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      • KCI등재

        Genomic Correlates of Unfavorable Outcome in Locally Advanced Cervical Cancer Treated with Neoadjuvant Chemoradiation

        Yuchun Wei,Chuqing Wei,Liang Chen,Ning Liu,Qiuxiang Ou,Jiani C. Yin,Jiaohui Pang,Zhenhao Fang,Xue Wu,Xiaonan Wang,Dianbin Mu,Yang Shao,Jinming Yu,Shuanghu Yuan 대한암학회 2022 Cancer Research and Treatment Vol.54 No.4

        Purpose Neoadjuvant therapy modality can increase the operability rate and mitigate pathological risks in locally advanced cervical cancer, but treatment response varies widely. It remains unclear whether genetic alterations correlate with the response to neoadjuvant therapy and disease-free survival (DFS) in locally advanced cervical cancer. Materials and Methods A total of 62 locally advanced cervical cancer (stage IB-IIA) patients who received neoadjuvant chemoradiation plus radical hysterectomy were retrospectively analyzed. Patients’ tumor biopsy samples were comprehensively profiled using targeted next generation sequencing. Pathologic response to neoadjuvant treatment and DFS were evaluated against the association with genomic traits. Results Genetic alterations of PIK3CA were most frequent (37%), comparable to that of Caucasian populations from The Cancer Genome Atlas. The mutation frequency of genes including TERT, POLD1, NOS2, and FGFR3 was significantly higher in Chinese patients whereas RPTOR, EGFR, and TP53 were underrepresented in comparison to Caucasians. Germline mutations were identified in 21% (13/62) of the cohort and more than half (57%) had mutations in DNA damage repair genes, including BRCA1/2, TP53 and PALB2. Importantly, high tumor mutation burden, TP53 polymorphism (rs1042522), and KEAP1 mutations were found to be associated with poor pathologic response to neoadjuvant chemoradiation treatment. KEAP1 mutations, PIK3CA-SOX2 co-amplification, TERC copy number gain, and TYMS polymorphism correlated with an increased risk of disease relapse. Conclusion We report the genomic profile of locally advanced cervical cancer patients and the distinction between Asian and Caucasian cohorts. Our findings highlight genomic traits associated with unfavorable neoadjuvant chemoradiation response and a higher risk of early disease recurrence. PurposeNeoadjuvant therapy modality can increase the operability rate and mitigate pathological risks in locally advanced cervical cancer, but treatment response varies widely. It remains unclear whether genetic alterations correlate with the response to neoadjuvant therapy and disease-free survival (DFS) in locally advanced cervical cancer.Materials and MethodsA total of 62 locally advanced cervical cancer (stage IB-IIA) patients who received neoadjuvant chemoradiation plus radical hysterectomy were retrospectively analyzed. Patients’ tumor biopsy samples were comprehensively profiled using targeted next generation sequencing. Pathologic response to neoadjuvant treatment and DFS were evaluated against the association with genomic traits.ResultsGenetic alterations of <i>PIK3CA</i> were most frequent (37%), comparable to that of Caucasian populations from The Cancer Genome Atlas. The mutation frequency of genes including <i>TERT, POLD1, NOS2</i>, and <i>FGFR3</i> was significantly higher in Chinese patients whereas <i>RPTOR, EGFR</i>, and <i>TP53</i> were underrepresented in comparison to Caucasians. Germline mutations were identified in 21% (13/62) of the cohort and more than half (57%) had mutations in DNA damage repair genes, including <i>BRCA1/2, TP53</i> and <i>PALB2</i>. Importantly, high tumor mutation burden, <i>TP53</i> polymorphism (rs1042522), and <i>KEAP1</i> mutations were found to be associated with poor pathologic response to neoadjuvant chemoradiation treatment. <i>KEAP1</i> mutations, <i>PIK3CA-SOX2</i> co-amplification, <i>TERC</i> copy number gain, and <i>TYMS</i> polymorphism correlated with an increased risk of disease relapse.ConclusionWe report the genomic profile of locally advanced cervical cancer patients and the distinction between Asian and Caucasian cohorts. Our findings highlight genomic traits associated with unfavorable neoadjuvant chemoradiation response and a higher risk of early disease recurrence.

