Objective:To explore the clinical application value of pre-breathing mode in double-low imaging of 320-slices computed tomography(CT)for pulmonary artery.Methods:A total of 100 patients who underwent CT pulmonary angiography(CTPA)for suspected pulmonary embolism(PE)in Liuzhou People's Hospital from July 2021 to September 2022 were prospectively selected as the research subjects and they were randomly divided into observation group and control group,with 50 cases in each group.The patients of the control group adopted conventional breathing mode(the breathing password was activated after reaching the threshold,and the scan was triggered after 6 s),while the patients of the observation group adopted the pre-breathing mode(the breathing password was activated after 1 or 2 seconds,and the scan was triggered after reaching the threshold).Both two groups adopted double low-technique scan of 320 slices CT.The differences in delay time,radiation dose,the points of subjective and objective image quality,and other indicators were compared between the two groups.Results:The volume CT dose index(CTDIvol),dose length product(DLP),effective dose(ED)and delay time of the observation group were significantly lower than those of the control group(t=76.230,30.225,12.282,7.088,P<0.05),respectively.The comparison of the subjective points of image qualities between the two groups indicated that there were 25 cases with 5 points,23 cases with 4 points and 2 cases with 3 points in the observation group,and there were 21 cases with 5 points,26 cases with 4 points and 3 cases with 3 points in the control group.There was no significant difference in the averagely subjective points of image qualities between two groups(P>0.05).The signal-to-noise ratio(SNR)and signal to noise ratio(CNR)of the observation group were significantly lower than those of the control group,and the noise level(SD)of the observation group was significantly higher than that of the control group(t=25.441,23.886、11.426,P<0.05),respectively.The CT values of the artery trunk of right pulmonary,artery branch of right pulmonary,artery trunk of left pulmonary and artery branch of left pulmonary in the observation group were significantly higher than those in the control group(t=2.256,2.225,2.042,2.277,P<0.05),respectively.Conclusion:The pre-breathing mode can effectively improve CTPA image quality,and reduce radiation dose and the dosage of contrast agent,which clinical application effect is significant.It is worth learning.

BACKGROUND: Breast cancer patients who are positive for hormone receptor typically exhibit a favorable prognosis. It is controversial whether chemotherapy is necessary for them after surgery. Our study aimed to establish a multigene model to predict the relapse of hormone receptor-positive early-stage Chinese breast cancer after surgery and direct individualized application of chemotherapy in breast cancer patients after surgery. METHODS: In this study, differentially expressed genes (DEGs) were identified between relapse and nonrelapse breast cancer groups based on RNA sequencing. Gene set enrichment analysis (GSEA) was performed to identify potential relapse-relevant pathways. CIBERSORT and Microenvironment Cell Populations-counter algorithms were used to analyze immune infiltration. The least absolute shrinkage and selection operator (LASSO) regression, log-rank tests, and multiple Cox regression were performed to identify prognostic signatures. A predictive model was developed and validated based on Kaplan-Meier analysis, receiver operating characteristic curve (ROC). RESULTS: A total of 234 out of 487 patients were enrolled in this study, and 1588 DEGs were identified between the relapse and nonrelapse groups. GSEA results showed that immune-related pathways were enriched in the nonrelapse group, whereas cell cycle- and metabolism-relevant pathways were enriched in the relapse group. A predictive model was developed using three genes ( CKMT1B , SMR3B , and OR11M1P ) generated from the LASSO regression. The model stratified breast cancer patients into high- and low-risk subgroups with significantly different prognostic statuses, and our model was independent of other clinical factors. Time-dependent ROC showed high predictive performance of the model. CONCLUSIONS A multigene model was established from RNA-sequencing data to direct risk classification and predict relapse of hormone receptor-positive breast cancer in Chinese patients. Utilization of the model could provide individualized evaluation of chemotherapy after surgery for breast cancer patients.
Humans ; Female ; Breast Neoplasms/genetics* ; East Asian People ; Neoplasm Recurrence, Local/genetics* ; Breast ; Algorithms ; Chronic Disease ; Prognosis ; Tumor Microenvironment

