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*

The "new engineering" concept requires that in addition to laying a solid professional foundation, engineering colleges and universities in China should also pay attention to improving the humanistic quality and developing a professional ethics education in training the engineering and technical talents. One important way is to carry out the engineering ethics education. By referring to the mature case-teaching ideas around the world and combining the practical experience accumulated in recent years, this paper focuses on the curriculum development and teaching reform of engineering ethics for students studying biological and medical engineering, from the perspectives of case selection and teaching method innovation. It also introduces some typical case studies, and summarizes the teaching effect analyzed from questionnaire.
Humans ; Curriculum ; Engineering/education* ; Students ; Ethics, Professional ; Biology/education*

Cadmium (Cd) is a common heavy metal in the environment. Cd²⁺ may penetrate the blood-brain barrier and produce neurotoxicity, thus inducing various neurodegenerative diseases. Celastrol is an effective component of Tripterygium wilfordii Hook. F., which has many pharmacological effects such as anti-cancer and anti-inflammatory. Here we explored the effect of celastrol on the corresponding neurotoxicity induced by Cd²⁺. Cell proliferation test, cell membrane integrity test, and cell morphology were observed to analyze the effect of Cd²⁺ on the viability of HMC3. The neurotoxicity of Cd²⁺ and the effect of celastrol on the corresponding neurotoxicity induced by Cd²⁺ were analyzed by nitric oxide (NO) test, lipid peroxidation (MDA) test, and Western blotting. When the concentration of Cd²⁺ reached 40 μmol/L, the inhibition rate of HMC3 cell proliferation was (57.17±8.23)% (P < 0.01, n=5), compared with the control group. The cell activity continued to reduce when the Cd²⁺ concentration further increased. When the concentration of Cd²⁺ was higher than 40 μmol/L, the cell membrane of HMC3 was significantly damaged, and the damage was dose-dependent. Upon increasing the Cd²⁺ concentration, the cell morphology began to change and the adhesion also became worse. Cd²⁺ significantly increased the amount of NO released by HMC3 cells, while celastrol effectively inhibited the NO release of HMC3 cells induced by Cd²⁺. Cd²⁺ greatly increased the release of MDA in HMC3 cells, and the level of MDA decreased rapidly upon the addition of 10^-7 mol/L celastrol. Cd²⁺ increased the expression of p-PI3K protein, and the levels of p-PI3K protein and p-AKT protein were inhibited by the addition of celastrol (10^‒7 mol/L, 10^‒6 mol/L), thus preventing cell apoptosis. In conclusion, celastrol inhibits Cd²⁺ induced microglial cytotoxicity and plays a neuroprotective role.
Anti-Inflammatory Agents/pharmacology* ; Apoptosis ; Cadmium/toxicity* ; Nitric Oxide/pharmacology* ; Pentacyclic Triterpenes ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt/metabolism* ; Triterpenes/pharmacology*

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*

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

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

Tumor is one of the major diseases threatening human health in the 21st century. Surgical resection, radiotherapy, chemotherapy and targeted therapy are the main clinical treatments for solid tumors. However, these methods are unable to eradicate tumor cells completely, and easily lead to the recurrence and progression of tumor. Tumor immunotherapy is a novel treatment that uses human immune system to control and kill tumor by enhancing or restoring anti-tumor immunity. Tumor immunotherapy has shown to produce long-lasting responses in large numbers of patients, and thereby adoptive immunotherapy and immune checkpoint inhibitors could induce remarkable antigen-specific immune responses. Tumor infiltrating lymphocytes (TILs) are highly heterogeneous lymphocytes existing in tumor tissues and play a crucial role in host antigen-specific tumor immune response. Recent studies show that TILs are closely related to the prognosis of patients during the processes of tumorigenesis and treatment. Adoptive immunotherapy mediated by TILs has displayed favorable curative effect in many solid tumors. This paper reviews the recent progress of TILs in solid tumors.
Humans ; Immunotherapy ; Lymphocytes ; Lymphocytes, Tumor-Infiltrating ; Neoplasms ; Prognosis

Objective To evaluate the accuracy of different methods in detecting free amino acids in plasma.Method 40 blood samples from healthy volunteers were analyzed by an automatic amino acid analyzer ( Li+system) and the results compared with previous reports using other analyzers.Results The results ob-tained by this analyzer for major amino acids [asparagine (Asn), glutamic acid (Glu), glutamine (Gln), valine (Val), tyrosine (Tyr), phenylalanine (Phe), ornithine (Orn), arginine (Arg)] were similar with those previously reported using other amino acid analyzers ( all P>0.05 ) and liquid chromatography tandem-mass spectrometry (LC-MS/MS) (all P>0.05).Except for Glu and Tyr, the results for major amino acids showed large deviation compared to the results from high performance liquid chromatography ( HPLC) ( all P<0.05).Conclusion The amino acid analyzer (Li+) and LC-MS/MS (iTRAQ kit) could accurately detect free amino acids in plasma.