Pan-cancer Analysis of Tumor Mutational Burden and Homologous Recombination DNA Damage Repair Using Targeted Next-Generation Sequencing

Hai-Yun Wang,Ling Deng,Ying-Qing Li,Xiao Zhang,Ya-Kang Long,Xu Zhang,Yan-Fen Feng,Yuan He,Tao Tang,Xin-Hua Yang,Fang Wang 대한암학회 2021 Cancer Research and Treatment Vol.53 No.4

Purpose Current variability in methods for tumor mutational burden (TMB) estimation and reporting demonstrates the urgent need for a homogeneous TMB assessment approach. Here, we compared TMB distributions in different cancer types using two customized targeted panels commonly used in clinical practice. Materials and Methods TMB spectra of 295- and 1021-gene panels in multiple cancer types were compared using targeted next-generation sequencing (NGS). The TMB distributions across a diverse cohort of 2,332 cancer cases were then investigated for their associations with clinical features. Treatment response data were collected for 222 patients who received immune-checkpoint inhibitors (ICIs) and their homologous recombination DNA damage repair (HR-DDR) and programmed death-ligand 1 (PD-L1) expression were additionally assessed and compared with the TMB and response rate. Results The median TMB between gene panels was similar despite a wide range in TMB values. The highest TMB was eight and 10 in patients with squamous cell carcinoma and esophageal carcinoma according to the classification of histopathology and cancer types, respectively. Twenty-three out of 103 patients (22.3%) were HR-DDR–positive and could benefit from ICI therapy; out of those 23 patients, seven patients had high TMB (p=0.004). Additionally, PD-L1 expression was not associated with TMB or treatment response among patients receiving ICIs. Conclusion Targeted NGS assays demonstrated the ability to evaluate TMB in pan-cancer samples as a tool to predict response to ICIs. In addition, TMB integrated with HR-DDR–positive status could be a significant biomarker for predicting ICI response in patients.

은(I)화합물:비스(디프로필디싸이오포스페이토)비스(1,10-펜안트로린)이온(I);Ag₂[Phen]₂[S₂P(OPr)₂]₂

Fang Fang Jian,Hai Lian Xiao,Huan Xiang Wang,Kui Jiao Korean Chemical Society 2003 대한화학회지 Vol.47 No.1

이핵 화합물, $Ag_2$[Phen]_2[S_2P(OPr)_2]_2$(Phen=1,10-phenanthroline; Pr=propyl)은 비스(디프로필디싸이오포스페이토) 은(|)화합물과 1,10 펜안트로린 리간드 반응에 의하여 합성되었고, 그 화합물 구조는 X-ray에 의하여 규명되었다. 두 디프로필디싸이오포스페이토 리간드는 두 개의 은 원자를 연결하여 팔각형 $Ag_2S_4P_2$ 고리를 형성하였고, 1,10-펜안트로린 리간드는 은 이온과 결합하여 사면체구조를 이루었다. Ag-S 결합거리는 2.471(1)와 2.567(1) ${\AA}$이었고, Ag-N 결합 거리는 2.3666(3)와 2.471(3) ${\AA}$이었다. The dinuclear $Ag_2[Phen]_2[S_2P(OPr)_2]_2$(phen=1,10-phenanthroline; Pr=propyl), was prepared by the reaction of bis(dipropyldithiophosphato) silver(I) complex with 1,10-phenanthroline ligand, and its structure was determined by X-ray crystallography. The two dipropyldithiophosphato ligands each bridge two silver atoms to form an eight-membered $Ag_2S_4P_2$ ring, while the 1,10-phenanthroline molecule coordinates to a silver atom to complete the local tetrahedral geometry for the metal ion. The Ag-S bond distances are 2.559(1) and 2.567(1)${\AA}$, and the Ag-N bond distances are 2.366(3) and 2.471(3)${\AA}$.

