Model for Children at the Early Developmental Stage.

Otol Neurotol 2020 12;41(10):1357-1362

Department of Otolaryngology-Head and Neck Surgery, Ninth People's Hospital.

Objective: To evaluate the auditory and speech benefit of bimodal stimulation for prelingual deafened cochlear implantation recipients.

Study Design: Retrospective and comparative study.

Setting: Tertiary referral center.

Patients: Fifty-six children with bilateral prelingual profound sensorineural hearing loss were enrolled, including 28 consecutive children with unilateral cochlear implantation (CI group), and 28 consecutive children with bimodal stimulation (BI group) who used an additional hearing aid (HA) in the contralateral ear.

Main Outcome Measures: Hearing assessments included the Infant-Toddler Meaningful Auditory Integration Scale (IT-MAIS) and Categories of Auditory Performance (CAP). Speech evaluations included the Meaningful Use of Speech Scale (MUSS), and Speech Intelligibility Rating (SIR). These measurements were evaluated at the first mapping of cochlear implants and 0.5, 1, 3, 6, 12, 18, 24 months after. Data were analyzed by repeated measures analysis.

Results: The mean ages of BI and CI groups were similar (17.6 ± 6.87 vs 19.0 ± 8.10 months, p = 0.497). The initial scores for hearing and speech assessments showed no differences between the two groups, apart from IT-MAIS (2.46 ± 0.631 in BI group vs 0.50 ± 0.279 in CI group, p = 0.004). The auditory and speech development over time were different in the two groups as seen in IT-MAIS (p < 0.001), CAP (p = 0.029), MUSS (p < 0.001), and SIR (p < 0.001). A continuing but stable difference was observed in CAP, MUSS, and SIR at 3, 18, and 12 months after the first mapping, respectively. In addition, the BI group had better IT-MAIS scores at 3 and 6 months compared with the CI group; however, the difference was not significant after 12 months.

Conclusion: Bimodal stimulation is beneficial for prelingually deafened CI recipients who have minimal contralateral residual hearing when bilateral CIs are not available. Hearing aid use in the contralateral ear might be recommended for children after unilateral cochlear implantation to facilitate the development of auditory and speech skills.
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http://dx.doi.org/10.1097/MAO.0000000000002812DOI Listing
December 2020

[Distribution of juvenile laryngeal papilloma in different stages].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2020 Dec;34(12):1088-1092

Department of Otolaryngology Head and Neck Surgery,Shanghai Ninth People's Hospital,School of Medicine,Shanghai Jiao Tong University,Shanghai,200011,China.

To study the anatomical distribution and tumor extent of juvenile laryngeal papilloma(JLP), and to sum up the similarity and difference in distribution between initiatial and recurrent tumor. Data of 65 patients with JLP who were admitted to the Ear Institute, School of Medicine, Shanghai Jiao Tong University from January 2011 to December 2018 were retrospectively analyzed. The RRP tumor assessment method proposed by Derkay et al. was referred to, in which larynx was divided in to 11 anatomical sites. 2.9±1.3 Laryngeal anatomical sites were involved in patients with initial tumor, while that was 3.1±1.5 in patients with recurrent tumor. The most common sites were true vocal fords, anterior commissure and false vocal fords in both group; and the least ones were subglottis, posterior glottis and ary-epiglottic fold. However, subglottis(=0.038) and trachea(=0.007) were more likely to be involved in recurrent tumor, with statistical differences. There were differences in distribution of JLP between initial and recurrent tumor, which might be the result of suitable areas for HPV survival or micro-lesion of residual tumor.
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http://dx.doi.org/10.13201/j.issn.2096-7993.2020.12.008DOI Listing
December 2020

[A prospective comparative study on the short-term effect of endoscopic myringoplasty in dry and wet ears].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2020 Oct;34(10):874-878

Department of Otorhinolaryngology Head and Neck Surgery,Ninth People's Hospital,Shanghai Jiaotong University School of Medicine.