The estimated new cases of breast cancer (BC) patients were 2.26 million in 2020, which accounted for 11.7% of all cancer patients, making it the most prevalent cancer worldwide. Early detection, diagnosis and treatment are crucial to reduce the mortality, and improve the prognosis of BC patients. Despite the widespread use of mammography screening as a tool for BC screening, the false positive, radiation, and overdiagnosis are still pressing issues that need to be addressed. Therefore, it is urgent to develop accessible, stable, and reliable biomarkers for non-invasive screening and diagnosis of BC. Recent studies indicated that the circulating tumor cell DNA (ctDNA), carcinoembryonic antigen (CEA), carbohydrate antigen 15-3 (CA15-3), extracellular vesicles (EV), circulating miRNAs and BRCA gene from blood, and the phospholipid, miRNAs, hypnone and hexadecane from urine, nipple aspirate fluid (NAF) and volatile organic compounds (VOCs) in exhaled gas were closely related to the early screening and diagnosis of BC. This review summarizes the advances of the above biomarkers in the early screening and diagnosis of BC.
Humans ; Female ; Biomarkers, Tumor ; Early Detection of Cancer ; Breast Neoplasms/diagnosis* ; Prognosis ; MicroRNAs/genetics*

OBJECTIVE To compare the efficacy ，safety and immunogenicity of bevacizumab biosimilars and original drugs for non-small cell lung cancer （NSCLC），and to provide evidence-based reference for clinical use. METHODS PubMed，Embase， Web of Science ，Cochrane Library ，CBM，CNKI，VIP，Wanfang database ，ClinicalTrials.gov，and Clinical Trial Center of China were searched from the establishment of the database to September 25，2021，randomized controlled trials （RCTs）about bevacizumab biosimilars（trial group ）versus bevacizumab original drugs （control group ）for NSCLC were collected. After literature screening ， data extraction and quality evaluation of included RCTs with bias risk assessment tool recommended by Cochrane Handbook 5.1.0， meta-analysis，sensitivity analysis and publication bias analysis were performed by using RevMan 5.3 software. RESULTS A total of 11 RCTs were included ，involving 6 596 patients in total. Meta-analysis showed that there was no statistical significance in the difference of overall response rate [RR＝0.97，95％CI（0.92，1.02），P＝0.22]，the total incidence of adverse reaction [RR＝1.00， 95％CI（0.99，1.01），P＝0.79]，the incidence of severe adverse reaction [RR＝1.04，95％CI（0.96，1.13），P＝0.38]，positive rate of anti-drug antibody [RR ＝1.10，95％CI（0.88，1.36，P＝0.41] and the incidence of common adverse reactions （except for vomiting）among 2 groups（P＞0.05）. The sensitivity analysis results showed that the obtained results were robust. The results of publication bias analysis showed that there was little possibility of publication bias. CONCLUSIONS The efficacy ，safety and immunogenicity of bevacizumab biosimilars used for NSCLC are equivalent to those of bevacizumab original drugs.

