1.Significance of Serum Galactomannan Detection in Invasive Pulmonary Aspergillosis Diagnosis
Erran LI ; Yanxia JIANG ; Kun WANG ; Yanling LI ; Jian KANG
Journal of China Medical University 2015;(10):865-869
Objective To evaluate the value of serum galactomannan (GM) detection for invasive pulmonary aspergillosis (IPA) diagnosis. Methods The suspicious IPA patients were divided into proven,clinical and possible IPA groups. The patients excluded of IPA were recruited as controls. The serum GM concentration was detected by Platelia Aspergillus double?sandwich enzyme linked immunosorbent assay(ELISA). Re?sults In the 103 patients,there were seven cases diagnosed as proven,nineteen cases diagnosed as clinical and forty cases diagnosed as possible IPA patients. Setting 0.5 as the optimal result for GM detection,the sensitivity,specificity,positive predictive values and negative predictive values of GM were 85.7%,86.5%,55%and 97%,respectively. In non?neutropenia patients combinded with the pulmonary chronic diseases,the sensitivity, specificity,positive predictive values and negative predictive values of GM detection were 71.4%,84.4%,66.75%and 87.1%,respectively. Conclu?sion Index>0.5 for GM test could increase the sensitivity without obvious decreased specificity. GM detection could provide valuable information in patients of non?neutropenia underlying the pulmonary chronic diseases,which had a better sensitivity and specificity versus conventional diagnostic tests.
2.Gastrointestinal mesenchymal tumors: a clinical pathologic and immunohistochemical study of 210 cases.
Zhi-Qiang WANG ; Shan WANG ; Ying-Jiang YE ; Yi-Long KANG ; Kun-Kun SUN ; Hong-Fang ZHENG
Chinese Journal of Gastrointestinal Surgery 2007;10(1):11-16
OBJECTIVETo study the clinical pathologic and immunohistochemical features of gastrointestinal mesenchymal tumors (GIMTs), and to investigate the value of molecular markers in GIMTs clinical differentiation diagnosis.
METHODSThe clinical and pathological data of 210 cases of GIMTs, collected from Jan. 1987 to Dec. 2005 in our hospital, were investigated retrospectively. GIMTs were rediagnosed by using standard immunostaining technique in paraffin-embedded tissue. The expression level of CD117, CD34, Desmin, SMA and PS100 were detected by immunohistochemical method.
RESULTSAmong 210 cases of GIMTs, 127 cases were Gastrointestinal stromal tumors (GISTs) (60.5%), 33 leiomyomas and leiomyosarcomas (15.7%), 27 neurogenic tumours (12.8%), and 23 miscellaneous tumors (11.0%). The incidences of GIST, leiomyoma and leiomyosarcoma were similar among men and women. Men were more likely to develop neurogenic tumors and miscellaneous tumors than women. Of all the GISTs, 51.2% cases originated from stomach, 19.7% from small intestine, 11.0% from esophagus, 10.2% from colon and rectum. The most common location of leiomyomas and leiomyosarcomas was esophagus (45.5%). The most common location of neurogenic tumors was retroperitoneum (74.1%). Common symptoms of GISTs included digestive tract hemorrhage in 36 cases (28.3%), abdominal pain in 27 cases (21.3%) and abdominal mass in 24 cases (18.9%). Other GIMT cases except GISTs had no first symptom of digestive tract hemorrhage. It was noticed that 79.5% of GISTs had no obvious invasion, and 72.7% of leiomyomas and leiomyosarcomas had no obvious invasion. 33.3% of neurogenic tumors invaded the adjacent organs or tissues. No metastases had been found in other GIMT cases except GISTs. The neoplastic cells of GISTs were composed of various percentage of spindle (72.5%), epithelioid (11.8%) and mixed-type cells (15.7%). The percentage of spindle cells in leiomyomas and leiomyosarcomas was 94. The immunohistochemical results of GISTs showed that the positive rate of CD117 was 93.7%, CD34 was 69.3%, Desmin was 13.4%, SMA was 12.6%, and PS100 was 10.2%. The immunohistochemical results of leiomyomas and leiomyosarcomas showed that the positive rate of Desmin was 78.5%, SMA was 63.6%, while as the expressions of CD117, CD34, and PS100 were negative. Diffuse strong positive staining of PS100 was observed in 88.9% of neurogenic tumor patients.