To investigate the success rate, dry ear time and hearing improvement of myringoplasty on chronic suppurative otitis media(CSOM) patients under dry and wet ear conditions. Patients with CSOM who underwent endoscopic type Ⅰ tympanoplasty between January 2018 and October 2019 in West China Hospital were prospectively enrolled. Before the operation, Ear HRCT, oto-endoscope and pure tone audiometry were completed. According to whether there was mucus and purulent secretion of middle ear accompanied with edema of tympanic mucosa, patients were divided into wet ear group(32 cases) and dry ear group(69 cases). All patients were followed up at half-month, 1 month and 3 months after surgery, with assessment of endoscopy and pure tone audiometry. SPSS 19.0 was used to compare the therapeutic effect of myringoplasty on different condition CSOM patients. Compared with wet ear group, a higher level of perforation healing rate was found in dry ear group, but there was no significant difference between them(97.1% vs. 90.6%, =0.367). The rate of dry ear was 98.6% and 93.7% in dry ear group and wet ear group respectively within three months after surgery, among which the rate of dry ear was 14.5%, 52.2% and 31.9% in dry ear group in half month, 1 month and 3 months after surgery, while that in wet ear group was 28.1%, 40.6% and 25.0% respectively. There was no significant difference in the time to dry ear after surgery between the two groups(=0.172). Meanwhile, changes of air bone gap(ABG) between pre-operation and 3 months after operation in dry and wet ear groups was similar [(9.87±1.08) dB vs. (12.74±1.77) dB, =0.154]. When included patients were analyzed as a whole, the ABG at 3 months was significantly lower than 1 month after operation(<0.01), similar result was also found when compared the ABG at 1 month after operation with pre-operation(<0.01). The air conduction threshold was improved from (42.09±1.74) dB HL before operation to (29.41±1.61) dB HL at 3 months after operation(<0.01), however, there was no significant change in bone conduction threshold(=0.338). There is no significant difference in the therapeutic effect of myringoplasty on CSOM patients under dry and wet ear conditions. Direct type Ⅰ tympanoplasty on wet ear patients has no adverse effect on the prognosis.
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http://dx.doi.org/10.13201/j.issn.2096-7993.2020.10.003DOI Listing
October 2020

Development of methods for detecting the fate of mesenchymal stem cells regulated by bone bioactive materials.

Bioact Mater 2021 Mar 19;6(3):613-626. Epub 2020 Sep 19.

State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, Tsinghua University, Beijing, 100084, People's Republic of China.

The fate of mesenchymal stem cells (MSCs) is regulated by biological, physical and chemical signals. Developments in biotechnology and materials science promoted the occurrence of bioactive materials which can provide physical and chemical signals for MSCs to regulate their fate. In order to design and synthesize materials that can precisely regulate the fate of MSCs, the relationship between the properties of materials and the fate of mesenchymal stem cells need to be clarified, in which the detection of the fate of mesenchymal stem cells plays an important role. In the past 30 years, a series of detection technologies have been developed to detect the fate of MSCs regulated by bioactive materials, among which high-throughput technology has shown great advantages due to its ability to detect large amounts of data at one time. In this review, the latest research progresses of detecting the fate of MSCs regulated by bone bioactive materials (BBMs) are systematically reviewed from traditional technology to high-throughput technology which is emphasized especially. Moreover, current problems and the future development direction of detection technologies of the MSCs fate regulated by BBMs are prospected. The aim of this review is to provide a detection technical framework for researchers to establish the relationship between the properties of BMMs and the fate of MSCs, so as to help researchers to design and synthesize BBMs better which can precisely regulate the fate of MSCs.
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http://dx.doi.org/10.1016/j.bioactmat.2020.08.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508719PMC
March 2021

Diagnostic value of dynamic contrast-enhanced magnetic resonance imaging in Bell's palsy.

Acta Radiol 2020 Sep 24:284185120958414. Epub 2020 Sep 24.

Department of Otorhinolaryngology, Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.

Background: Bell's palsy (BP) is the most common form of acute facial nerve disorder and is characterized by rapid onset peripheral facial palsy of unknown etiology.

Purpose: To explore the diagnostic value of dynamic contrast-enhanced (DCE) magnetic resonance imagine (MRI) in patients with BP particularly in involved segments.

Material And Methods: A retrospective analysis was performed on the patients with BP who underwent routine MRI examinations and volumetric interpolated breath-hold examination (VIBE) sequence-based DCE-MRI before surgery in our department from January 2015 to July 2020. DCE-MRI data postprocessing was performed on Siemens Workstation Extended MR Work Space 2.6.3.5. Statistical analyses were performed using SPSS®v.19.0. The inter-observer reliability was evaluated with kappa identity test and McNemar's test.

Results: Twenty-three patients were included. On conventional contrast-enhanced MRI, the two observers were inconsistent in their diagnosis of lesion segments of facial nerve (Kappa 0.426,  = 0.009). Compared to the results of the surgery, the diagnostic consistency of both observers was general (Kappa 0.476,  < 0.001 and Kappa 0.430,  < 0.001, respectively). The diagnostic results of DCE-MRI for lesion segments of the facial nerve were consistent between the two observers (Kappa 0.929,  < 0.001). Compared to the results of the surgery, the diagnostic consistency of both observers was good (Kappa 0.753,  < 0.001 and Kappa 0.731,  < 0.001, respectively).