Objective:To explore the value of neutrophil to lymphocyte rate (NLR) combined with red blood cell distribution width to platelet count ratio (RPR) in evaluating the condition and prognosis of emergency elderly sepsis patients.Methods:A prospective research method was conducted to select 169 elderly patients with sepsis who visited the emergency department of Xuanwu Hospital of Capital Medical University from January 2020 to February 2022.After admission, blood routine examination, chest computerized tomography, biochemical examination, procalcitonin, and pathogenic examination were given, and the scores of acute physiology and chronic health evaluation (APACHE Ⅱ) were scored according to worst value of 24 hours. After 28 days of follow-up, the patients were divided into the survival group(125 cases) and the death group(44 cases) according to the prognosis. The differences of white blood cell count(WBC), NLR, PCT, RPR and APACHE Ⅱ scores were compared between the two groups. The correlation between NLR,RPR and APACHE Ⅱ scores were analyzed. The difference of area under receiver operating characteristic curve (ROC) of RPR, NLR, their combination and PCT in predicting mortality were compared in elderly patients with sepsis. The independent sample t test was used to compare the measurement data with normal distribution, and the χ 2 test was used to compare the enumeration data. The risk factors were analyzed by multiple logistic regression analysis. Results:There was no significant difference in WBC between the survival group and the death group ( P=0.361). The APACHE Ⅱ scores ((18.52±2.41) points), RPR (0.17±0.03), NLR (10.64±3.48), PCT ((2.55±1.14) μg/L) in the death group were higher than those in the survival group ((14.17±2.71) points, (0.14±0.03), NLR (7.67±3.33), (1.19±0.81) μg/L), the difference was statistically significant ( t values were 9.44,7.32,4.92, and 7.32, respectively; all P<0.001). RPR and NLR were positively correlated with APACHE Ⅱ scores ( r=0.393,0.368;both P<0.001). Multivariate logistic regression analysis showed that increased NLR ( OR=1.174,95% CI 1.041-1.325), procalcitonin ( OR=4.353,95% CI 2.382-7.954), RPR ( OR=14.247,95% CI 2.635-77.025) were independent risk factors for the prognosis of sepsis patients ( P values were 0.009,<0.001, and 0.002, respectively).The area under receiver operating characteristic curve (AUC) of PCT in predicting mortality was 0.859 (95% CI:0.801-0.917), the AUC of RPR was 0.755 (95% CI:0.665-0.845), and the AUC of NLR was 0.727 (95% CI: 0.643-0.812). The AUC of RPR and NLR was smaller than that of PCT ( P=0.033, 0.015), but the AUC of RPR combined with NLR was 0.799, which had no significant difference compared with PCT ( P=0.195). Conclusion:Both NLR and RPR had a certain predictive value for the condition and prognosis of elderly sepsis patients in emergency, and their combined evaluation value was similar to that of PCT.

Primary liver cancer (PLC) is an aggressive tumor and prone to metastasize and recur. According to pathological features, PLC are mainly categorized into hepatocellular carcinoma, intrahepatic cholangiocarcinoma, mixed hepatocellular cholangiocarcinoma, and fibrolamelic hepatocellular carcinoma, etc. At present, surgical resection, radiotherapy and chemotherapy are still the main treatments for PLC, but the specificities are poor and the clinical effects are limited with a 5-year overall survival rate of 18%. Liver cancer stem cells (LCSCs) are a specific cell subset existing in liver cancer tissues. They harbor the capabilities of self-renewal and strong tumorigenicity, driving tumor initiation, metastasis, drug resistance and recurrence of PLC. Therefore, the identification of molecular markers and the illustration of mechanisms for stemness maintenance of LCSCs can not only reveal the molecular mechanisms of PLC tumorigenesis, but also lay a theoretical foundation for the molecular classification, prognosis evaluation and targeted therapy of PLC. The latest research showed that the combination of 5-fluorouracil and CD13 inhibitors could inhibit the proliferation of CD13+ LCSCs, thereby reducing overall tumor burden. Taken together, LCSCs could be the promising therapeutic targets of PLC in the future. This review summarizes the latest progress in molecular markers, mechanisms for stemness maintenance and targeted therapies of LCSCs.
Carcinoma, Hepatocellular/genetics* ; Humans ; Liver Neoplasms/genetics* ; Neoplastic Stem Cells ; Prognosis

To enhance recombinant protein production by CHO cells, We compared the impact of overexpression of metabolic enzymes, namely pyruvate carboxylase 2 (PYC2), malate dehydrogenase Ⅱ (MDH2), alanine aminotransferase Ⅰ (ALT1), ornithine transcarbamylase (OTC), carbamoyl phosphate synthetase Ⅰ (CPSⅠ), and metabolism related proteins, namely taurine transporter (TAUT) and Vitreoscilla hemoglobin (VHb), on transient expression of anti-hLAG3 by ExpiCHO-S. Overexpression of these 7 proteins could differentially enhance antibody production. OTC, CPSI, MDH2, and PYC2 overexpression could improve antibody titer by 29.2%, 27.6%, 24.1%, and 20.3%, respectively. Specifically, OTC and MDH2 could obviously improve early-stage antibody production rate and the culture period was shortened by 4 days compared with that of the control. In addition, OTC and MDH2 had little impact on the affinity of anti-hLAG3. In most cases, overexpression of these proteins had little impact on the cell growth of ExpiCHO-S. MDH2 and ALT1 overexpression in H293T cells could also improve antibody production. Overall, overexpression of enzymes involved in cellular metabolism is an effective tool to improve antibody production in transient expression system.
Animals ; CHO Cells ; Cricetinae ; Cricetulus ; Enzymes/metabolism* ; Recombinant Proteins/genetics*

