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*

Objective To investigate the effect of resveratrol (RSV) on epithelial-mesenchymal transition of MDA-MB-231 cells by down-regulating POLD1 expression. Methods CCK-8 was used to detect the effect of RSV on the activity of MDA-MB-231 cells. POLD1-OE and POLD1-NC cell lines were constructed by transfecting MDA-MB-231 cells with recombinant lentivirus. Western blot was used to detect the expression of POLD1, E-cadherin, N-cadherin and Vimentin after RSV treatment. Transwell invasion experiment and the scratch test were used to detect the cells invasion and migration abilities of each experimental group. Results RSV could significantly inhibit the survival of MDA-MB-231 cells, reduce the expression of POLD1, N-cadherin and Vimentin, increase the expression of E-cadherin, and inhibit the abilities of cell invasion and migration. Increasing the POLD1 expression could reduce the above-mentioned biological effects of RSV on MDA-MB-231 cells. Conclusion RSV could significantly inhibit the viability and EMT of MDA-MB-231 cells by down-regulating the expression of POLD1.

Objective:To analyze the pathologic features of responses to neoadjuvant immunotherapy of squamous cell carcinoma (SCC) of the lung.Methods:The study included 31 patients with resected lung SCC post neoadjuvant immunotherapy. All patients were recruited from the neoadjuvant anti-PD-1 (Sintilimab) phase Ⅰb clinical trial (ChiCTR-OIC-17013726). The histopathological morphology and different degrees of pathologic response to immunotherapy were evaluated basing on irPRC standard.Results:According to the percentage of residual viable tumor (% RVT), pathologic responses of complete pathologic response (cPR), major pathologic response (MPR) and non-MPR were noted in 19% ( n=6), 29% ( n=9), and 52% ( n=16) of patients respectively. In addition, extensive immune activation phenomena (immune cell infiltration, including infiltration of lymphocytes, plasma cells, foamy macrophages, lymphocyte aggregation and tertiary lymphoid structures formation) and tissue repair features (giant cells, granuloma formation, proliferative fibrosis and neovascularization) were observed in tumor regression bed. Conclusions:Neoadjuvant immunotherapy has favorable effect on lung SCC. Pathologic assessment of resected lung cancer specimens after neoadjuvant immunotherapy shows unique histopathological features consistent with its mechanism.

Objective:To investigate the effect of esculin on the proliferation of triple negative breast cancer cells and its molecular mechanism.Methods:MDA-MB-231 cells were treated with 28, 56, 112, 225, 450 and 900 μmol/L of esculin for 24, 48 and 72 h, respectively, and the cell viability was detected by cell counting kit 8 (CCK-8) assay. In addition, MDA-MB-231 cells were treated with 0, 225, 450 and 900 μmol/L of esculin for 48 h. And then the changes in cell morphology were observed by inverted microscope. The clone-forming ability was detected by colony formation assay. The mRNA expression levels of FBI-1, p53 and p21 were detected using real-time fluorescence quantitative polymerase chain reaction. The protein expression levels of FBI-1, p53, p21 and Ki67 were detected by western blot.Results:Compared with the blank control group, the cell viability of MDA-MB-231 cells that treated with esculin significantly decreased in a dose-dependent and time-dependent manners. After treatment with esculin, MDA-MB-231 cells shrunk, flattened, adhered poorly to the culture dish and the cell spacing became larger. Meanwhile, shedding and incomplete cells appeared, of which 900 μmol/L of esculin treatment group showed the most dramatic changes. In addition, the colony formation ratios were decreased to (77.18±5.13)%, (65.94±4.98)% and (45.92±3.70)% in the 225, 450 and 900 μmol/L of esculin treatment groups compared with blank control, respectively ( P<0.01). Furthermore, the mRNA and protein expressions of FBI-1 increased, while the levels of p53 and p21 mRNA and protein, as well as the protein expression of Ki67 decreased in a concentration-dependent manner ( P<0.01). Conclusion:Esculin may regulate cell cycle-related p53-p21 pathway via FBI-1 mediated DNA replication, thus inhibit the proliferation of triple negative breast cancer cells.