Conclusion: Compared to conventional MRI, DCE-MRI has good stability and repeatability in the diagnosis of the lesion segments of the facial nerve as well as a good specificity and accuracy.
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http://dx.doi.org/10.1177/0284185120958414DOI Listing
September 2020

Proteomic screening identifies PML/p53 axis as a potential treatment target of facial nerve schwannomas.

Am J Transl Res 2020 15;12(8):4237-4250. Epub 2020 Aug 15.

Department of Otolaryngology Head & Neck Surgery, The Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine Shanghai, China.

Facial nerve schwannomas (FNS) represents one of the more difficult treatment paradigms in neurotology. The aim of this study is to investigate the molecular alterations of FNS, thus providing potential targets treatable in the tumour. We for the first time suggest that the deficiency of merlin (the product of tumour suppressor) is probably one of the key mechanisms underlying FNS tumourigenesis, although no disease-causing mutations were demonstrated in tumour samples. TMT-labeled spectrometry analysis was used to identify the proteome of FNS relative to nerve controls. Eighty-four significantly deregulated proteins were identified, among which the PML tumour suppressor showed the most significantly increased expression. The PML protein was distributed in the nucleoplasm of non-tumorous Schwann cells, whereas it was preferentially confined to the cytoplasm of FNS cultures. Overexpression of PML and p53, partner proteins positively regulating each other to trigger apoptosis, was further confirmed in FNS tissues/cultures, and this correlated with a significant decrease in the proliferation of FNS cultures in comparison to Schwann cells. It is therefore probable that PML-p53 overexpression may occur as part of protective cellular mechanisms in response to the proliferation signal mediated by loss of merlin in FNS, in accordance with the fact that the tumour is benign slow-growing. This hypothesis was supported by the finding that the p53 activator nutlin-3 could exert dose-dependent inhibitory effects on FNS cultures via a cooperative induction of PML-p53 levels. Thus, the current study may present a potential treatment target directed on the molecular mechanisms of this disease.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476122PMC
August 2020

[Optimization of cryopreservative method for human fetal brain neural stem cells-derived oligodendrocyte precursor cells].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2020 Mar;36(3):248-254

Laboratory of Pediatrics, Sixth Medical Center, PLA General Hospital, Beijing 100048, China. *Corresponding author, E-mail:

Objective To explore the impact of various conditions during cryopreservation on the survival rate of oligodendrocyte precursor cells (OPCs) derived from human fetal neural stem cells. Methods We compared the cell viability of oligodendrocyte precursors harvested with or without digestion. Then we tested the impact of 3 factors during cryopreservation, freezing solutions (solution with 70 mL/L DMSO and 930 mL/L FBS; solution with 70 mL/L DMSO, 300 mL/L FBS and OPC culture medium; solution with 70 mL/L DMSO, 300 mL/L FBS, 0.2 mol/mL trehalose and OPC culture medium; solution with 70 mL/L DMSO, 300 mL/L FBS, 300 mL/L HES and OPC culture medium), freezing methods (the step-wised freezing or rapid freezing within liquid nitrogen) and storage durations for the better survival rate of OPCs. The optimized method with the best survival rate of OPCs was implemented and at day 7 after recovery, the viability, OPCs specific markers [platelet derived growth factor receptor alpha (PDGFRα), ST8 alpha-N-acetyl-neuraminide alpha-2, 8-sialyltransferase 1 (ST8SIA1/A2B5), chondroitin sulfate proteoglycan 4 (CSPG4/NG2), ki67 were tested and compared with immunofluorescent cytochemical staining. Results Harvesting with digestion contributed to higher OPCs survival rate. OPCs of rapid freezing had survival rates less than 30% and couldn't be re-cultured. The step-wised freezing group showed higher recovery rate. Harvesting with digestion, preservation solution with trehalose, using 2.0×10/mL of cell number, step-wised freezing, contributed to the highest OPCs survival rate reaching (75.73±6.66)%. Compared with the fresh cultured group, cell proliferation, ki67 antigen, PDGFRα, A2B5 and NG2 expression of OPCs were similar in the recovered cells. Storage duration didn't affect OPCs survival rate. Conclusion Harvesting with digestion, step-wised freezing, preservation solution with trehalose contribute to higher OPCs survival rate during cryopreservation and cell-thawing. Storage time doesn't affect phenotypes and viability of OPCs.
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March 2020

Quick stabilization of capillary for rapid determination of potassium ions in the blood of epilepsy patients by capillary electrophoresis without sample pretreatment.

Electrophoresis 2020 08 18;41(15):1273-1279. Epub 2020 May 18.

College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, P. R. China.