CONCLUSIONSGISTs are the most common tumors among GIMTs. GISTs are different from neurogenic tumors, leiomyomas and leiomyosarcomas in initial symptom, tumor location, biological behavior and immunophenotype. Immunohistochemistry plays an important role in differentiating GISTs from leiomyomas and neurogenic tumors.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers ; analysis ; Child ; Child, Preschool ; Female ; Gastrointestinal Neoplasms ; pathology ; Humans ; Immunohistochemistry ; Infant ; Male ; Mesenchymoma ; pathology ; Middle Aged ; Young Adult
3.Correlation of EGFR mutation with ERCC1 and TYMS mRNA expression in non-small cell lung cancer
Quan ZHANG ; Qunyou TAN ; Ruwen WANG ; Shaolin TAO ; Poming KANG ; Bo DENG ; Jinghai ZHOU ; Kun LI ; Kai QIAN ; Bin JIANG
Chongqing Medicine 2015;(9):1177-1179,1183
Objective To investigate whether EGFR gene mutations are correlated with the gene expression of ERCC1 and TYMS in non-small-cell lung cancer .Methods Collected February to December 2013 of non-small cell lung cancer(NSCLC) pa-tients eligible for enrolled 97 patients ,tumor tissue specimens obtained by intraoperative cut or puncture ,Gene expression of ERCC1 and TYMS were determined by branched-DNA liquid chip ,while somatic mutations in EGFR(E18 ,E19 ,E20 ,E21) gene were detec-ted by xTAG-liquid chip;And analysis of EGFR gene mutation associated with ERCC1 ,TYMS mRNA expression .Results Totally 29 cases of EGFR mutation were detected in all 97 specimens ,with a mutation rate of 30% (29/97) ,and a relatively high detection rate was observed in female ,adenocarcinoma and non-smoking patients(P<0 .05) .EGFR mutation was relevant to the expression of ERCC1(χ2 =4 .088 ,P<0 .05) ,EGFR mutation was irrelevant to the expression of TYMS(χ2 =0 .265 ,P>0 .05) .Conclusion In NSCLC tissues ,EGFR mutation is relevant to the expression of ERCC1 but irrelevant to the expression of TYMS .
4.Preliminary study on aberrant expression of miRNAs related to the formation of the distinction between pediatric and adult types of brainstem gliomas.
Xuan WANG ; Hong-wei ZHANG ; An-ling ZHANG ; Lei HAN ; Kun WANG ; Pei-yu PU ; Chang-hong SHEN ; Chun-sheng KANG ; Chun-jiang YU
Chinese Journal of Surgery 2012;50(11):1015-1020
OBJECTIVESTo study the different expression of miRNA between pediatric and adult types of brainstem gliomas, and to provide the target miRNAs for explore the mechanism and miRNA interference of the malignant progression of pediatric BSG.
METHODSmiRNA expression profiles in orthotopic models which could simulate the BSG heterogeneity were examined by microarray and analyzed to obtain the aberrantly expressed miRNAs. The two types of human BSG tissue were utilized to verify the microarray data by qRT-PCR and in situ hybridization for the putative causative miRNAs.
RESULTSThere were 216 miRNAs detected in both the pediatric BSG group and the adult BSG group, 39 miRNAs to be differential expressed in the pediatric BSG group versus adult group, including 10 up-regulated and 29 down-regulated. qRT-PCR and in situ hybridization indicated good consistency with that of the microarray method.
CONCLUSIONSAberrantly expressed miRNA may serve as putative causative involvement of malignant progression of pediatric BSG, thereby might be potentially novel targets for therapy.
Adult ; Age Factors ; Animals ; Brain Stem ; Brain Stem Neoplasms ; metabolism ; Child ; Disease Models, Animal ; Female ; Gene Expression Profiling ; Glioma ; metabolism ; Humans ; In Situ Hybridization ; MicroRNAs ; metabolism ; Oligonucleotide Array Sequence Analysis ; Rats
5.Establishment of Quality Control System of Nucleic Acid Detection for Ebola Virus in Sierra Leone-China Friendship Biological Safety Laboratory.