Objective:To investigate the effect of esculin on the proliferation of triple negative breast cancer cells and its molecular mechanism.Methods:MDA-MB-231 cells were treated with 28, 56, 112, 225, 450 and 900 μmol/L of esculin for 24, 48 and 72 h, respectively, and the cell viability was detected by cell counting kit 8 (CCK-8) assay. In addition, MDA-MB-231 cells were treated with 0, 225, 450 and 900 μmol/L of esculin for 48 h. And then the changes in cell morphology were observed by inverted microscope. The clone-forming ability was detected by colony formation assay. The mRNA expression levels of FBI-1, p53 and p21 were detected using real-time fluorescence quantitative polymerase chain reaction. The protein expression levels of FBI-1, p53, p21 and Ki67 were detected by western blot.Results:Compared with the blank control group, the cell viability of MDA-MB-231 cells that treated with esculin significantly decreased in a dose-dependent and time-dependent manners. After treatment with esculin, MDA-MB-231 cells shrunk, flattened, adhered poorly to the culture dish and the cell spacing became larger. Meanwhile, shedding and incomplete cells appeared, of which 900 μmol/L of esculin treatment group showed the most dramatic changes. In addition, the colony formation ratios were decreased to (77.18±5.13)%, (65.94±4.98)% and (45.92±3.70)% in the 225, 450 and 900 μmol/L of esculin treatment groups compared with blank control, respectively ( P<0.01). Furthermore, the mRNA and protein expressions of FBI-1 increased, while the levels of p53 and p21 mRNA and protein, as well as the protein expression of Ki67 decreased in a concentration-dependent manner ( P<0.01). Conclusion:Esculin may regulate cell cycle-related p53-p21 pathway via FBI-1 mediated DNA replication, thus inhibit the proliferation of triple negative breast cancer cells.

Objective: To explore the feasibility of 7, 12-dimethylbenz[a] anthracene (DMBA) induced tree shrew breast cancer model, and compare the effects of two administration modes by gavage and mammary gland injection. Methods: A total of 40 tree shrews were randomly divided into two groups (20 animals per group): DMBA gavage group and mammary gland injection group. DMBA was dissolved in edible vegetable oil. For gavage group, tree shrews were administered with DMBA solutions (15 mg/kg) by gavage once a day. For mammary gland injection group, DMBA solution (10 mg/kg) was injected into the mammary fat pad of tree shrews, and the injection was performed for a total of 3 times. From the first administration of DMBA, medroxyprogesterone acetate (MPA, 100 mg/kg) was intramuscularly injected into the muscles of the lateral thighs of tree shrews at the same time, for a total of 5 times. The tumorigenesis and survival of tree shrews were monitored. The tumor histological morphology was observed by HE staining. The expression of estrogen receptor (ER), progesterone receptor (PR), cytokeratin5/6 (CK5/6) and human epidermal factor receptor-2 (HER-2) was detected by immunohistochemical staining. Results: In the gavage group, there were 10 deaths, and 4 tree shrews developed mammary tumors with 20.0% (4/20) tumor formation rate. The success rate of mammary cancer modeling was 10.0% (2/20), and the tumor formation time was 197.3±15.1 days. In the mammary gland injection group, there were 8 tree shrews died, and 9 tree shrews formed tumors with 45.0% (9/20) tumor formation rate. The success rate of mammary cancer modeling was 40.0% (8/20), and the tumor formation time was 71.8±19.0 days. There was no significant difference in mortality and tumor formation rate (P>0.05) between the two groups (all P>0.05). However, in the mammary gland injection group, the success rate of mammary cancer modeling was significantly higher than that in the gavage group (P<0.05), whereas the tumor formation time was markedly shorter than that in the gavage group (P<0.01). The pathological types in the gavage group included ductal hyperplasia, intraductal papilloma and ductal carcinoma in situ, while those in the breast injection group included intraductal papilloma and ductal carcinoma in situ. In both groups, immunohistochemical staining showed the negative expression of HER-2 but positive expression of ER, PR and CK5/6 with varying degrees. Conclusion Both the DMBA gavage and mammary gland injection can successfully establish the tree shrew breast cancer model, and the modeling effect of mammary gland injection is better than gavage.

