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142,573 cases of hepatectomy in China: a multicenter retrospective investigation显示文摘Hepatectomy is currently routinely performed in most hospitals in China. China owns the largest population of liver diseases and the biggest number of liver resection cases. A nationwide multicenter retrospective investigation involving 112 hospitals was performed, and focused on liver resection for patients with hepatocellular carcinoma(HCC). 42,573 cases of hepatectomy were enrolled, and 18,275 valid cases of liver resection for HCC patients were selected for statistical analysis. The epidemiology of HCC, distribution of hepatectomy, postoperative complications and prognosis were finally analyzed. In the 18,275 HCC patients,81% had hepatitis B virus infection and 10% had hepatitis C virus infection. 38% of the HCC patients had normal Alphafetoprotein(AFP) level, and other 35% had an AFP level lower than 400 ng mL^(-1). In the study period, 97% of the hepatectomy for HCC were treated with open surgery, and 23.81% had vascular exclusion techniques. The operation time was(191.7±105.6) min,the blood loss was(546.0±562.8) m L, and blood transfusion was(543.0±1,035.2) m L. The median survival for HCC patients was 631 days, with 1-, 3-, and 5-year overall survival of 73.2%, 28.8% and 19.6%, respectively. Liver cirrhosis, multiple nodules,tumor thrombosis and high AFP level were risk factors that affect postoperative survival.Binhao Zhang Bixiang Zhang Zhiwei Zhang Zhiyong Huang Yifa Chen Minshan Chen Ping Bie Baogang Peng Liqun Wu Zhiming Wang Bo Li Jia Fan Lunxiu Qin Ping Chen Jingfeng Liu Zhe Tang Jun Niu Xinmin Yin Deyu Li Songqing He Bin Jiang Yilei Mao Weiping Zhou Xiaoping Chen 2018Science China(Life Sciences)2018,61,6:39
2Antioxidation Activities of Low-Molecular-Weight Gelatin Hydrolysate Isolated from the Sea Cucumber Stichopus japonicus显示文摘Gelatin extracted from the body wall of the sea cucumber (Stichopus japonicus) was hydrolyzed with flavourzyme.Low-molecular-weight gelatin hydrolysate (LMW-GH) of 700-1700 Da was produced using an ultrafiltration membrane bioreactor system.Chemiluminescence analysis revealed that LMW-GH scavenges high free radicals in a concentration-dependent manner;IC50 value for superoxide and hydroxyl radicals was 442 and 285 μg mL-1,respectively.LMW-GH exhibited excellent inhibitory characteristics against melanin synthesis and tyrosinase activity in B16 cells.Furthermore,LMW-GH notably increased intracellular glutathione (GSH),which in turn suppressed melanogenesis.LMW-GH performs antioxidation activity,holding the potential of being used as a valuable ingredient in function foods,cosmetics and pharmaceuticals or nutriceuticals.WANG Jingfeng WANG Yuming TANG Qingjuan WANG Yi CHANG Yaoguang ZHAO Qin XUE Changhu 2010Journal of Ocean University of China2010,9,1:13
3CAS9 is a genome mutator by directly disrupting DNA-PK dependent DNA repair pathway显示文摘With its high efficiency for site-specific genome editing and easy manipulation,the clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR associated protein 9(CAS9)system has become the most widely used gene editing technology in biomedical research.In addition,significant progress has been made for the clinical development of CRISPR/CAS9 based gene therapies of human diseases,several of which are entering clinical trials.Here we report that CAS9 protein can function as a genome mutator independent of any exogenous guide RNA(gRNA)in human cells,promoting genomic DNA double-stranded break(DSB)damage and genomic instability.CAS9 interacts with the KU86 subunit of the DNA-dependent protein kinase(DNA-PK)complex and disrupts the interaction between KU86 and its kinase subunit,leading to defective DNA-PK-dependent repair of DNA DSB damage via non-homologous end-joining(NHEJ)pathway.XCAS9 is a CAS9 variant with potentially higher fidelity and broader compatibility,and dCAS9 is a CAS9 variant without nuclease activity.We show that XCAS9 and dCAS9 also interact with KU86 and disrupt DNA DSB repair.Considering the critical roles of DNA-PK in maintaining genomic stability and the pleiotropic impact of DNA DSB damage responses on cellular proliferation and survival,our findings caution the interpretation of data involving CRISPR/CAS9-based gene editing and raise serious safety concerns of CRISPR/CAS9 system in clinical application.Shuxiang Xu Jinchul Kim Qingshuang Tang Qu Chen Jingfeng Liu Yang Xu Xuemei Fu 2020Protein & Cell2020,11,5:8