Qin WANG ; Yong ZHANG ; Kai NIE ; Huanyu WANG ; Haijun DU ; Jingdong SONG ; Kang XIAO ; Wenwen LEI ; Jianqiang GUO ; Hejiang WEI ; Kun CAI ; Yanhai WANG ; Jiang WU ; Bangura GERALD ; Idrissa Laybohr KAMARA ; Mifang LIANG ; Guizhen WU ; Xiaoping DONG
Chinese Journal of Virology 2016;32(2):210-214
The quality control process throughout the Ebola virus nucleic acid detection in Sierra Leone-China Friendship Biological Safety Laboratory (SLE-CHN Biosafety Lab) was described in detail, in order to comprehensively display the scientific, rigorous, accurate and efficient practice in detection of Ebola virus of first batch detection team in SLE-CHN Biosafety Lab. Firstly, the key points of laboratory quality control system was described, including the managements and organizing, quality control documents and information management, instrument, reagents and supplies, assessment, facilities design and space allocation, laboratory maintenance and biosecurity. Secondly, the application of quality control methods in the whole process of the Ebola virus detection, including before the test, during the test and after the test, was analyzed. The excellent and professional laboratory staffs, the implementation of humanized management are the cornerstone of the success; High-level biological safety protection is the premise for effective quality control and completion of Ebola virus detection tasks. And professional logistics is prerequisite for launching the laboratory diagnosis of Ebola virus. The establishment and running of SLE-CHN Biosafety Lab has landmark significance for the friendship between Sierra Leone and China, and the lab becomes the most important base for Ebola virus laboratory testing in Sierra Leone.
China
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Ebolavirus
;
classification
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genetics
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isolation & purification
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Hemorrhagic Fever, Ebola
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diagnosis
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virology
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Humans
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Laboratories
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manpower
;
standards
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Laboratory Infection
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Quality Control
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RNA, Viral
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genetics
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Sierra Leone
6.Classified reduction based on CT two-dimensional images for the surgical treatment of single segment facet joint dislocation in subaxial cervical spine
Yongsheng KANG ; Wei MEI ; Qingde WANG ; Rundong GUO ; Peilin LIU ; Wentao JIANG ; Zhenhui ZHANG ; Kai SU ; Zhe SHAO ; Ya SONG ; Kun WANG
Chinese Journal of Trauma 2023;39(4):331-340
Objective:To investigate the efficacy of the classified reduction based on CT two-dimensional images for the surgical treatment of single segment facet joint dislocation in subaxial cervical spine.Methods:A retrospective case series study was made on 105 patients with single segment facet joint dislocation in subaxial cervical spine admitted to Zhengzhou Orthopedic Hospital from January 2015 to October 2022. There were 63 males and 42 females, with the age range of 22-78 years [(47.5±3.6)years]. Preoperative American Spinal Cord Injury Association (ASIA) classification was grade A in 23 patients, grade B in 45, grade C in 22, grade D in 15 and grade E in 0. The classification of surgical approach was based on the presence or not of continuity between anterior and posterior subaxial cervical structures and the movability of the posterior cervical facet joint on CT two-dimensional images, including anterior cervical surgery if both were presented and posterior facet joint resection plus anterior cervical surgery if there was discontinuity between anterior and posterior subaxial cervical structures or posterior facet joint fusion. Reduction procedures were applied in accordance with the type of facet joint dislocation classified based on the position of the lower upper corner of facet joint, including skull traction or manipulative reduction for the dislocation locating at the dorsal side (type A), intraoperative skull traction and leverage technique for the dislocation locating at the top (type B) and intraoperative skull traction and leverage technique with boosting for the dislocation locating at the ventral side (type C). If the dislocation of two facet joints in the same patient was different, the priority of management followed the order of type C, type B and type A. The reduction success rate, operation time and intraoperative blood loss were recorded. The cervical physiological curvature was evaluated by comparing the intervertebral space height and Cobb angle before operation, at 3 months after operation and at the last follow-up. The fusion rate of intervertebral bone grafting was evaluated by Lenke grading at 3 months after operation. The spinal cord nerve injury was assessed with ASIA classification before operation and at 3 months after operation. Japanese Orthopedic Association (JOA) score was applied to measure the degree of cervical spinal cord dysfunction before operation and at 3 months after operation, and the final follow-up score was used to