Mutations in the potassium channel genes may be linked to the development of epilepsy and affect the blood potassium levels. Therefore, accurate determination of potassium in the blood will be critical to diagnose the cause of epilepsy. CE is a competent technique for the fast detection of multiple ions, but complicated matrices of a blood sample may cause significant variation of migration times and the peak shape. In this work, a procedure for rapid stabilization of the capillary inner surface through preflushing of a blood sample was employed. The process takes only 40 min for a capillary and then it can be used for more than 2 weeks. No pretreatment of the blood sample or other surface modification of the capillary is needed for the analysis. The RSDs of the migration time and peak area were reduced to 1.5 and 5.1% from 12.6 and 14.5%, respectively. The proposed method has been successfully applied to the determination of the potassium contents in the blood sample of patients with epilepsy at different stages. The recoveries of potassium ions in these blood samples are in a range from 86.5 to 104.5%.
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http://dx.doi.org/10.1002/elps.202000022DOI Listing
August 2020

Competitive adsorption of tylosin, sulfamethoxazole and Cu(II) on nano-hydroxyapatitemodified biochar in water.

Chemosphere 2020 Feb 16;240:124884. Epub 2019 Sep 16.

School of Environment, Tsinghua University, Beijing, 100084, China. Electronic address:

Antibiotics and heavy metals are frequently detected simultaneously in water environment. In this study, the competitive adsorption behavior of tylosin (TYL) and sulfamethoxazole (SMX) on nano-hydroxyapatite modified biochar ([email protected]) in accordance with Cu(II) in single, binary and ternary systems was investigated. The specific surface area of [email protected] was 566.056 m/g. The adsorption of TYL on [email protected] reduced by 13.36%-41.04% or 9.92%-38.69% with Cu(II) and SMX in the solution, respectively. The suppression of SMX was stronger than Cu(II) on the adsorption of TYL when the SMX or Cu(II) was constant. The adsorption of SMX increased by 2.01-3.56 times in the present of Cu(II), while suppressed by TYL up to 42.30%. Due to the bridging of TYL or SMX between the [email protected] and Cu(II) and destroying of bound water surrounded, the adsorption of Cu(II) increased to a greater extent. Electrostatic interaction and H-bond were the two main interactions between TYL, SMX and Cu(II) and [email protected] π-π interactions was also interaction between the SMX and [email protected]
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http://dx.doi.org/10.1016/j.chemosphere.2019.124884DOI Listing
February 2020

MiR-486-5p inhibits IL-22-induced epithelial-mesenchymal transition of breast cancer cell by repressing Dock1.

J Cancer 2019 19;10(19):4695-4706. Epub 2019 Aug 19.

College of Nursing, Weifang Medical University, Weifang, China.

Epithelial-mesenchymal transition (EMT) is one of important steps that lead to cancer metastasis. Interleukin-22 (IL-22) is a T helper 17 (Th17) cells-secreted cytokine, it can promote invasion and metastasis of many cancers. MiR-486-5p is a microRNA that known to function as a tumor suppressor, and bioinformatics analysis predicts that Dock-1 has a binding site of miR-486-5p. In current research, we examined the relative expression levels of miR-486-5p and Dock-1 in 80 pairs of breast cancer tissues and corresponding adjacent normal tissues, also the effects of modifying their levels in cultured cells. We illustrated that IL-22 and Dock1 promote the invasion, metastasis, and EMT of breast cancer using Transwell invasion assay, western blot and immunofluorescence. MiR-486-5p directly bound the Dock1 mRNA 3' untranslated region and inhibited IL-22-induced EMT of breast cancer cells via the Dock1/NF-κB/Snail signaling pathway. Dock1 overexpression reversed the effect caused by the overexpression of miR-486-5p. Overexpression of miR-486-5p or downregulation of Dock1 reduced pulmonary metastasis in mice. This study provided insight into a potential mechanism where miRNAs regulate breast cancer metastasis and provided a novel therapeutic target for breast cancer treatment.
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http://dx.doi.org/10.7150/jca.30596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6746125PMC
August 2019

Identification of a novel CDH23 gene variant associated with non-syndromic progressive hearing loss in a Chinese family: Individualized hearing rehabilitation guided by genetic diagnosis.

Int J Pediatr Otorhinolaryngol 2019 12 19;127:109649. Epub 2019 Aug 19.

Department of Otolaryngology-Head and Neck Surgery, 9th People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China. Electronic address:

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http://dx.doi.org/10.1016/j.ijporl.2019.109649DOI Listing
December 2019

Prognostic Factors of Long-Term Hearing Preservation in Small and Medium-Sized Vestibular Schwannomas After Microsurgery.

Otol Neurotol 2019 08;40(7):957-964

Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Ninth People's Hospital.

Objective: The authors evaluated the long-term hearing outcomes of patients with vestibular schwannoma (VS) to explore appropriate surgical treatment.

Study Design: Retrospective study.

Setting: Tertiary referral center.

Patients: A total of 138 patients diagnosed with small and medium-sized VS with serviceable hearing from January 2006 to December 2015.