4An improved neural network model for prediction of mechanical properties of magnesium alloys显示文摘An improved neural network model was developed for prediction of mechanical properties in the de-sign and development of new types of magnesium alloys by refining the types of input variables and using a more reasonable algorithm. The results showed that the improved model apparently decreased the prediction errors, and raised the accuracy of the prediction results. Better preprocessing parame-ters were found to be [0.15, 0.90] for the tensile strength, [0.1, 0.9] for the yield strength, and [0.15, 0.90] for the elongation. When the above parameters were used, the relativity for predicition of strength was bigger than 0.95. By using improved ANN analysis, more reasonable process parameters and compo- sition could be obtained in some magnesium alloys without addition of strontoum.TANG AiTao LIU Bin PAN FuSheng ZHANG Jing PENG Jian WANG JingFeng 2009Science China(Technological Sciences)2009,52,1:5
5Chinese expert consensus on conversion therapy for hepatocellular carcinoma(2021 edition)显示文摘Recent advances in systemic and locoregional treatments for patients with unresectable or advanced hepatocellular carcinoma(HCC)have resulted in improved response rates.This has provided an opportunity for selected patients with initially unresectable HCC to achieve adequate tumor downstaging to undergo surgical resection,a‘conversion therapy’strategy.However,conversion therapy is a new approach to the treatment of HCC and its practice and treatment protocols are still being developed.Review the evidence for conversion therapy in HCC and develop consensus statements to guide clinical practice.Evidence review:Many research centers in China have accumulated significant experience implementing HCC conversion therapy.Preliminary findings and data have shown that conversion therapy represents an important strategy to maximize the survival of selected patients with intermediate stage to advanced HCC;however,there are still many urgent clinical and scientific challenges for this therapeutic strategy and its related fields.In order to summarize and learn from past experience and review current challenges,the Chinese Expert Consensus on Conversion Therapy for Hepatocellular Carcinoma(2021 Edition)was developed based on a review of preliminary experience and clinical data from Chinese and non-Chinese studies in this field and combined with recommendations for clinical practice.Sixteen consensus statements on the implementation of conversion therapy for HCC were developed.The statements generated in this review are based on a review of clinical evidence and real clinical experience and will help guide future progress in conversion therapy for patients with HCC.Hui-Chuan Sun Jian Zhou Zheng Wang Xiufeng Liu Qing Xie Weidong Jia Ming Zhao Xinyu Bi Gong Li Xueli Bai Yuan Ji Li Xu Xiao-Dong Zhu Dousheng Bai Yajin Chen Yongjun Chen Chaoliu Dai Rongping Guo Wenzhi Guo Chunyi Hao Tao Huang Zhiyong Huang Deyu Li Gang Li Tao Li Xiangcheng Li Guangming Li Xiao Liang Jingfeng Liu Fubao Liu Shichun Lu Zheng Lu Weifu Lv Yilei Mao Guoliang Shao Yinghong Shi Tianqiang Song Guang Tan Yunqiang Tang Kaishan Tao Chidan Wan Guangyi Wang Lu Wang Shunxiang Wang Tianfu Wen Baocai Xing Bangde Xiang Sheng Yan Dinghua Yang Guowen Yin Tao Yin Zhenyu Yin Zhengping Yu Bixiang Zhang Jialin Zhang Shuijun Zhang Ti Zhang Yamin Zhang Yubao Zhang Aibin Zhang Haitao Zhao Ledu Zhou Wu Zhang Zhenyu Zhu Shukui Qin Feng Shen Xiujun Cai Gaojun Teng Jianqiang Cai Minshan Chen Qiang Li Lianxin Liu Weilin Wang Tingbo Liang Jiahong Dong Xiaoping Chen Xuehao Wang Shusen Zheng Jia Fan 2022Hepatobiliary Surgery and Nutrition2022,11,2:4