Risk Factors for Anxiety in Major Depressive Disorder Patients

Li-Min Xin,Lin Chen,Zhen-Peng Ji,Suo-Yuan Zhang,Jun Wang,Yan-Hong Liu,Da-Fang Chen,Fu-De Yang,Gang Wang,Yi-Ru Fang,Zheng Lu,Hai-Chen Yang,Jian Hu,Zhi-Yu Chen,Yi Huang,Jing Sun,Xiao-Ping Wang,Hui-Chun 대한정신약물학회 2015 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.13 No.3

Objective: To analyze the sociodemographic and clinical factors related to anxiety in patients with major depressive disorder (MDD). Methods: This study involved a secondary analysis of data obtained from the Diagnostic Assessment Service for People with Bipolar Disorders in China (DASP), which was initiated by the Chinese Society of Psychiatry (CSP) and conducted from September 1, 2010 to February 28, 2011. Based on the presence or absence of anxiety-related characteristics, 1,178 MDD patients were classified as suffering from anxious depression (n=915) or non-anxious depression (n=263), respectively. Results: Compared with the non-anxious group, the anxious-depression group had an older age at onset (t=−4.39, p<0.001), were older (t=−4.69, p<0.001), reported more lifetime depressive episodes (z=−3.24, p=0.001), were more likely to experience seasonal depressive episodes (χ2=6.896, p=0.009) and depressive episodes following stressful life events (χ2=59.350, p <0.001), and were more likely to have a family history of psychiatric disorders (χ2=6.091, p=0.014). Their positive and total scores on the Mood Disorder Questionnaire (MDQ) and the 32-item Hypomania Checklist (HCL-32) (p<0.05) were also lower. The logistic regression analysis indicated that age (odds ratio [OR]=1.03, p<0.001), a lower total MDQ score (OR=0.94, p=0.011), depressive episodes following stressful life events (OR=3.04, p<0.001), and seasonal depressive episodes (OR=1.75, p=0.039) were significantly associated with anxious depression. Conclusion: These findings indicate that older age, fewer subclinical bipolar features, an increased number of depressive episodes following stressful life events, and seasonal depressive episodes may be risk factors for anxiety-related characteristics in patients with MDD.

5,10-Methylenetetrahydrofolate Reductase Polymorphisms and Colon Cancer Risk: a Meta-analysis

Fang, Xin-Yu,Xu, Wang-Dong,Huang, Qian,Yang, Xiao-Ke,Liu, Yan-Yan,Leng, Rui-Xue,Pan, Hai-Feng,Ye, Dong-Qing Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.19

Previous studies investigating the association between 5,10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and colon cancer risk have generated conflicting results. The aim of our meta-analysis was to clarify the precise association. A systematic literature search was conducted to identify all relevant studies. Pooled odds ratio (ORs) with 95% confidence interval (CI) were used to estimate the strength of the association. In this meta-analysis, a total of 13 articles, involving 5,386 cases and 8,017 controls met the inclusion criteria. Overall, a significant association was found between colon cancer risk and the MTHFR C667 polymorphism (TT vs CC+CT: OR=0.79; 95%CI=0.65-0.96; p=0.017). Stratification by ethnicity revealed that MTHFRC667 was associated with colon cancer risk in the non-Asian group (TT vs CC+CT:OR=0.77, 95%CI=0.68-0.89, p=0.000; TT vs CC: OR=0.84, 95%CI=0.73-0.97, p=0.016). Stratification by source of control indicated that MTHFR C667 also correlated with colon cancer risk in the population-based subgroup (TT vs CC: OR=0.85, 95%CI=0.74-0.97, p=0.017; TT vs CC+CT: OR=0.78, 95%CI=0.68-0.89, p=0.000) and hospital-based subgroup (TT vs CC+CT: OR=0.65, 95%CI=0.49-0.86, p=0.003). However, risk was significantly increased for MTHFR A1298C polymorphisms and colon cancer risk in hospital-based studies (C vs A: OR=1.52, 95%CI=1.26-1.83, p=0.000; CC+AC vs AA: OR=1.93, 95%CI=1.47-2.49, p=0.000) but reduced in population-based studies (CC vs AA: OR=0.83, 95%CI=0.70-0.99, p=0.042). In conclusion, the results of our meta-analysis suggest that the MTHFR C667 polymorphism is associated with reduced colon cancer risk, especially for non-Asian populations.

