1.Prospective multicenter cohort study on breast cancer screening using an automated breast ultrasound with remote reading
Xiaozhi DANG ; Yi GAO ; Xiang GU ; Yan JU ; Dongsheng YI ; Huan LIN ; Yi REN ; Xiaojie YUAN ; Hongping SONG
Chinese Journal of Oncology 2024;46(11):1067-1075
Objective:To construct a remote screening network for breast cancer based on automated breast ultrasound (ABUS) and explore the value of ABUS with remote reading for breast cancer screening.Methods:We constructed a remote breast cancer screening network including one remote reading center and 48 image-acquisition centers. We recruited women to participate in breast cancer screening at one of these image-acquisition centers from January 2021 to January 2023. The technicians collected the whole breast images using the ABUS. The images were then sent to the reading center through the PVBUS System and interpreted independently by two radiologists using the Breast Imaging Reporting and Data System (BI-RADS). BI-RADS categories 1 and 2 indicate negative screening results, and women diagnosed with these categories were recommended for annual breast ultrasound screening. BI-RADS categories 3, 4, and 5 indicate positive results. Women with BI-RADS category 3 lesions were recommended for follow-up examinations every 6 months using ABUS or handheld ultrasound, while those with BI-RADS 4 and 5 lesions were suggested to undergo pathological examinations.Results:In our study, we enrolled 10 344 women who completed the ABUS screening and were followed up for more than 12 months. After remote reading, 6 164 women were diagnosed with BI-RADS category 1 and 2 626 woman were within BI-RADS category 2. In contrast, 1 404 women were within BI-RADS category 3, a total of 135 women were within BI-RADS category 4, and 15 women were within BI-RADS category 5. The positive screening rate of ABUS was 15.0% (1 554/10 344). The ABUS with remote reading had a detection rate of 3.7/1 000 (38/10 344) for breast cancer screening, with a sensitivity of 97.4% (38/39) and a specificity of 85.3% (8 789/10 305). Among the 38 breast cancer cases detected, 92.1% (35/38) were invasive carcinomas, and 63.2% (24/38) were stage 0 or Ⅰ breast cancers.Conclusions:Breast cancer screening based on ABUS with remote reading provided an efficient and feasible solution to the problem of unevenly distributed medical resources and medical staff levels in various regions of China, enabling the decentralization of high-quality medical resources and improving the accessibility of high-quality screening services. It has provided an alternative for breast cancer screening in China.
2.To construct a risk model and study the immune mechanism of genes related to myocardial infarction and cuproptosis based on bioinformatics and single cell sequencing
Xing JU ; Lianqun JIA ; Zhe ZHANG ; Dongsheng WEI ; Jingsheng ZHANG ; Guanlin YANG
Chinese Journal of Immunology 2024;40(11):2247-2256
Objective:Integrating genes and GEO database related cuproptosis chips,to analyze connection between cupropto-sis genes,immune infiltration and myocardial infarction(MI),construct risk prediction model,predict Western medicine and Chi-nese medicine,analyze miRNA-mRNA regulatory network,and to provides a new research direction for the future study of MI-related cuproptosis mechanism and immune infiltration.Methods:By GEO database retrieval of MI related chips,standardized processing and MI-related cuproptosis genes screening were performed,and immunoinfiltration analysis and quantification were performed based on the treated gene expression matrix,correlation between immune infiltrating cells and function was analyzed,as well as their differ-ences in MI group and the control group.Cuproptosis genes that most related to MI in immune infiltration were screened out,and the risk model was constructed to analyze the risk probability of cuproptosis genes in MI.The Enrichr website and Coremine Medical data-base were used to predict cuproptosis-related genes in MI in Western medicine and traditional Chinese medicine.Finally,the up-stream mirnas of FDX1 and SLC31A1 were predicted by miRTarBase,Starbase and Targetscan databases,and miRNA-mRNA regula-tory networks were constructed.Results:Correlation of immune infiltration showed that Tfh cells and B cells had the strongest positive correlation(r=0.68),while regulatory T cells and iDC had the strongest negative correlation(r=-0.63);the difference analysis of im-mune infiltration showed that the differences among mast cells,NK cells and Th1 cells in the MI group at the cellular level were the most significant(P<0.001);and the differences in APC co-inhibition and MHCⅠ at the functional level were the most significant(P<0.001).Six genes with the highest correlation between immune cells and immune function were screened out:ATP7A,DLD,FDX1,LIAS,LIPT1 and SLC31A1.Results of the risk model showed that the high levels of FDX1 and SLC31A1 were negatively correlated with the risk prediction of MI.A total of 21 Western medicines and 30 traditional medicines were predicted by database comparison.miRTarBase,Starbase and Targetscan databases predicted 9 upstream miRNAs of cuproptosis-related genes in MI,including has-miR-122-5p.Conclusion:Tfh cells,B cells,para-inflammatory,typeⅠinterferon response and other related immune cells and functions may play important roles in pathogenesis and prognosis of MI.FDX1 and SLC31A1 as the key genes of cuproptosis process,are negatively correlated with MI.A total of 30 kinds of traditional Chinese medicines including Spirulina,sheep liver,Wen ezhu,Pian jianghuang and Yujin may have potential value in treatment of MI.Finally,9 miRNAs including has-miR-122-5p may play an important role in the regulation of cuproptosis in myocardial infarction.