6Industrial Structural Change and Economic Growth in China, 1987-2008显示文摘现在的纸从 1987 ~ 2008 在中国经济学习经济生长的来源和结构的变化的性质。用评估工业的贡献到经济生长的方法论,现在的纸证明 post-2000 subperiod 在中国经济作为生长的来源在服务性行业上标记增加的信赖。许多在真实 GDP 的加速或在在与 pre-2000 时期相比的 post-2000 subperiod 的中国的总数劳动生产率生长能被跟踪到增加的贡献从生产服务并且出口生产工业的高科技。证据显示中国经济向国内消费一直在重新平衡并且向生产工业的高科技转移它的出口部门。Jingfeng Zhao Jianmin Tang 2015China & World Economy2015,23,2:4
7A CRISPR/Cas12a-empowered surface plasmon resonance platform for rapid and specific diagnosis of the Omicron variant of SARS-CoV-2显示文摘The outbreak of the COVID-19 pandemic was partially due to the challenge of identifying asymptomatic and presymptomatic carriers of the virus,and thus highlights a strong motivation for diagnostics with high sensitivity that can be rapidly deployed.On the other hand,several concerning SARS-CoV-2 variants,including Omicron,are required to be identified as soon as the samples are identified as‘positive’.Unfortunately,a traditional PCR test does not allow their specific identification.Herein,for the first time,we have developed MOPCS(Methodologies of Photonic CRISPR Sensing),which combines an optical sensing technology-surface plasmon resonance(SPR)with the‘gene scissors’clustered regularly interspaced short palindromic repeat(CRISPR)technique to achieve both high sensitivity and specificity when it comes to measurement of viral variants.MOPCS is a low-cost,CRISPR/Cas12a-systemempowered SPR gene-detecting platform that can analyze viral RNA,without the need for amplification,within 38 min from sample input to results output,and achieve a limit of detection of 15 fM.MOPCS achieves a highly sensitive analysis of SARS-CoV-2,and mutations appear in variants B.1.617.2(Delta),B.1.1.529(Omicron)and BA.1(a subtype of Omicron).This platform was also used to analyze some recently collected patient samples from a local outbreak in China,identified by the Centers for Disease Control and Prevention.This innovative CRISPR-empowered SPR platform will further contribute to the fast,sensitive and accurate detection of target nucleic acid sequences with single-base mutations.Zhi Chen Jingfeng Li Tianzhong Li Taojian Fan Changle Meng Chaozhou Li Jianlong Kang Luxiao Chai Yabin Hao Yuxuan Tang Omar AAl-Hartomy Swelm Wageh Abdullah GAl-Sehemi Zhiguang Luo Jiangtian Yu Yonghong Shao Defa Li Shuai Feng William J.Liu Yaqing He Xiaopeng Ma Zhongjian Xie Han Zhang 2022National Science Review2022,9,8:3
8Evaluating urban expansion and land use change in Shijiazhuang, China, by using GIS and remote sensing显示文摘Jieying Xiao Yanjun Shen Jingfeng Ge Ryutaro Tateishi Changyuan Tang Yanqing Liang Zhiying Huang 2005Landscape and Urban Planning2005,,1:3
9CRISPR-Cas12a-Empowered Electrochemical Biosensor for Rapid and Ultrasensitive Detection of SARS-CoV-2 Delta Variant显示文摘Coronavirus disease 2019(COVID-19)is a highly contagious disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).The gold standard method for the diagnosis of SARS-CoV-2 depends on quantitative reverse transcription-polymerase chain reaction till now,which is time-consuming and requires expensive instrumentation,and the confirmation of variants relies on further sequencing techniques.Herein,we first proposed a robust technique-methodology of electrochemical CRISPR sensing with the advantages of rapid,highly sensitivity and specificity for the detection of SARS-CoV-2 variant.To enhance the sensing capability,gold electrodes are uniformly decorated with electro-deposited gold nanoparticles.Using DNA template identical to SARS-CoV-2 Delta spike gene sequence as model,our biosensor exhibits excellent analytical detection limit(50 fM)and high linearity(R2=0.987)over six orders of magnitude dynamic range from 100 fM to 10 nM without any nucleic-acid-amplification assays.The detection can be completed within 1 h with high stability and specificity which benefits from the CRISPR-Cas system.Furthermore,based on the wireless micro-electrochemical platform,the proposed biosensor reveals promising application ability in point-of-care testing.Chenshuo Wu Zhi Chen Chaozhou Li Yabin Hao Yuxuan Tang Yuxuan Yuan Luxiao Chai Taojian Fan Jiangtian Yu Xiaopeng Ma Omar AAl-Hartomy SWageh Abdullah GAl-Sehemi Zhiguang Luo Yaqing He Jingfeng Li Zhongjian Xie Han Zhang 2022Nano-Micro Letters2022,14,10:2