Interventions: All patients underwent microsurgery via retrosigmoid (RSA) or middle cranial fossa approach (MFA) and were followed up for over 2 years.

Main Outcome Measures: Pre- and postoperative hearing, including pure tone audiometry, speech discrimination score, and auditory brainstem response (ABR), were analyzed.

Results: The mean tumor size and volume were 16.6 ± 3.4 mm and 1711.8 ± 918.5 mm, respectively. Preoperative hearing levels were Class A in 42, Class B in 67, and Class C in 29 patients. Patients with a tumor from the superior vestibular nerve (SVN) had better hearing at diagnosis. Postoperative hearing levels were Class A, B, C, and D for 28, 17, 32, and 61 patients. Hearing outcomes were significantly better in patients with normal intraoperative I wave on ABR. Hearing loss within 6 months had a positive effect on postoperative hearing. Better preoperative hearing and tumors from SVN were correlated with better postoperative hearing outcomes. Tumor size, cystic variation, or extension to the fundus of internal auditory canal had no influence on hearing preservation.

Conclusions: Better preoperative hearing, shorter hearing loss period, tumors from SVN, and normal intraoperative I wave are prognostic factors for serviceable hearing. RSA and MFA are effective and safe for tumor removal and hearing preservation.
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http://dx.doi.org/10.1097/MAO.0000000000002284DOI Listing
August 2019

Age-dependent copy number variations of TP53 tumour suppressor gene associated with altered phosphorylation status of p53 protein in sporadic schwannomas.

J Neurooncol 2019 Jul 2;143(3):369-379. Epub 2019 May 2.

Department of Otolaryngology Head & Neck Surgery, The Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, No. 639, Zhi-Zao-Ju Road, Shanghai, 200011, China.

Purpose: Point mutations of TP53 tumour suppressor are very rare in schwannomas. We aim to characterize the frequency of exonic copy-number changes of the gene in the tumour and to examine the association between TP53 alterations, phosphorylation status of p53 protein and clinical phenotypes.

Methods: The alterations of TP53 were screened by a combination of Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA) in a total of 44 vestibular schwannomas. The mutation index (MI) in a tumour was defined as the number of exons mutated/ the number of exons tested. Phosphorylation status of p53 protein was investigated by immunoblotting and immunofluorescence.

Results: MLPA analysis showed single and multi-exon deletion mutations of TP53 in 65.7% of the cases. Comparisons of clinical features between mutated and non-mutated patients established an association of TP53 mutations with progressive phenotypes, including an earlier formation and a larger tumour. In addition, there were significant correlations between MI and both patients' age and tumour size. The Ser 392 phosphorylation level of p53 varied among tumours, and correlation analysis revealed an age-dependent phosphorylation pattern. The majority of tumours with hyperphosphorylated p53 were from mutated and young patients, suggesting an association of Ser392 phosphorylation with the mutational status of TP53 involved in the acceleration of tumour growth in young individuals. Moreover, Ser 392 phosphorylation contributed to a nuclear accumulation of p53 in schwannona cultures with TP53 mutation.

Conclusions: An interplay between the mutation status of TP53, phosphorylation patterns and tumour behaviors might be established in the disease.
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http://dx.doi.org/10.1007/s11060-019-03176-1DOI Listing
July 2019

Gene expression profiles between cystic and solid vestibular schwannoma indicate susceptible molecules and pathways in the cystic formation of vestibular schwannoma.

Funct Integr Genomics 2019 Jul 5;19(4):673-684. Epub 2019 Apr 5.

Department of Otorhinolaryngology, Head & Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Previous research has shown that although NF2 gene mutation is the major cause of vestibular schwannoma (VS), it may not directly participate in cystic VS (CVS). To elucidate the underlying potential genetic mechanisms in the cystic formation of VS, we compared differences in gene expression between solid VS (SVS) and CVS via a bioinformatics analysis. The cDNA microarray method and miRNA sequencing were performed on 29 representative VSs (17 CVSs and 12 SVSs). A differential expression analysis was used to identify differentially expressed mRNAs (DEmRNAs) and miRNAs (DEmiRNAs). Then, miRNA-mRNA regulatory networks were constructed. Gene ontology (GO), a KEGG pathway enrichment analysis, and the protein-protein interaction (PPI) were used to analyze the co-differentially expressed DEmRNAs at the functional level. From the differential expression analyses, 1304 DEmRNAs, 55 DEmiRNAs, and hub genes including PTEN, FOXO1, FOXO3, VEGFA, and SIRT1 were identified. Histological evidence is presented to confirm the makeup of the hubs, which corresponded with the cDNA microarray. Our analysis revealed that the maps of apoptosis, cellular response to hypoxia, and the PI3K-Akt, AMPK, FOXO, and chemokine signaling pathways were significantly enriched. In addition, the TUNEL assay, immunoblotting analysis, and transmission electron microscope revealed increased degenerative changes in CVS. These findings could be the foundation for understanding the potential role of differential genes in the cystic formation of VS and be helpful in exploring the potential biomarkers for the differential diagnosis, prognosis, and development of drug targets for CVS.
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http://dx.doi.org/10.1007/s10142-019-00672-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6570702PMC
July 2019