      • Model Predictive Control with Extrapolation Strategy for the Arm Current Commutation Control of Modular Multilevel Converter Operating in Quasi Two-Level Mode

        Xiaonan Gao,Wei Tian,Zhenbin Zhang,Ralph Kennel 전력전자학회 2019 ICPE(ISPE)논문집 Vol.2019 No.5

        Modular multilevel converters (MMCs) have become an attractive topology for medium-voltage motor drive applications due to their modular construction and voltage scalability. The main drawback of using MMC to drive motors is the large voltage variation of submodule (SM) capacitors when the motor is running at a low speed with a large load torque condition. Operating in the quasi two-level mode of MMCs is an effective solution for such a problem. The arm current commutation control is the most important part for the operation of MMCs in the quasi two-level mode. This paper proposes a new current commutation method. The general idea is to use the delay control method to realize the arm current commutation. Therefore, the key point is to decide when to delay the operation of a submodule at each step during the commutation process. In this paper, the model predictive control (MPC) method with extrapolation technique has been used to determine whether to delay the SM at the present moment. Therefore, the waveforms of the two arms in the same phase may not be completely complementary throughout the whole commutation period. Due to such non-complementary PWMs, the currents between two arms can be exchanged.

      • KCI등재

        Nucleocapsid Amino Acids 211 to 254, in Particular, Tetrad Glutamines, are Essential for the Interaction Between the Nucleocapsid and Membrane Proteins of SARS-Associated Coronavirus

        Xiaonan Fang,Lin-Bai Ye,Yijuan Zhang,Baozong Li,Shanshan Li,Lingbao Kong,Yuhua Wang,Hong Zheng,Wei Wang,Zhenghui Wu 한국미생물학회 2006 The journal of microbiology Vol.44 No.5

        GST pull-down assays were used to characterize the SARS-CoV membrane (M) and nucleocapsid (N)interaction, and it was found that the amino acids 211-254 of N protein were essential for this interaction. When tetrad glutamines (Q) were replaced with glutamic acids (E) at positions of 240-243 of the N protein, the interaction was disrupted.

      • SCIESCOPUSKCI등재

        Nucleocapsid Amino Acids 211 to 254, in Particular, Tetrad Glutamines, are Essential for the Interaction Between the Nucleocapsid and Membrane Proteins of SARS-Associated Coronavirus

        Fang, Xiaonan,Ye, Lin-Bai,Zhang, Yijuan,Li, Baozong,Li, Shanshan,Kong, Lingbao,Wang, Yuhua,Zheng, Hong,Wang, Wei,Wu, Zhenghui The Microbiological Society of Korea 2006 The journal of microbiology Vol.44 No.5

        GST pull-down assays were used to characterize the SARS-CoV membrane (M) and nucleocapsid (N) interaction, and it was found that the amino acids 211-254 of N protein were essential for this interaction. When tetrad glutamines (Q) were replaced with glutamic acids (E) at positions of 240-243 of the N protein, the interaction was disrupted.

      • KCI등재

        Glycyrrhetic acid monoglucuronide: sweetness concentration–response and molecular mechanism as a naturally high-potency sweetener

        Yongan Yang,Yuangang Wei,Xiaonan Guo,Pengfei Qi,Hailiang Zhu,Wenjian Tang 한국식품과학회 2019 Food Science and Biotechnology Vol.28 No.4