10Treatment of tibial plateau fractures with high strength injectable calcium sulphate显示文摘Baoqing Yu Kaiwei Han Hui Ma Chuncai Zhang Jiachan Su Jie Zhao Jingfeng Li Yushu Bai Hao Tang 2009International Orthopaedics2009,,:1
11miR-34 is associated with poor prognosis of patients with gallbladder cancer through regulating telomere length in tumor stem cells显示文摘Ke Jin Yonghua Xiang Jing Tang Guangchun Wu Junwei Li Huaichun Xiao Chunwang Li Yuxiang Chen Jingfeng Zhao 2014Tumor Biology2014,,2:1
12Rapid and simultaneous detection of Ureaplasma parvum and Chlamydia trachomatis antibodies based on visual protein microarray using gold nanoparticles and silver enhancement显示文摘Jingfeng Tang Zhenghui Xu Li Zhou Hong Qin Yefu Wang Hanhua Wang 2010Diagnostic Microbiology & Infectious Disease2010,,2:1
13Nitrogen contents of rice panicle and paddy by hyperspectral remote sensing 显示文摘Tang Yanlin Huang Jingfeng Cai Shaohong 2007Pakistan Journal of Biological Sciences2007,10,24:1
14Treatment of tibial plateau fractures with high strength injectable calcium sulphate显示文摘Baoqing Yu Kaiwei Han Hui Ma Chuncai Zhang Jiachan Su Jie Zhao Jingfeng Li Yushu Bai Hao Tang 2009International Orthopaedics2009,,4:1
15Identifying Qingkailing(清开灵)ingredients-dependent mesenchymal-epithelial transition factor-axiation“π”structuring module with angiogenesis and neurogenesis effects显示文摘OBJECTIVE:To explore the functional role of the drugdependent mesenchymal-epithelial transition(Met)-axiation'π'structural module of neurogenesis after processing by three components of Qingkailing injection in neurogenesis and angiogenesis in cerebral ischemia.METHODS:We used a Glutathione S-transferase(GST)-pull down assay,isothermal titration calorimetry assay,and other related methods to identify the relationships among Met,inositol polyphosphate phosphatase like 1(Inppl1),and death associated protein kinase 3(Dapk3)in this allosteric module.The biological effects of the modules of neurons generation composed of Met,Inppl1,and Dapk3 were measured through Western blot,apoptosis analysis,and double immunofluorescence labeling.RESULTS:The GST-pull down assay revealed that proline-serine-threonine rich domain of Met binds to the Src homology domain of Inppl1 to form a protein-protein complex;Dapk3 with a C-terminal domain interacts weakly with the protein kinase C domain of Met in the intracellular region.Thus,we obtained a“π”structuring module considered a neural regeneration module.The biological effects of angiogenesis and neurogenesis modules composed of Met,Inppl1,and Dapk3 were also verified.CONCLUSION:The study suggested that understanding the functional modules that contribute to pharmaceutics might provide novel signatures that can be used as endpoints to define disease processes under stroke or cerebral ischemia conditions.CHENG Kunming YUAN Jianan LIU Jun ZHANG Shengpeng XU Qixiang XIE Yong ZHAO Jingfeng ZHANG Xiaoxu TANG Xudong ZHENG Yongqiu WANG Zhong 2024Journal of Traditional Chinese Medicine2024,44,1:0
16B-lymphoid tyrosine kinase-mediated FAM83A phosphorylation elevates pancreatic tumorigenesis through interacting with β-catenin显示文摘Abnormal activation of Wnt/β-catenin-mediated transcription is closely associated with the malignancy of pancreatic cancer.Family with sequence similarity 83 member A(FAM83A)was shown recently to have oncogenic effects in a variety of cancer types,but the biological roles and molecular mechanisms of FAM83A in pancreatic cancer need further investigation.Here,we newly discovered that FAM83A binds directly toβ-catenin and inhibits the assembly of the cytoplasmic destruction complex thus inhibiting the subsequent phosphorylation and degradation.FAM83A is mainly phosphorylated by the SRC non-receptor kinase family member BLK(B-lymphoid tyrosine kinase)at tyrosine 138 residue within the DUF1669 domain that mediates the FAM83A-β-catenin interaction.Moreover,FAM83A tyrosine 138 phosphorylation enhances oncogenic Wnt/β-catenin-mediated transcription through promotingβ-catenin-TCF4 interaction and showed an elevated nucleus translocation,which