3.Prospective multicenter cohort study on breast cancer screening using an automated breast ultrasound with remote reading
Xiaozhi DANG ; Yi GAO ; Xiang GU ; Yan JU ; Dongsheng YI ; Huan LIN ; Yi REN ; Xiaojie YUAN ; Hongping SONG
Chinese Journal of Oncology 2024;46(11):1067-1075
Objective:To construct a remote screening network for breast cancer based on automated breast ultrasound (ABUS) and explore the value of ABUS with remote reading for breast cancer screening.Methods:We constructed a remote breast cancer screening network including one remote reading center and 48 image-acquisition centers. We recruited women to participate in breast cancer screening at one of these image-acquisition centers from January 2021 to January 2023. The technicians collected the whole breast images using the ABUS. The images were then sent to the reading center through the PVBUS System and interpreted independently by two radiologists using the Breast Imaging Reporting and Data System (BI-RADS). BI-RADS categories 1 and 2 indicate negative screening results, and women diagnosed with these categories were recommended for annual breast ultrasound screening. BI-RADS categories 3, 4, and 5 indicate positive results. Women with BI-RADS category 3 lesions were recommended for follow-up examinations every 6 months using ABUS or handheld ultrasound, while those with BI-RADS 4 and 5 lesions were suggested to undergo pathological examinations.Results:In our study, we enrolled 10 344 women who completed the ABUS screening and were followed up for more than 12 months. After remote reading, 6 164 women were diagnosed with BI-RADS category 1 and 2 626 woman were within BI-RADS category 2. In contrast, 1 404 women were within BI-RADS category 3, a total of 135 women were within BI-RADS category 4, and 15 women were within BI-RADS category 5. The positive screening rate of ABUS was 15.0% (1 554/10 344). The ABUS with remote reading had a detection rate of 3.7/1 000 (38/10 344) for breast cancer screening, with a sensitivity of 97.4% (38/39) and a specificity of 85.3% (8 789/10 305). Among the 38 breast cancer cases detected, 92.1% (35/38) were invasive carcinomas, and 63.2% (24/38) were stage 0 or Ⅰ breast cancers.Conclusions:Breast cancer screening based on ABUS with remote reading provided an efficient and feasible solution to the problem of unevenly distributed medical resources and medical staff levels in various regions of China, enabling the decentralization of high-quality medical resources and improving the accessibility of high-quality screening services. It has provided an alternative for breast cancer screening in China.
4.Life History Recorded in the Vagino-cervical Microbiome Along with Multi-omes
Jie ZHUYE ; Chen CHEN ; Hao LILAN ; Li FEI ; Song LIJU ; Zhang XIAOWEI ; Zhu JIE ; Tian LIU ; Tong XIN ; Cai KAIYE ; Zhang ZHE ; Ju YANMEI ; Yu XINLEI ; Li YING ; Zhou HONGCHENG ; Lu HAORONG ; Qiu XUEMEI ; Li QIANG ; Liao YUNLI ; Zhou DONGSHENG ; Lian HENG ; Zuo YONG ; Chen XIAOMIN ; Rao WEIQIAO ; Ren YAN ; Wang YUAN ; Zi JIN ; Wang RONG ; Liu NA ; Wu JINGHUA ; Zhang WEI ; Liu XIAO ; Zong YANG ; Liu WEIBIN ; Xiao LIANG ; Hou YONG ; Xu XUN ; Yang HUANMING ; Wang JIAN ; Kristiansen KARSTEN ; Jia HUIJUE
Genomics, Proteomics & Bioinformatics 2022;20(2):304-321
The vagina contains at least a billion microbial cells,dominated by lactobacilli.Here we perform metagenomic shotgun sequencing on cervical and fecal samples from a cohort of 516 Chinese women of reproductive age,as well as cervical,fecal,and salivary samples from a second cohort of 632 women.Factors such as pregnancy history,delivery history,cesarean section,and breastfeeding were all more important than menstrual cycle in shaping the microbiome,and such information would be necessary before trying to interpret differences between vagino-cervical micro-biome data.Greater proportion of Bifidobacterium breve was seen with older age at sexual debut.The relative abundance of lactobacilli especially Lactobacillus crispatus was negatively associated with pregnancy history.Potential markers for lack of menstrual regularity,heavy flow,dysmenor-rhea,and contraceptives were also identified.Lactobacilli were rare during breastfeeding or post-menopause.Other features such as mood fluctuations and facial speckles could potentially be predicted from the vagino-cervical microbiome.Gut and salivary microbiomes,plasma vitamins,metals,amino acids,and hormones showed associations with the vagino-cervical microbiome.Our results offer an unprecedented glimpse into the microbiota of the female reproductive tract and call for international collaborations to better understand its long-term health impact other than in the settings of infection or pre-term birth.