        Glycyrrhetic acid monoglucuronide (GAM) isobtained from the natural sweetener glycyrrhizin throughenzymolysis. Its sweetness concentration–response (C–R)behavior in room-temperature in water was determinedusing two-alternative forced choice discrimination tests. The C–R equation of resultant hyperbolic curve relatingsucrose equivalent (SE, %) to GAM concentration([GAM], mg/L) was SE = 19.6 9 [GAM]/(194.8 ? [GAM]). From the C–R function, Pw (2) ofGAM, relative to a 2% (w/v) sucrose reference, is morethan 900, which has much higher potency than its precursorglycyrrhizin. Molecular modeling showed that GAM isfinely bound into protein 1EWK through conventionalhydrogen bonds, p-Alkyl interactions and Van der Waalsbonds, which exhibited better protein inclusion than Glycyrrhizin. Thus, GAM could be developed

      • KCI등재

        Transparent Lamellar Porous Material and Its Greatly Reduced Dielectric Constant

        Lili Liu,Cuijiao Zhao,Yawen Huang,Xiaonan Wei,Hongtao Yu,Junxiao Yang 한국고분자학회 2017 Macromolecular Research Vol.25 No.10

        One trend for low dielectric materials is to reach low dielectric constant values at as low porosity as possible. In this work, a lamellar porous material was prepared by spin-coating of poly(vinyl alcohol) (PVA)/manganese dioxide (MnO2) nanosheet composited film, followed by cross-linking of PVA and removing nanosheets. FTIR, XRD and TGA measurement results demonstrate that the templates were almost completely removed. SEM image shows that the etched PVA film has a lamellar porous structure. Dielectric test results indicate that at the porosity of only 17.5%, the dielectric constant of porous PVA is reduced to approximately half that of neat cross-linked PVA. The serial model shows a good consistence with experimental dielectric constant value. This explains well the high efficiency of lamellar porous structure in reducing dielectric constant.

      • KCI등재

        Disease Course and Outcomes in Patients With the Limited Form of Neuromyelitis Optica Spectrum Disorders and Negative AQP4-IgG Serology at Disease Onset: A Prospective Cohort Study

        Xiao-Dong Li,Jing Zhou,Rui Li,Bingjun Zhang,Yuge Wang,Xiaonan Zhong,Yaqing Shu,Yanyu Chang,Wei Qiu 대한신경과학회 2022 Journal of Clinical Neurology Vol.18 No.4

        Background and Purpose Patients presenting with clinical characteristics that are strongly suggestive of neuromyelitis optica spectrum disorders (NMOSD) have a high risk of developing definite NMOSD in the future. Little is known about the clinical course, treatment, and prognosis of these patients with likely NMOSD at disease onset. Methods This study prospectively recruited and visited 24 patients with the limited form of NMOSD (LF-NMOSD) at disease onset from November 2012 to June 2021. Their demographics, clinical course, longitudinal aquaporin-4 immunoglobulin G (AQP4-IgG) serology, MRI, therapeutic management, and outcome data were collected and analyzed. Results The onset age of the cohort was 38.1±12.0 years (mean±standard deviation). The median disease duration was 73.5 months (interquartile range=44.3–117.0 months), and the follow-up period was 54.2±23.8 months. At the end of the last visit, the final diagnosis was categorized into AQP4-IgG-seronegative NMOSD (n=16, 66.7%), AQP4-IgG-seropositive NMOSD (n=7, 29.2%), or multiple sclerosis (n=1, 4.2%). Seven of the 24 patients (29.2%) experienced conversion to AQP4-IgG seropositivity, and the interval from onset to this serological conversion was 37.9±21.9 months. Isolated/mixed area postrema syndrome (APS) was the predominant onset phenotype (37.5%). The patients with isolated/mixed APS onset showed a predilection for conversion to AQP4-IgG seropositivity. All patients experienced a multiphasic disease course, with immunosuppressive therapy reducing the incidence rates of clinical relapse and residual functional disability. Conclusions Definite NMOSD may be preceded by LF-NMOSD, particularly isolated/ mixed APS. Intensive long-term follow-up and attack-prevention immunotherapeutic management is recommended in patients with LF-NMOSD.

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