inhibits the recruitment of histone deacetylases by TCF4.We also showed that FAM83A is a direct downstream target of Wnt/β-catenin signaling and correlates with the levels of Wnt target genes in human clinical pancreatic cancer tissues.Notably,the inhibitory peptides that target the FAM83A-β-catenin interaction significantly suppressed pancreatic cancer growth and metastasis in vitro and in vivo.Our results revealed that blocking the FAM83A cascade signaling defines a therapeutic target in human pancreatic cancer.Cefan Zhou Xiaoting Zhu Nanxi Liu Xueying Dong Xuewen Zhang Huili Huang Yu Tang Shicheng Liu Mengyu Hu Ming Wang Xiaoling Deng Shi Li Rui Zhang Yuan Huang Hao Lyu Shuai Xiao Sang Luo Declan William Ali Marek Michalak Xing-Zhen Chen Zhentian Wang Jingfeng Tang 2023Signal Transduction and Targeted Therapy2023,8,3:0
17Theoretical Investigation of Operation Modes of MHD Generators for Energy-bypass Engines显示文摘A MHD generator with different arrangements of electromagnetic fields will lead the generator working in three modes.A quasi-one-dimensional approximation is used for the model of the MHD generator to analyze the inner mechanism of operation modes.For the MHD generator with a uniform constant magnetic field,a specific critical electric field E_(cr) is required to decelerate a supersonic entrance flow into a subsonic exit flow.Otherwise,the generator works in a steady mode with a larger electric field than E_(cr) in which a steady supersonic flow is provided at the exit,or the generator works in a choked mode with a smaller electric field than E_(cr) in which the supersonic entrance flow is choked in the channel.The detailed flow field characteristics in different operation modes are discussed,demonstrating the relationship of operation modes with electromagnetic fields.Jingfeng Tang Nan Li Daren Yu 2014Journal of Thermal Science2014,23,6:0
18Effects of Dietary Protein Variations at Different Life-stages on Vocal Dominance of the African Clawed Frogs显示文摘How nutritional conditions during early development affect an organism’s phenotype at adulthood is still poorly understood despite a plethora of research on developmental plasticity.The'environmental matching'hypothesis predicts that individuals will have high fitness providing that their adult environment'matches'what they experienced during development.In contrast,the'silver spoon'hypothesis predicts that individuals who obtain better developmental resources will be generally superior.Here we tested these two hypotheses and examined the underlying hormonal mechanisms by manipulating the early dietary protein content of African clawed frogs(Xenopus laevis)for a year with a 2×2 factorial experimental design.We found that only a lowprotein food during development enhanced the vocal competition ability of male X.laevis,and that vocal dominance was associated with higher cortisol levels but not related with testosterone content.These results were not congruent with the'environmental matching'hypothesis or with the'silver spoon'hypothesis,suggesting the behavioral plasticity during development is more complex than our expectation in amphibians.Yan CAO Jiangyan SHEN Xiaocui WANG Song TAN Ping LI Jianghong RAN Yezhong TANG Jingfeng CHEN 2020Asian Herpetological Research2020,11,3:0
19Clinical characteristics of brain tumorrelated epilepsy and factors influencing the identification of epilepsy-associated tumors显示文摘Background:To analyze the clinical features of brain tumor-related epilepsy(BTRE)and explore the factors influencing the identification of epilepsy-associated tumor(EAT),in order to advance the clinical understanding of BTRE and EAT.Methods:Intracranial tumor origin and location as well as the type of epilepsy were retrospectively reviewed in 153 BTRE patients.The patients were further divided into the EAT and non-EAT groups,and comparisons were made for age,sex,tumor origin and location,and epilepsy type between the two groups.Results:The 153 BTRE patients were divided into 78 cases with primary intracranial tumor and 75 cases with tumor originating from extracranial metastasis,according to the origin of tumor.According to