Objective To explore the feasibility of 7,12?dimethylbenz[ a] anthracene ( DMBA) induced tree shrew breast cancer model, and compare the effects of two administration modes by gavage and mammary gland injection. Methods A total of 40 tree shrews were randomly divided into two groups (20 animals per group): DMBA gavage group and mammary gland injection group. DMBA was dissolved in edible vegetable oil. For gavage group, tree shrews were administered with DMBA solutions (15 mg／kg) by gavage once a day. For mammary gland injection group, DMBA solution (10 mg／kg) was injected into the mammary fat pad of tree shrews, and the injection was performed for a total of 3 times. From the first administration of DMBA, medroxyprogesterone acetate (MPA, 100 mg／kg) was intramuscularly injected into the muscles of the lateral thighs of tree shrews at the same time, for a total of 5 times. The tumorigenesis and survival of tree shrews were monitored. The tumor histological morphology was observed by HE staining. The expression of estrogen receptor (ER), progesterone receptor ( PR), cytokeratin5／6 ( CK5／6) and human epidermal factor receptor?2 (HER?2) was detected by immunohistochemical staining.Results In the gavage group, there were 10 deaths, and 4 tree shrews developed mammary tumors with 20.0%( 4／20) tumor formation rate. The success rate of mammary cancer modeling was 10.0%(2／20), and the tumor formation time was 197.3±15.1 days. In the mammary gland injection group, there were 8 tree shrews died, and 9 tree shrews formed tumors with 45.0%( 9／20) tumor formation rate. The success rate of mammary cancer modeling was 40.0%(8／20), and the tumor formation time was 71.8±19.0 days. There was no significant difference in mortality and tumor formation rate (P＞0.05) between the two groups (all P＞0.05). However, in the mammary gland injection group, the success rate of mammary cancer modeling was significantly higher than that in the gavage group (P＜0.05), whereas the tumor formation time was markedly shorter than that in the gavage group ( P＜0.01). The pathological types in the gavage group included ductal hyperplasia, intraductal papilloma and ductal carcinoma in situ, while those in the breast injection group included intraductal papilloma and ductal carcinoma in situ. In both groups, immunohistochemical staining showed the negative expression of HER?2 but positive expression of ER, PR and CK5／6 with varying degrees. Conclusion Both the DMBA gavage and mammary gland injection can successfully establish the tree shrew breast cancer model, and the modeling effect of mammary gland injection is better than gavage.

Objective To explore the feasibility of 7,12?dimethylbenz[ a] anthracene ( DMBA) induced tree shrew breast cancer model, and compare the effects of two administration modes by gavage and mammary gland injection. Methods A total of 40 tree shrews were randomly divided into two groups (20 animals per group): DMBA gavage group and mammary gland injection group. DMBA was dissolved in edible vegetable oil. For gavage group, tree shrews were administered with DMBA solutions (15 mg／kg) by gavage once a day. For mammary gland injection group, DMBA solution (10 mg／kg) was injected into the mammary fat pad of tree shrews, and the injection was performed for a total of 3 times. From the first administration of DMBA, medroxyprogesterone acetate (MPA, 100 mg／kg) was intramuscularly injected into the muscles of the lateral thighs of tree shrews at the same time, for a total of 5 times. The tumorigenesis and survival of tree shrews were monitored. The tumor histological morphology was observed by HE staining. The expression of estrogen receptor (ER), progesterone receptor ( PR), cytokeratin5／6 ( CK5／6) and human epidermal factor receptor?2 (HER?2) was detected by immunohistochemical staining.Results In the gavage group, there were 10 deaths, and 4 tree shrews developed mammary tumors with 20.0%( 4／20) tumor formation rate. The success rate of mammary cancer modeling was 10.0%(2／20), and the tumor formation time was 197.3±15.1 days. In the mammary gland injection group, there were 8 tree shrews died, and 9 tree shrews formed tumors with 45.0%( 9／20) tumor formation rate. The success rate of mammary cancer modeling was 40.0%(8／20), and the tumor formation time was 71.8±19.0 days. There was no significant difference in mortality and tumor formation rate (P＞0.05) between the two groups (all P＞0.05). However, in the mammary gland injection group, the success rate of mammary cancer modeling was significantly higher than that in the gavage group (P＜0.05), whereas the tumor formation time was markedly shorter than that in the gavage group ( P＜0.01). The pathological types in the gavage group included ductal hyperplasia, intraductal papilloma and ductal carcinoma in situ, while those in the breast injection group included intraductal papilloma and ductal carcinoma in situ. In both groups, immunohistochemical staining showed the negative expression of HER?2 but positive expression of ER, PR and CK5／6 with varying degrees. Conclusion Both the DMBA gavage and mammary gland injection can successfully establish the tree shrew breast cancer model, and the modeling effect of mammary gland injection is better than gavage.