calculate the rate of spinal cord functional recovery. The occurrence of complications was observed.Results:All patients were followed up for 3-9 months [(6.0±2.5)months]. The reduction success rate was 100%. The operation time was 40-95 minutes [(58.6±9.3)minutes]. The intraoperative blood loss was 40 to 120 ml [(55.7±6.8)ml]. The intervertebral space height was (4.7±0.3)mm and (4.7±0.2)mm at 3 months after operation and at the last follow-up, significantly decreased from preoperative (3.1±0.5)mm (all P<0.01), but there was no significant difference in intervertebral space height at 3 months after operation and at the last follow-up ( P>0.05). The Cobb angle was (6.5±1.3)° and (6.3±1.2)° at 3 months after operation and at the last follow-up, significantly increased from preoperative (-5.4±2.2)° (all P<0.01), but there was no significant difference in Cobb angle at 3 months after operation and at the last follow-up ( P>0.05). The fusion rate of intervertebral bone grafting evaluated by Lenke grading was 100% at 3 months after operation. The ASIA grading was grade A in 15 patients, grade B in 42, grade C in 29, grade D in 12 and grade E in 7 at 3 months after operation. The patients showed varying degrees of improvement in postoperative ASIA grade except that 15 patients with preoperative ASIA grade A had partial recovery of limb sensation but no improvement in ASIA grade. The JOA score was (13.3±0.6)points and (13.1±0.6)points at 3 months after operation and at the last follow-up, significantly improved from preoperative (6.8±1.4)points (all P<0.01), but there was no significant difference in JOA score at 3 months after operation and at the last follow-up ( P>0.05). The rate of spinal cord functional recovery was (66.3±2.5)% at the last follow-up. All patients had no complications such as increased nerve damage or vascular damage. Conclusion:The classified reduction based on CT two-dimensional images for the surgical treatment of single segment facet joint dislocation in subaxial cervical spine has advantages of reduced facet joint dislocation, recovered intervertebral space height and physiological curvature, good intervertebral fusion and improved spinal cord function.
7.Changes of T-cell clonality after induction-cultivation of peripheral T lymphocytes in adoptive immunotherapy for leukemias.
Yan LIU ; Jiang-Ying GU ; Yuan OU ; Mian-Yang LI ; He WANG ; Xian JIN ; Xiu-Yan TAO ; Zhao-Li LIU ; Xing-Fan MA ; Xiu-Li WANG ; Si-Kun MA ; Rui KANG ; Peng CAI ; Chun-Rong TONG ; Ping ZHU
Journal of Experimental Hematology 2009;17(3):621-626
This study was purposed to analyze the changes of T-cell clonality after induction of peripheral T lymphocytes by autogenous DC and cytokines in the preparation of adoptive immunotherapy for leukemias. The bone marrow and peripheral blood from 21 leukemia patients at remission stage after treatment and subjected to adoptive immunotherapy were collected. Their DCs and T-cells were stimulated with cytokines and then were mixed to activate T-cells. T-cell receptor beta variable region (TCRBV) families were amplified by RT-PCR, and genescan method and sequencing of the PCR products were used to observe the clonality changes of T-cells before and after the induction and cultivation of T-cells. The flow cytometry was used to identify CD3(+), CD4(+), CD8(+), CD3(+)CD56(+) and CD4(+)CD25str(+)FOXP3(+) cells to disclose the ratio change of cytotoxic T lymphocytes (CTL), helper T-cells, regulatory T-cells and NK T-cells before and after induction and cultivation of T-cells. The results showed that in the 21 patients, most of the 24 TCRBV families presented as oligoclonal distribution on genescan, several families were not expressed, and only a few families remained polyclonal. TCRBV24 was found to be oligoclonal in all of the 21 patients. DNA sequence analysis of TCRBV24 revealed a common motif of VAG in CDR3 in 3 cases and a common motif of GGG in CDR3 in 2 cases. In patient 5, both TCRBV 24 and TCRBV8 contained the same motif of GGG in CDR3. The identical motif in these patients may suggest that these T-cells recognize the same antigen. The peripheral lymphocytes demonstrated recovery of clonal profile on genescan from oligoclonal profile and absence of several families before the induction and cultivation to typical polyclonal profile in all TCRBV families after the induction by DC and cytokines for 13 days. After the induction and cultivation, the number of lymphocytes increased to 3.38 +/- 1.20 times. CD3(+), CD4(+), CD8(+), CD3(+)CD56(+) and CD4(+)CD25str(+)FOX P3(+) cells were 71.1 +/- 11.8%, 26.7 +/- 11.4%, 35.7 +/- 12.9%, 3.1 +/- 1.6% and 0.12 +/- 0.1% respectively before the induction and cultivation, and changed to 95.4 +/- 3.2% (p < 0.01), 27.0 +/- 13.1% (p > 0.01), 55.5 +/- 13.8% (p < 0.01), 9.8 +/- 6.1% (p < 0.01) and 0.22 +/- 0.18% (p < 0.01) respectively after the induction and cultivation. It is concluded that the major action of this induction and cultivation method on T-lymphocytes in vitro is the promotion of CTL and NK T-cell proliferation. In leukemic patients at the remission stage, the TCRBV profile is characterized by the oligoclonal proliferation of T-lymphocytes. Several proliferated clones may have the same motif in CDR3, suggesting the recognition of the same antigen by these lymphocyte clones. Cytokine induction and co-culture with autogenous DCs can stimulate the T-lymphocytes to recover their immunocompetence as manifested by the polyclonal profile and the proliferation of CTL and NK-T cells.