Multiple Impairments in Male Reproduction 1 (mimr1), a Novel Male-Sterile Mutant of Arabidopsis thaliana, Shows Several Defects in Male Reproductive Development

Hai-Yan Chen,Yue-Feng Guan,Xue-Yong Huang,Yu-Ting Wu,Fen-Fei Wang,Ju-Fang Gao,Que Zhou,Zhong-Nan Yang,Jia-Yao Liu,Hong-Xia Zhang 한국식물학회 2012 Journal of Plant Biology Vol.55 No.3

We have characterized a new male-sterile mutant in Arabidopsis that exhibits conditional sterility but has restored fertility when drought-stressed. This mutant,multiple impairments in male reproduction 1 (mimr1),shows pleiotropic defects in both vegetative and reproductive development. Examination with dissecting and scanning electron microscopes revealed that its pollen grains are not effectively released from the anther locule after dehiscence, and anther differentiation is defective. Growth of the style and stamen filaments are also abnormal. Histological analysis demonstrated that these phenomena are due not only to a noticeably reduced extension of the stamen but also greater elongation of the pistil. Genetic analysis indicated that mimr1 is a single locus recessive nuclear mutant. The mutation can be mapped to a locus strongly linked to a 1200-kb region on Chromosome 3. Meta-analysis of expression patterning presented several candidate genes in that region. No mutants with similar phenotypes have previously been reported, suggesting that mimr1 is a novel male-sterile locus. Characterization of MIMR1 will provide further insights into the molecular basis for the development of plant reproductive organs.

Gut Microbiota Community and Its Assembly Associated with Age and Diet in Chinese Centenarians

( Fang Wang ),( Ting Yu ),( Guo Hong Huang ),( Da Cai ),( Xiaolin Liang ),( Hai Yan Su ),( Zhenjun Zhu ),( Danlei Li ),( Yang Yang ),( Pei Hong Shen ),( Rui Feng Mao ),( Lian Yu ),( Mou Ming Zhao ),( 한국미생물 · 생명공학회 2015 Journal of microbiology and biotechnology Vol.25 No.8

Increasing evidence suggests that gut microbiota underpin the development of health and longevity. However, our understanding of what influences the composition of this community of the longevous has not been adequately described. Therefore, illumina sequencing analysis was performed on the gut microbiota of centenarians (aged 100-108 years; RC) and younger elderlies (aged 85-99 years; RE) living in Bama County, Guangxi, China and the elderlies (aged 80-92 years; CE) living in Nanning City, Guangxi, China. In addition, their diet was monitored using a semiquantitative dietary questionary (FFQ 23). The results revealed the abundance of Roseburia and Escherichia was significantly greater, whereas that of Lactobacillus, Faecalibacterium, Parabacteroides, Butyricimonas, Coprococcus, Megamonas, Mitsuokella, Sutterella, and Akkermansia was significantly less in centenarians at the genus level. Both clustering analysis and UniFraq distance analysis showed structural segregation with age and diet among the three populations. Using partial least square discriminate analysis and redundancy analysis, we identified 33 and 34 operational taxonomic units (OTUs) as key OTUs that were significantly associated with age and diet, respectively. Age-related OTUs were characterized as Ruminococcaceae, Clostridiaceae, and Lachnospiraceae, and the former two were increased in the centenarians; diet-related OTUs were classified as Bacteroidales, Lachnospiraceae, and Ruminococcaceae. The former two were deceased, whereas the later one was increased, in the high-fiber diet. The age and high-fiber diet were concomitant with changes in the gut microbiota of centenarians, suggesting that age and high-fiber diet can establish a new structurally balanced architecture of gut microbiota that may benefit the health of centenarians.

Case Report : Nutrition Therapy for Mitochondrial Neurogastrointestinal Encephalopathy with Homozygous Mutation of the TYMP Gene

( Jing Wang ),( Wei Chen ),( Fang Wang ),( Dong Wu ),( Jia Ming Qian ),( Jun Ren Kang ),( Hai Long Li ),( En Ling Ma ) 한국임상영양학회 2015 Clinical Nutrition Research Vol.4 No.2

Mitochondrial neurogastrointestinal encephalopathy (MNGIE) is characterized by significant gastrointestinal dysmotility. Early and long-term nutritional therapy is highly recommended. We report a case of MNGIE in a patient who was undergoing longterm nutrition therapy. The patient was diagnosed with a serious symptom of fatty liver and hyperlipidemia complications, along with homozygous mutation of the thymidine phosphorylase (TYMP) gene (c.217G > A). To our knowledge, this is the first report of such a case. Herein, we describe preventive measures for the aforementioned complications and mitochondrial disease-specific nutritional therapy.