Bispecific antibody (BsAb) has two different antigen-binding sites, divided into the "IgG-like" format and the "non-IgG-like" format. Different formats have different characteristics and applications. BsAb has higher sensitivity and specificity than conventional antibodies, with special functions such as recruitment of immune cells and blocking of dual signaling pathways, playing an important role in immune-diagnosis and therapy. With the deterioration of the global environment and the irregular living habits of people, the incidence of tumor is becoming higher and higher. Tumor becomes the most serious fatal disease threatening human health after cardiovascular disease. There are 12 million estimated new tumor cases each year worldwide. The major clinical treatments of tumor are surgical resection, chemoradiotherapy, target therapy. Tumor immunotherapy is a novel approach for tumor treatment in recent years, and activates human immune system to control and kill tumor cells. Although the traditional monoclonal antibodies have already acquired some therapeutic effects in tumor targeted therapy and immunotherapy, they induce drug resistance resulted from the heterogeneity and plasticity of tumors. Binding to two target antigens at the same time, BsAb has been used in the clinical treatment of tumors and obtained promising outcomes. This review elaborates the research progress and applications of bispecific antibody in clinical tumor therapy.
Antibodies, Bispecific/therapeutic use* ; Antibodies, Monoclonal/therapeutic use* ; Humans ; Immunotherapy ; Neoplasms/therapy*

Genome editing is a genetic manipulation technique that can modify DNA sequences at the genome level, including insertion, knockout, replacement and point mutation of specific DNA fragments. The ultimate principle of genome editing technology relying on engineered nucleases is to generate double-stranded DNA breaks at specific locations in genome and then repair them through non-homologous end joining or homologous recombination. With the intensive study of these nucleases, genome editing technology develops rapidly. The most used nucleases include meganucleases, zinc finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindromic repeats associated Cas proteins. Based on introducing the development and principles of above mentioned genome editing technologies, we review the research progress of CRISPR/Cas9 system in the application fields of identification of gene function, establishment of disease model, gene therapy, immunotherapy and its prospect.
CRISPR-Cas Systems/genetics* ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics* ; Gene Editing ; Technology ; Transcription Activator-Like Effector Nucleases/metabolism*

Three-dimensional (3D) genomics is an emerging discipline that studies the 3D spatial structure and function of genomes, focusing on the 3D spatial conformation of genome sequences in the nucleus and its biological effects on biological processes such as DNA replication, DNA recombination and gene expression regulation. The invention of chromosome conformation capture (3C) technology speeds up the research on 3D genomics and its related fields. Furthermore, the development of 3C-based technologies, such as the genome-wide chromosome conformation capture (Hi-C) and chromatin interaction analysis using paired-end tag sequencing (ChIA-PET), help scientists get insight into the 3D genomes of various species. Aims of 3D genomics are to reveal the spatial genome organization, chromosomal interaction patterns, mechanisms underlying the transcriptional regulation and formation of biological traits of microorganism, plant, animal. Additionally, the identification of key genes and signaling pathways associated with biological processes and disease via chromosome 3C technology boosts the rapid development of agricultural science, life science and medical science. This paper reviews the research progress of 3D genomics, mainly in the concept of 3D genomics, the development of chromosome 3C technologies and their applications in agricultural science, life science and medical science, specifically in the field of tumor.
Animals ; Cell Nucleus ; Chromatin/genetics* ; Chromosomes/genetics* ; Genome ; Genomics