5.Precision Methylome and In Vivo Methylation Kinetics Characterization of Klebsiella pneumoniae
Fu JING ; Zhang JU ; Yang LI ; Ding NAN ; Yue LIYA ; Zhang XIANGLI ; Lu DANDAN ; Jia XINMIAO ; Li CUIDAN ; Guo CHONGYE ; Yin ZHE ; Jiang XIAOYUAN ; Zhao YONGLIANG ; Chen FEI ; Zhou DONGSHENG
Genomics, Proteomics & Bioinformatics 2022;20(2):418-434
Klebsiella pneumoniae(K.pneumoniae)is an important pathogen that can cause severe hospital-and community-acquired infections.To systematically investigate its methylation features,we determined the whole-genome sequences of 14 K.pneumoniae strains covering varying serotypes,multilocus sequence types,clonal groups,viscosity/virulence,and drug resistance.Their methy-lomes were further characterized using Pacific Biosciences single-molecule real-time and bisulfite technologies.We identified 15 methylation motifs[13 N6-methyladenine(6mA)and two 5-methylcytosine(5mC)motifs],among which eight were novel.Their corresponding DNA methyl-transferases were also validated.Additionally,we analyzed the genomic distribution of GATC and CCWGG methylation motifs shared by all strains,and identified differential distribution pat-terns of some hemi-/un-methylated GATC motifs,which tend to be located within intergenic regions(IGRs).Specifically,we characterized the in vivo methylation kinetics at single-base resolu-tion on a genome-wide scale by simulating the dynamic processes of replication-mediated passive demethylation and MTase-catalyzed re-methylation.The slow methylation of the GATC motifs in the replication origin(oriC)regions and IGRs implicates the epigenetic regulation of replication initiation and transcription.Our findings illustrate the first comprehensive dynamic methylome map of K.pneumoniae at single-base resolution,and provide a useful reference to better understand epigenetic regulation in this and other bacterial species.
6.Genomic Epidemiology of Carbapenemase-producing Klebsiella pneumoniae in China
Li CUIDAN ; Jiang XIAOYUAN ; Yang TINGTING ; Ju YINGJIAO ; Yin ZHE ; Yue LIYA ; Ma GUANNAN ; Wang XUEBING ; Jing YING ; Luo XINHUA ; Li SHUANGSHUANG ; Yang XUE ; Chen FEI ; Zhou DONGSHENG
Genomics, Proteomics & Bioinformatics 2022;(6):1154-1167
The rapid spread of carbapenemase-producing Klebsiella pneumoniae(cpKP)poses seri-ous threats to public health;however,the underlying genetic basis for its dissemination is still unknown.We conducted a comprehensive genomic epidemiology analysis on 420 cpKP isolates col-lected from 70 hospitals in 24 provinces/autonomous regions/municipalities of China during 2009-2017 by short-/long-read sequencing.The results showed that most cpKP isolates were categorized into clonal group 258(CG258),in which ST11 was the dominant clone.Phylogenetic analysis revealed three major clades including the top one of Clade 3 for CG258 cpKP isolates.Additionally,carbapenemase gene analysis indicated that blaKPC was dominant in the cpKP isolates,and most blaKPC genes were located in five major incompatibility(Inc)groups of blaKPC-harboring plasmids.Importantly,three advantageous combinations of host-blaKPC-carrying plasmid(Clade 3.1+3.2-IncFⅡpHN7A8,Clade 3.1+3.2-IncFⅡpHN7A8:IncR,and Clade 3.3-IncFⅡpHN7A8:InCpA1763-KPC)were identified to confer cpKP isolates the advantages in both genotypes(strong correlation/coevolution)and phenotypes(resistance/growth/competition)to facilitate the nationwide spread of ST11/CG258 cpKP.Intriguingly,Bayesian skyline analysis illustrated that the three advanta-geous combinations might be directly associated with the strong population expansion during 2007-2008 and subsequent maintenance of the population of ST11/CG258 cpKP after 2008.We then examined drug resistance profiles of these cpKP isolates and proposed combination treatment regimens for CG258/non-CG258 cpKP infections.Thus,the findings of our systematical analysis shed light on the molecular epidemiology and genetic basis for the dissemination of ST11/CG258 cpKP in China,and much emphasis should be given to the close monitoring of advantageous cpKP-plasmid combinations.