Adolescent
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Adult
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Aged
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Child
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Female
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Genes, T-Cell Receptor beta
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Humans
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Immunotherapy, Adoptive
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Leukemia
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genetics
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immunology
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therapy
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Lymphocyte Activation
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Male
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Middle Aged
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T-Lymphocytes
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chemistry
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cytology
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immunology
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T-Lymphocytes, Cytotoxic
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immunology
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T-Lymphocytes, Regulatory
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chemistry
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immunology
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Young Adult
8.Medicinal chemistry strategies in seeking coronavirus inhibitors
Jing LI ; Xiang-yi JIANG ; Shu-jing XU ; Qing-hua CUI ; Rui-kun DU ; Dong-wei KANG ; Peng ZHAN ; Li-jun RONG ; Xin-yong LIU
Acta Pharmaceutica Sinica 2020;55(4):537-553
The epidemic caused by coronavirus poses a serious threat to human health, but there is no specific drug or vaccine for the treatment of this kind of virus infection. Herein, this article selects typical case studies in recent years and reviews the medicinal chemistry strategies of anti-SARS-CoV, MERS-CoV and other coronavirus drugs from the perspective of medicinal chemistry, and tries to provide some clues to current drug research againstSARS-CoV-2.
9.Overexpression of NAT10 induced platinum drugs resistance in breast cancer cell.
Pan QI ; Ya Ke CHEN ; Rui Li CUI ; Rui Juan HENG ; Sheng XU ; Xiao Ying HE ; Ai Min YUE ; Jiang Kun KANG ; Hao Han LI ; Yong Xin ZHU ; Cong WANG ; Yu Lu CHEN ; Kua HU ; Yan Yan YIN ; Li Xue XUAN ; Yu SONG
Chinese Journal of Oncology 2022;44(6):540-549
Objective: To observe the platinum drugs resistance effect of N-acetyltransferase 10 (NAT10) overexpression in breast cancer cell line and elucidate the underlining mechanisms. Methods: The experiment was divided into wild-type (MCF-7 wild-type cells without any treatment) group, NAT10 overexpression group (H-NAT10 plasmid transfected into MCF-7 cells) and NAT10 knockdown group (SH-NAT10 plasmid transfected into MCF-7 cells). The invasion was detected by Transwell array, the interaction between NAT10 and PARP1 was detected by co-immunoprecipitation. The impact of NAT10 overexpression or knockdown on the acetylation level of PARP1 and its half-life was also determined. Immunostaining and IP array were used to detect the recruitment of DNA damage repair protein by acetylated PARP1. Flow cytometry was used to detect the cell apoptosis. Results: Transwell invasion assay showed that the number of cell invasion was 483.00±46.90 in the NAT10 overexpression group, 469.00±40.50 in the NAT10 knockdown group, and 445.00±35.50 in the MCF-7 wild-type cells, and the differences were not statistically significant (P>0.05). In the presence of 10 μmol/L oxaliplatin, the number of cell invasion was 502.00±45.60 in the NAT10 overexpression group and 105.00±20.50 in the NAT10 knockdown group, both statistically significant (P<0.05) compared with 219.00±31.50 in wild-type cells. In the presence of 10 μmol/L oxaliplatin, NAT10 overexpression enhanced the binding of PARP1 to NAT10 compared with wild-type cells, whereas the use of the NAT10 inhibitor Remodelin inhibited the mutual binding of the two. Overexpression of NAT10 induced PARP1 acetylation followed by increased PARP1 binding to XRCC1, and knockdown of NAT10 expression reduced PARP1 binding to XRCC1. Overexpression of NAT10 enhanced PARP1 binding to LIG3, while knockdown of NAT10 expression decreased PARP1 binding to LIG3. In 10 μmol/L