[Transplantation of adipose-derived mesenchymal stem cell improves cardiac function in rats with acute myocardial infarction].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2019 Jan;35(1):31-38

Department of Pediatrics, Sixth Medical Center, PLA General Hospital, Beijing 100048, China. *Corresponding author, E-mail:

Objective To investigate the effects of the transplantation of autologous and allogeneic adipose-derived mesenchymal stem cells (ADMSCs) on the cardiac function in rats with acute myocardial infarction (AMI). Methods Firstly, ADMSCs were isolated from BN and Lewis rats, and the third generation were labeled with CM-DiI. Then 45 male Lewis rats were randomly divided into 3 groups (control group, autologous cell transplantation group, and allogeneic cell transplantation group). The AMI model was established by ligating the rats' left anterior descending artery, and then the infarcted myocardium as well as the peripheral parts was injected by the labeled ADMSCs via the endocardium. At 7 days after ADMSC transplantation, the infiltration of CD4 T lymphocytes, CD8 T lymphocytes and CD68 macrophages were detected by immunofluorescence technique. At 7, 14 and 28 days after transplantation, survival rate of the transplanted cells was compared. Then echocardiography was used to detect the rats' cardiac function at 28 days after transplantation. And the expression of α-smooth muscle actin (α-SMA) was detected by immunofluorescence technique for determining the angiogenesis near the transplanted cells. Results The positive rate of the cells labeled with CM-DiI was nearly 100%. At 7 days after transplantation, lymphocyte infiltration and macrophages were observed around the transplanted cells in the allogeneic cell transplantation group. No lymphocyte infiltration and macrophages were observed in the autologous cell transplantation group. Compared with allogeneic cell transplantation, the survival rate of the transplanted cells increased significantly. Moreover, the left ventricular short axis shortening rate (LVFS) and the diastolic left ventricular anterior wall thickness (LVAWTd) increased at 7, 14 and 28 days after transplantation. Meanwhile, the number of angiogenesis around the infarcted myocardium also significantly increased. Conclusion Autologous ADMSC transplantation is significantly better at improving cardiac function in AMI rats than allogeneic ADMSC transplantation.
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January 2019

Predictors of round window membrane visibility in pediatric cochlear implant surgery using temporal bone HRCT: A retrospective study.

Int J Pediatr Otorhinolaryngol 2019 Jun 16;121:150-153. Epub 2019 Mar 16.

Department of Otolaryngology, Head & Neck Surgery, Shanghai Ninth People's Hospital, Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases (14DZ2260300), Shanghai, China. Electronic address:

Objective: To predict round window membrane (RWM) visibility and electrode insertion sites using high-resolution computed tomography (HRCT) in pediatric cochlear implant surgery.

Materials And Methods: Sixty-two ears of 36 infants less than 1 year old were included in our study. Intraoperative RWM visibility was classified into three types corresponding to three different surgical approaches. Radiologic parameters were measured on preoperative axial temporal HRCT images and correlated with RWM visibility and surgical approaches.

Results: A significant correlation was found between the degree of RWM visibility and the following two parameters: 1) a line (l) was drawn from the posterior margin of the RWM to the intersection point of the posterior wall of the external auditory canal (EAC) and mastoid cortex. Another line (l) was drawn between the posterior margin of the RWM and the lateral margin of the FN. The angle between l and l was measured as angle A, P < 0.01, R = -0.809; 2) a line (l) was drawn from the anterior to posterior margin of the RWM, and the angle between l and l was measured as angle B, P < 0.01, R = -0.850. A nonsignificant correlation was found between the degree of RWM visibility and the facial recess width, p > 0.05, R = -0.00015.

Conclusion: RWM visibility showed a high correlation with the two angular measurements (angle A and angle B) and was associated with electrode insertion sites. In children less than one year old, surgeons can depend on those two parameters in predicting the RWM visibility.
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http://dx.doi.org/10.1016/j.ijporl.2019.03.017DOI Listing
June 2019

Long non-coding RNA ZEB2-AS1 promotes the proliferation, metastasis and epithelial mesenchymal transition in triple-negative breast cancer by epigenetically activating ZEB2.

J Cell Mol Med 2019 05 1;23(5):3271-3279. Epub 2019 Mar 1.