the location of tumor,116 cases had tumor lesions located in the brain parenchyma,and 37 cases had tumor lesions located in the meninges.Further,in the group with a brain parenchyma location,77 cases had single lobular involvement,and 39 cases had multiple-lobular involvement;84 cases had tumor lesions located in one hemisphere and 32 cases in both hemispheres.According to the type of epilepsy,92 cases had generalized seizures,and 61 cases had focal seizures.The type of epilepsy did not significantly correlate with the origin of intracranial tumor,the location of tumor lesions(in brain parenchyma or meninges)(P>0.05),or the hemispherical location(in one or two hemispheres)of lesions(P>0.05),but was significantly related with the lobular localization of lesions(P<0.05).The 153 cases of BTRE consisted of 87 EAT and 66 non-EAT,with significant differences in the origin,location and type(being glioma/non-glioma)of tumor.Logistic regression analysis showed that the type of tumor(i.e.whether being glioma)served as an independent factor for EAT identification;the lower the World Health Organization grade of glioma,the more likely the EAT is to be diagnosed(P<0.05).Conclusion:The majority of BTRE patients in this study had tumors located in the brain parenchyma.In addition,the patients with generalized seizures outnumbered those with focal seizures,and the type of epilepsy was correlated with the lobular location of tumor lesions.The EATs are mostly low-grade gliomas.Xianwen Zhang Liaoyuan Zheng Jingfeng Duan Zongping Li Yufeng Tang 2020Acta Epileptologica2020,2,1:0
20Epidemiological characteristics and clinical manifestations of pediatric patients with COVID-19 in China: A multicenter retrospective study显示文摘Importance:The Coronavirus disease 2019(COVID-19)global pandemic poses a considerable challenge for pediatricians.Objective:This study aimed to identify the epidemiological characteristics and clinical features of pediatric patients with COVID-19 in China.Methods:This multicenter retrospective study included pediatric patients from 46 hospitals in China,covering 12 provinces and two municipalities.Epidemiological,demographic,clinical,laboratory,treatment,and outcome data were analyzed.Results:In total,211 pediatric patients with COVID-19 were included in this study.The median age was 7.0 years(range:22 days to 18 years).Approximately 16.3%of the patients exhibited asymptomatic infections,23.0%had upper respiratory tract infections,and 60.7%had pneumonia,including two with severe pneumonia and one with critical illness.Approximately 78.7%of the pediatric patients occurred in familial clusters.The most three common symptoms or signs at onset in children with COVID-19 were fever(54.5%),cough(49.3%),and pharyngeal congestion(20.8%).Only 17.6%of the patients presented with decreased lymphocyte count,whereas 13.6%had increased lymphocyte count.Among the patients with pneumonia who exhibited abnormal chest computed tomography findings,18.2%(23/127)of the patients had no other symptoms.Generally,the chest radiographs showed abnormalities that affected both lungs(49.6%);ground-glass opacity(47.2%)was the most common manifestation.The cure and improvement rates were 86.7%(183/211)and 13.3%(28/211),respectively.Only one patient with an underlying condition received invasive mechanical ventilation;none of the patients died.Interpretation:Similar to adults,children of all age groups are susceptible to COVID-19.Fortunately,most pediatric patients have mild symptoms or remain asymptomatic,despite the high incidence of pneumonia.Decreased proportions of white blood cells and lymphocytes are less frequent in children than in adults.Yan Bai Liwei Gao Xianfeng Wang Lili Zhong Jingfeng Li Shenggang Ding Yuejie Zheng Jun Liu Yuxia Cui Lina Wang Mingfeng Han Jun Liu Xinping Jiang Min Jiang Junhua Li Ning Chen Yunxiao Shang Hourong Zhou Yi Xu Gen Lu Xing Chen Jizhi Xu Qihong Fan Yu Tang Jiang Wu Cen Li Xiaoxiang Yang Chunxi Chen Yonghong Yang Gary Wing-Kin Wong Adong Shen Tianyou Wang Runming Jin Baoping Xu Kunling Shen 2021Pediatric Investigation2021,5,3:0
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