oxaliplatin-treated cells, the γH2AX expression level was 0.38±0.02 in NAT10 overexpressing cells and 1.36±0.15 in NAT10 knockdown cells, both statistically significant (P<0.05) compared with 1.00±0.00 in wild-type cells. In 10 μmol/L oxaliplatin treated cells, the apoptosis rate was (6.54±0.68)% in the NAT10 overexpression group and (12.98±2.54)% in the NAT10 knockdown group, both of which were statistically significant (P<0.05) compared with (9.67±0.37)% in wild-type cells. Conclusion: NAT10 overexpression enhances the binding of NAT10 to PARP1 and promotes the acetylation of PARP1, which in turn prolongs the half-life of PARP1, thus enhancing PARP1 recruitment of DNA damage repair related proteins to the damage sites, promoting DNA damage repair and ultimately the survival of breast cancer cells.
Breast Neoplasms/enzymology*
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Cell Line, Tumor
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Drug Resistance, Neoplasm
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Female
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Humans
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MCF-7 Cells
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N-Terminal Acetyltransferases/metabolism*
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Organoplatinum Compounds/pharmacology*
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Oxaliplatin/pharmacology*
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X-ray Repair Cross Complementing Protein 1
10.Related factors of negative conversion time of nucleic acid in children with COVID-19.
Yu Feng LI ; Jian Hua ZHANG ; Han GAN ; Kai Chuang ZHANG ; Kang CAI ; Wei LIU ; Sheng Nan LUO ; Hong Li JIANG ; Biao JIN ; Li Bin ZHAO ; Kun SUN
Chinese Journal of Pediatrics 2023;61(3):256-260
Objective: To explore the related factors of negative conversion time (NCT) of nucleic acid in children with COVID-19. Methods: A retrospective cohort study was conducted. A total of 225 children who were diagnosed with COVID-19 and admitted to Changxing Branch of Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from April 3rd to May 31st 2022 were enrolled in the study. The infection age, gender, viral load, basic disease, clinical symptoms and information of accompanying caregivers were retrospectively analyzed. According to age, the children were divided into<3 years of age group and 3-<18 years of age group. According to the viral nucleic acid test results, the children were divided into positive accompanying caregiver group and negative accompanying caregiver group. Comparisons between groups were performed using Mann-Whitney U test or Chi-square test. Multivariate Logistic regression analysis was used to analyze the related factors of NCT of nucleic acid in children with COVID-19. Results: Among the 225 patients (120 boys and 105 girls) of age 2.8 (1.3, 6.2) years, 119 children <3 years and 106 children 3-<18 years of age, 19 cases were diagnosed with moderate COVID-19, and the other 206 cases were diagnosed with mild COVID-19. There were 141 patients in the positive accompanying caregiver group and 84 patients in the negative accompanying caregiver group.Patients 3-<18 years of age had a shorter NCT (5 (3, 7) vs.7 (4, 9) d, Z=-4.17, P<0.001) compared with patients <3 years of age. Patients in the negative accompanying caregiver group had a shorter NCT (5 (3, 7) vs.6 (4, 9) d,Z=-2.89,P=0.004) compared with patients in the positive accompanying caregiver group. Multivariate Logistic regression analysis showed that anorexia was associated with NCT of nucleic acid (OR=3.74,95%CI 1.69-8.31, P=0.001). Conclusion: Accompanying caregiver with positive nucleic acid test may prolong NCT of nucleic acid, and decreased appetite may be associated with prolonged NCT of nucleic acid in children with COVID-19.
Adolescent
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Child
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Child, Preschool
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Female
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Humans
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Male
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Young Adult
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China/epidemiology*
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COVID-19/genetics*
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Nucleic Acids
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Retrospective Studies