College of Nursing, Weifang Medical University, Weifang, China.

The triple-negative breast cancer is the most malignant type of breast cancer. Its pathogenesis and prognosis remain poor despite the significant advances in breast cancer diagnosis and therapy. Meanwhile, long noncoding RNAs (LncRNAs) play a pivotal role in the progression of malignant tumors. In this study, we found that LncRNA-ZEB2-AS1 was dramatically up-regulated in our breast cancer specimens and cells (MDA231), especially in metastatic tumor specimens and highly invasive cells, and high lncRNA-ZEB2-AS1 expression is associated with clinicopathologic features and short survival of breast cancer patients. LncRNA-ZEB2-AS1 promotes the proliferation and metastasis of MDA231 cells in SCID mice. Thus, it is regarded as an oncogene in triple-negative breast cancer. It is mainly endo-nuclear and situated near ZEB2, positively regulating ZEB2 expression and activating the epithelial mesenchymal transition via the PI3K/Akt/GSK3β/Zeb2 signaling pathway. Meanwhile, EGF-induced F-actin polymerization in MDA231 cells can be suppressed by reducing lncRNA-ZEB2-AS1 expression. The migration and invasion of triple-negative breast cancer can be altered through cytoskeleton rearrangement. In summary, we demonstrated that lncRNA-ZEB2-AS1 is an important factor affecting the development of triple-negative breast cancer and thus a potential oncogene target.
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http://dx.doi.org/10.1111/jcmm.14213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6484319PMC
May 2019

Dialysed caramel as an effective fluorophore for the simultaneous detection of three nitrophenols.

Talanta 2019 May 3;197:159-167. Epub 2019 Jan 3.

State Key Laboratory of Applied Organic Chemistry, Key Laboratory of Nonferrous Metals Chemistry and Resources Utilization of Gansu Province, Department of Chemistry, Lanzhou University, Lanzhou, Gansu 730000, China. Electronic address:

Low-cost and nontoxic fluorescent reagents are important for on-site analysis performed by non-professionals. In this work, a cheap and widely available food additive, caramel was used as an effective fluorescence reagent for the sensitive detection of 2,4,6-trinitrophenol (TNP), 2,4-dinitrophenol (DNP) and 4-nitrophenol (4-NP). Through a simple dialysis, fluorescent components of a commercial caramel were harvested with a yield as high as 60%. The structural characterization demonstrated that the fluorescent components were dehydrated oligomers of carbohydrates. Their fluorescence can be quenched by these nitrophenols. The quenching mechanism was speculated as inner filter effect. At pH 8, a linear range of 0.2-22 μM and a detection limit of 90 nM could be achieved for TNP. Based on the difference of their quenching efficiency at different pHs, TNP, DNP and 4-NP can be simultaneously determined by solving the linear equations obtained at pH 3, 5 and 8. Successful detection of these nitrophenols in the water and soil samples was performed with relative standard deviations of 1.1-5.9% and recoveries of 95-108% of spiked standards.
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http://dx.doi.org/10.1016/j.talanta.2019.01.006DOI Listing
May 2019

BoneBridge implantation in patients with single-sided deafness resulting from vestibular schwannoma resection: objective and subjective benefit evaluations.

Acta Otolaryngol 2018 Oct;138(10):877-885

a Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University , Shanghai , China.

Background: The BoneBridge could rehabilitate hearing for patients with single-sided deafness (SSD).

Objectives: To evaluate the objective and subjective benefits of BoneBridge implantation in patients after vestibular Schwannoma resection and to explore the factors affecting the benefits.

Material And Methods: We prospectively enrolled all 15 patients implanted with BoneBridge after VS resection from January to June 2017. The primary outcome was the ability to hear in noisy conditions. The secondary outcomes were the soft-band BoneBridge try-on rate, the frequency of BB use, the sound source localization test result, and questionnaire measures of quality of life (QoL).

Results: Patients showed better speech recognition ability in the presence of noise with the BoneBridge. The BoneBridge provided no help in sound localization, although most patients reported subjective sound localization benefits. The results of QoL questionnaires showed significant satisfaction with BoneBridge implantation. The unilateral hearing deprivation duration and high education levels had significant impacts on the subjective benefits of patients.

Conclusions: The BoneBridge could improve speech recognition performance in complex auditory backgrounds, as well as QoL, especially in patients with short unilateral hearing deprivation durations and high education levels.

Significance: The BoneBridge is an effective hearing aid for single-sided deafness patients after VS removal.
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http://dx.doi.org/10.1080/00016489.2018.1469789DOI Listing
October 2018

Immunological effects of the intraparenchymal administration of allogeneic and autologous adipose-derived mesenchymal stem cells after the acute phase of middle cerebral artery occlusion in rats.