Preparation of lithium-doped NaV6O15 thin film cathodes with high cycling performance in SIBs

Xu Hai-Yan,Ruan Jun Hai,Liu Fang Lin,Li Dong-Cai,Zhang Feng-Jun,Wang Ai-Guo,Sun Dao-Sheng,오원춘 한국세라믹학회 2022 한국세라믹학회지 Vol.59 No.3

Lithium ions-doped NaV6O15 thin films have been prepared using a simple low temperature liquid phase deposition method and subsequent annealing process. X-ray diffraction (XRD), Fourier transform infrared spectrometer (FTIR), scanning elec- tron microscopy (SEM), and photoelectron spectroscopy (XPS) have been used to study the structural and physicochemical characteristics of the NaV6O15 film. The films were grown on the FTO conductive glass and used directly as an electrode of sodium ion batteries. The prepared lithium ions-doped NaV6O15 thin film electrodes showed an excellent cycling stability and discharge capacity, which may be attributed to the stability of the Li+ embedded into the gap between the V–O layers to maintain the structure and its stable β-phase structure transformed after the first cycle. The cycling stability greatly improved with increasing annealing temperature, while the discharge capacity decreased. The capacities of the film electrodes annealed at 400 °C and 450 °C maintained above 97% after 100 cycles. The lithium-doped NaV6O15 underwent a phase transition dur- ing the first charge/discharge cycle. The new transformed phase has perfect crystal structure stability undergoing insertion and deinsertion of Na+. Therefore, the lithium-doped NaV6O15 thin film possesses good cycling stability and is expected to be a promising thin film cathode for sodium-ion batteries.

Reports ; Adrenergic receptor β2 activation by stress promotes breast cancer progression through macrophages M2 polarization in tumor microenvironment

( Jun-fang Qin ),( Feng-jiao Jin ),( Ning Li ),( Hai-tao Guan ),( Lan Lan ),( Hong Ni ),( Yue Wang ) 생화학분자생물학회 2015 BMB Reports Vol.48 No.5

Stress and its related hormones epinephrine (E) and norepinephrine (NE) play a crucial role in tumor progression. Macrophages in the tumor microenvironment (TME) polarized to M2 is also a vital pathway for tumor deterioration. Here, we explore the underlying role of macrophages in the effect of stress and E promoting breast cancer growth. It was found that the weight and volume of tumor in tumor bearing mice were increased, and dramatically accompanied with the rising E level after chronic stress using social isolation. What is most noteworthy, the number of M2 macrophages inside tumor was up-regulated with it. The effects of E treatment appear to be directly related to the change of M2 phenotype is reproduced in vitro. Moreover, E receptor ADRβ2 involved in E promoting M2 polarization was comprehended simultaneously. Our results imply psychological stress is influential on specific immune system, more essential for the comprehensive treatment against tumors. [BMB Reports 2015; 48(5): 295-300]

Experimental Study on Magnesium Sulfate Cement Concrete Splices of Widened Box Girder

Li-fang Zhang,Jun Yan,Hai-yan Ma,Hong-fa Yu,Ying Wang,Qi-quan Mei 대한토목학회 2021 KSCE JOURNAL OF CIVIL ENGINEERING Vol.25 No.12

The connecting part of bridge widening undertakes complicated forces and tends to crack. Basic magnesium sulfate cement concrete has excellent properties such as ideal early strength and tensile strength, meeting the performance requirements of joint materials. Experiments of two spliced box girder specimens with C40 basic magnesium sulfate cement concrete (MC) and normal Portland cement concrete (NC) as joint materials are carried out. Concrete strain, reinforcement strain, deflection and crack propagation law of the joint section are tested and analyzed under symmetrical loading at the cantilever of the box girders. The study shows when MC material is used in the splicing section, the joint section showed a multi-cracks failure mode with an ultimate load ratio of 0.99 and a maximum crack width of 1.3 mm; NC joint section has only three longitudinal cracks with an ultimate load ratio of 0.97 and a maximum crack width of 0.98 mm. Under the same load, the crack width and the deflection of mid-span MC joint section are greater than which of NC joint section. The maximum deflection of NC splicing section is 1.20 mm, which is 1/633 of the calculating span length. The maximum deflection of MC spliced section is 2.03 mm, which is 1/374 of the calculating span length. Comparison of the maximum deflection and the maximum crack width shows that MC material has better ductility.