7.Study of prognosis and influencing factors of circulatory infarction after intravascular intervention
Ying JIN ; Chunying LI ; Dongsheng JU
Journal of Apoplexy and Nervous Diseases 2020;37(11):1027-1030
Objective To investigate the prognosis and influencing factors of intravascular interventional therapy for posterior circulation infarction. Method For selecting our department admitted in October 2019 and October 2017-two years hospitalized with a total of 42 cases of clinically diagnosed patients with posterior circulation infarction,patient gender,age,on admission,the main symptoms and signs,pathogenic factors,pathogenesis time interval,when to see a doctor to vascular disease opening time,lesion blood vessel parts,collateral compensatory,operation method choice and recanalization,vascular interventional treatment and postoperative 7 days before the NIHSS score,GCS score,mRS score when discharged from hospital,postoperative complications and prognosis of 90 days. According to the improved Rankin score of patients with 90-day prognosis,the patients were divided into a good prognosis group (mRS score <4 points) and a poor prognosis group (mRS score ≥ 4 points),and statistical analysis was conducted. Results (1) For posterior circulation infarction,multiple interventional therapies were used to treat the lesion vessel opening rate of 71.4%,the 3-month mortality rate of posterior circulation infarction was 28.6%. And the good prognosis rate was 50%. (2)Univariate analysis suggested a statistically significant difference in the prognosis of patients with smoking P<0.01). (3)Logistic regression analysis showed that after adjusting for cerebrovascular risk factors such as smoking,lower basilar artery occlusion was associated with poor prognosis. (4)Good intraoperative lesion vessels (Ⅱb level or Ⅲ level) and is related to good prognosis. Conclusion Endovascular interventional therapy is an efficient and rapid method for posterior circulation infarction to open blood vessels. Good recanalization of diseased blood vessels during operation is positively correlated with good prognosis,while smoking and lower basilar artery occlusion are correlated with poor prognosis.
8.Relationship between chronic diarrhea with normal colonoscopy findings and terminal ileum lesions.
Hongling LI ; Changcheng WANG ; Shuqing LIU ; Dongsheng XU ; Ju ZHANG ; Hongmei CHEN
Chinese Medical Journal 2014;127(16):2915-2917
BACKGROUNDThe causes and mechanisms of chronic diarrhea are complex. This study aimed to explore the relationship between chronic diarrhea with normal colonoscopy findings and terminal ileum lesions.
METHODSAll cases were collected from January 2009 to June 2010. The 40 patients in the patient group had chronic diarrhea with normal colonoscopy findings. Those who had hyperthyroidism, diabetes, chronic pancreatitis, cirrhosis, atrophic gastritis, short bowel syndrome and connective tissue diseases had been excluded. The control group contained 40 healthy individuals without diarrhea. Endoscopy of the terminal ileum was applied in both groups, with the endoscope inserted into terminal ileum for more than 20 cm. The patients diagnosed of chronic diarrhea with terminal ileum lesions were treated with metronidazole and probiotics for 10-14 days.
RESULTSBefore treatment there were significant differences in endoscopy findings of the terminal ileum between the two groups (P < 0.05). In the patient group, endoscopy showed congestion, edema, erosion and ulcers in 29 cases, hyperplasia and enlargement of lymphoid follicles in 10 cases with a maximal diameter of 7-8 mm, and 1 case showed normal endoscopy results. After treatment, 35 patients recovered from diarrhea, and terminal ileum lesions disappeared in 30 cases as determined by endoscopy. In the control group, endoscopy showed scattered hyperplasia of lymphoid follicles in 5 cases, and the follicles were small with the maximal diameter being 3 mm. There was no hyperemia, edema, erosion or ulcers.
CONCLUSIONSChronic diarrhea patients with normal colonoscopy findings may have lesions in the terminal ileum that can be detected by endoscopy; including hyperemia, erosion, ulcers and lymphoid follicle hyperplasia. Therapeutic effect is good with metronidazole and probiotics.