J Transl Med 2018 12 5;16(1):339. Epub 2018 Dec 5.

Department of Pediatrics, Navy General Hospital, No. 6, Fucheng Road, Haidian District, Beijing, 100048, China.

Background: Adipose-derived mesenchymal stem cell (ADMSC) therapy can promote recovery from cerebral ischemia; however, more information regarding appropriate sources of ADMSCs is required. This study was aimed at analyzing the immunogenicity of rat ADMSCs by comparing the immunological effects of intraparenchymal administration of allogeneic ADMSCs (allo-ADMSCs) and autologous ADMSCs (auto-ADMSCs) after the acute phase of middle cerebral artery occlusion (MCAO) in rats.

Methods: Allo- or auto-ADMSCs from rats (1 × 10 cells) were transplanted into Lewis rats 8 days post MCAO. The immunogenicity of ADMSCs was analyzed using coculture with T lymphocytes. The in vivo immune response induced by rat ADMSCs and the viability, migration, and differentiation of transplanted ADMSCs were detected using immunohistochemistry. Apoptosis within the populations of transplanted cells were detected using a TUNEL assay. Infarct volume was detected by 2,3,5-triphenyltetrazolium chloride staining. Post-treatment neurological function was evaluated using a modified neurological severity score and rotarod test. Data were analyzed using Kruskal-Wallis and Mann-Whitney U tests.

Results: Compared with allo-ADMSCs, auto-ADMSCs showed lower immunogenicity and evoked weaker immunological responses. Allo-ADMSCs evoked significantly stronger protein expression of interleukin-2 and interferon-gamma, as well as the local accumulation of CD4+ T lymphocytes, CD8+ T lymphocytes, and microglial cells. This indicates that auto-ADMSCs may contribute to higher survival rates, longer survival time, wider migratory scope, and fewer apoptotic cells. In addition, a small number of transplanted auto-ADMSCs expressed astrocyte-like and neuron-like markers 28 days after transplantation. We did not observe surviving transplanted allo-ADMSCs at this time point. We also found that auto-ADMSCs induced a greater degree of functional recovery and a greater reduction in infarct volume than allo-ADMSCs 28 days after transplantation.

Conclusions: Auto-ADMSCs were more effective than allo-ADMSCs in promoting recovery and reducing the infarct volume of MCAO rats. This could be associated with better viability, migratory ability, and differentiation potential, as well as a lower rate of apoptosis. Confirmation of the superiority of auto-ADMSCs and clarification of the underlying mechanisms will provide a theoretical basis for the improved clinical treatment of cerebral infarction.
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http://dx.doi.org/10.1186/s12967-018-1709-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6280522PMC
December 2018

Synergistic effect of Nutlin-3 combined with MG-132 on schwannoma cells through restoration of merlin and p53 tumour suppressors.

EBioMedicine 2018 Oct 28;36:252-265. Epub 2018 Sep 28.

Department of Otolaryngology Head & Neck Surgery, The Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Ear Institute, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China. Electronic address:

Background: The great majority of sporadic vestibular schwannomas (VSs) are due to the mutations of the NF2 gene encoding merlin. Sporadic VSs exhibit variable growth patterns and only a small fraction of the tumours are fast-growing; however, the underlying mechanisms remain undefined.

Methods: DNA sequencing and dosage analysis were used to identify the NF2 mutation status in sporadic schwannomas. The expression and sub-cellular localization of merlin and p53-MDM2 were assessed by immunoblotting, qRT-PCR and immunofluorescence. In vitro and in vivo studies were performed to reveal the effects of Nutlin-3 (a MDM2 inhibitor) and/or MG-132(a proteasome inhibitor) on schwannomas. The proliferation of schwannoma cells was assessed by CCK-8 assay, EdU staining and Flow cytometry analysis.

Findings: Double genetic hits of NF2 tended to occur in fast-growing tumours, characterized by the absence of merlin. The deregulation of p53-MDM2 was demonstrated to mediate merlin-deficient tumour growth, characterized by a nuclear accumulation of stabilized MDM2, contributing to a nuclear export of p53 for degradation. Nutlin-3 blocked the proliferation of schwannoma cells via a cooperative recovery of merlin and p53, accompanied by the shuttling of both proteins from the cytoplasm to the nucleus. We further demonstrated a difference in the sensitivity to Nutlin-3 between schwannoma cells with and without merlin expression. Nutlin-3 combined with MG-132 narrowed this between-group difference and triggered stronger inhibitory effects on the growth of schwannomas through coordinated reactivation of p53.

Interpretation: These findings present treatment strategies directed on the pathogenesis of sporadic schwannomas. FUND: National Natural Science Foundation of China.
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http://dx.doi.org/10.1016/j.ebiom.2018.09.042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6197711PMC
October 2018
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