Objective To investigate the epidemiological characteristics of emergency critical illness and disease spectrum in emergency department of a hospital in Beijing. Methods A retrospective study was conducted. The data of 3 176 critically ill patients aged ≥ 14 years old admitted to the emergency room of Xuanwu Hospital Capital Medical University from January 1st to December 31st in 2017 were analyzed, including gender, age, clinical time, discharge diagnosis, outcomes, etc. To analyze the epidemiological characteristics and disease spectrum distribution of emergency critically ill patients, annual and daily 24-hour emergency visits in 2017 were analyzed. Results Among the 3 176 cases of acute critical illness, there were more males than females (1 824 vs. 1 352, 1.35 : 1); the age ranged from 14 to 100 years old, with an average of (66.52±17.18) years old; the highest incidence age was 75-89 years old (35.2%, 516 males and 603 females), followed by 60-70 years old (30.0%, 572 males and 381 females). The top four prevalence diseases in the emergency critical disease spectrum were cardiovascular diseases [41.8%, 716 males and 610 females, age (70.25±15.08) years old], nervous system diseases [26.7%, 502 males and 346 females, age (60.28±17.57) years old], respiratory disease [12.3%, 226 males and 166 females, age (72.96±16.23) years old] and digestive system diseases [5.6%, 119 males and 60 females, age (65.40±17.96) years old], accounting for 86.4% of the total. There were more males than females (all P < 0.05), and the age difference was statistically significant (F = 84.094, P < 0.001). Arrhythmia was the most common cardiovascular disease (16.7%), followed by acute coronary syndrome (12.0%) and heart failure (9.1%); the main nervous system diseases were stroke (20.9%); respiratory diseases mainly included severe pneumonia (8.3%); digestive system diseases were mainly with digestive tract bleeding (4.4%). The high incidence of acute critical illness in the emergency department occurred in winter (287 cases in December and 277 cases in January) and the early stage of spring (282 cases in March). The daily peak period was midday and at night, especially from 18:00 to 23:00 (163 cases at 18:00, 173 cases at 19:00, 172 cases at 20:00, 186 cases at 21:00, 167 cases at 22:00, 169 cases at 23:00). The average treatment time of critically ill patients in emergency room was 1.5 days (the longest was 23.0 days, the shortest was 6 minutes), among them, 85.6% of the patients could be discharged from the emergency within 3 days, and 1.9% of the patients stayed in the emergency for more than 7 days. There were 305 deaths (9.6%), mainly among the elderly, with an average age of (71.10±16.08) years old. Conclusions Cardiovascular and cerebrovascular diseases, respiratory and digestive diseases are the main causes of acute critical diseases in department of emergency of Xuanwu Hospital Capital Medical University in 2017. Male and elderly patients are more common; different types of acute and severe patients tend to attack at different ages.

Background and purpose: Factor that binds to the inducer of short transcripts of human immuno-deficiency virus-1 (FBI-1) in a variety of malignant tumors showed high expression levels, which may be closely related to tumor proliferation and differentiation, angiogenesis, metastasis, but its relationship with breast cancer has not been fully elucidated. The purpose of this study was to investigate the expression of FBI-1 in breast cancer cells, and to study the effect of FBI-1 gene expression on the proliferation of breast cancer cells and its possible mechanism. Methods:Real-time fluorescent quantitative polymerase chain reaction (RTFQ-PCR) and Western blot analysis were applied to detect FBI-1 expression in normal human mammary epithelial cell line MCF-10A and breast cancer cell MCF-7. RNA interference method was used to down-regulate FBI-1 expression in MCF-7 cells. The cell proliferation was measured by CCK-8 kit and colony formation assay. RTFQ-PCR and Western blot were used to detect the expression of FBI-1 and NF-κBp65 in MCF-7 cells before and after the interference of FBI-1 expression. Results: The expression of FBI-1 was higher in breast cancer cells than that in normal human mammary epithelial cells (P<0.05). The effects of FBI-1 down-regulation inhibited proliferation in MCF-7 cells (P<0.05). At the same time, after inhibition of FBI-1, the NF-κBp65 mRNA and protein expression levels were significantly decreased (P<0.05). Conclusion: FBI-1 is highly expressed in breast cancer cells. Down-regulated FBI-1 expression can inhibit the proliferation of breast cancer cells,and its mechanism may be related to the inhibition of NF-κB signaling pathway.