Adult ; Chronic Disease ; Colonoscopy ; Diarrhea ; diagnosis ; drug therapy ; Female ; Humans ; Ileum ; pathology ; Male ; Metronidazole ; therapeutic use ; Middle Aged ; Probiotics ; therapeutic use ; Young Adult
9.Biocompatibility of magnetic chitosan microspheres
Ziyu WANG ; Ju DONG ; Dongsheng ZHANG
Chinese Journal of Tissue Engineering Research 2013;(42):7414-7419
BACKGROUND:Chitosan modification for magnetic iron oxide nanoparticles can improve the agglomeration and stability of magnetic iron oxide nanoparticles, and in addition, it can be used for tumor hyperthermia and gene therapy in the future.
OBJECTIVE:To explore the biocompatibility of magnetic chitosan microspheres which have the potential application in tumor hyperthermia and gene therapy.
METHODS:Magnetic iron oxide nanoparticles were prepared using the modified chemical precipitation. Phacoemulsification method was used to add chitosan into magnetic iron oxide nanoparticles in the preparation of magnetic chitosan microspheres. Then, the fol owing tests were performed. (1) Cytotoxicity test:L-929 cells were cultured in 1640 medium, polyacrylamide monomer solution, 100%, 75%, 50%, 25%of magnetic chitosan microsphere extracts. (2) Hemolysis test:Magnetic chitosan microspheres leaching solution, saline and distil ed water were added. (3) Micronucleus test:Kunming mice were intraperitoneal y injected with magnetic chitosan microspheres suspension containing 5, 3.75, 2.5, 1.25 g/kg iron oxide magnetic fluid, cyclophosphamide and saline, respectively.
RESULTS AND CONCLUSION:Magnetic chitosan microspheres of 200-300 nm in diameter had an increased dispersion effect. The result of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that the toxicity of the material on L-929 celllines belonged to no cytotoxicity. In the hemolysis test, the hemolysis rate of magnetic chitosan microspheres was 0.69%far less than 5%. In the micronucleus test, magnetic chitosan microspheres suspension did not cause DNA fragmentation and aneuploidy, and did not result in genetic toxicological effects produced by micronuclei. The magnetic chitosan microspheres did not appear with cacogenesis and mutagenesis. From the results, magnetic chitosan microspheres are a kind of high biocompatibility material.
10.An easy and effective way to produce experimental oxygen-glucose deprivation in cultured neurons
Min DENG ; Xiaodong JU ; Nan ZHANG ; Yun ZHANG ; Lu TANG ; Dongsheng FAN
Chinese Journal of Tissue Engineering Research 2009;13(7):1393-1396
BACKGROUND: Oxygen-glucose depdvation (OGD) in cultured neurons simulates stroke to a certain degree and plays an important role in studying processing and pathophysiological mechanism of ischemic neuronal injury.OBJECTIVE: To produce experimental OGD models in cultured neurons.DESIGN, TIME AND SETTING: A grouping controlled study was performed at the Center Laboratory of Third Hospital, Peking University from January 2007 to March 2008.MATERIALS: Fetal Wistar rats with gestational age of 17-19 days were collected in this study.METHODS: Primary cultures of cortical neurons that were derived from fetal Wistar rats with gestational age of 17-19 days were performed to remove pollutional non-neuronal cells. OGD was produced by incubation with non-glucose balanced salt solution and 2% Oxyrasa in 7-day cultured cortical neuron cultures. Cell cultures were kept in a humidified 37 ℃ incubator. In the control group, cell culture medium was replaced with balanced salt solution containing 20 mmol/L glucose. In the sham operation group,balanced salt solution containing 20 mmol/L glucose and Oxyrasawere used to replace the medium.MAIN OUTCOME MEASURES: Oxygen concentration in the culture medium was measured with blood gas analysis; neuronal death in the experimental group was observed under phase contrast microscope; lactate dehydrogenase activity was detected with lactate dehydrogenasa assay; effect of oxygen-glucose deprivation on neuronal viability was observed with trypan blue staining.RESULTS: Measurement of oxygen concentration showed that hypoxia could be quickly achieved shortly after the addition of Oxyrase; lactate dehydrogenase assay revealed that after treatments of neuron cultures with Oxyrase and non-glucose balanced salt solution, lactate dehydrogenase release increased significantly with the treatment time; trypan blue staining and phase contrast microscope showed that cell viability decreased after treatments of Oxyrase and non-glucose balanced salt solution, and most neurons died 6 hours after OGD.CONCLUSION: These results show that Oxyrase, together with non-glucose balanced salt solution, can be conveniently used to produce OGD condition in cultured neuronal cells which is greatly useful in the study of simulating cerebral ischemia in vitro.


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