In previous studies,low expression of human epidermal growth factor receptor 2(HER2) was considered ineffective against HER2-targeted therapy.After the announcement of the efficacy of new antibody conjugated drug,Detrastuzumab in the treatment of breast cancer with low expression of HER2,the diagnosis and treatment options of breast cancer patients with low expression of HER2 have become the focus of breast cancer experts.In order to standardize the clinical rational diagnosis and treatment of breast cancer with low expression of HER2,the Breast Oncology Group of Heilongjiang Medical Association,referring to the latest clinical research at home and abroad and the consensus of experts at home and abroad,formed the consensus of breast cancer with low expression of HER2 clinicopathological diagnosis experts after the discussion by the expert group in Heilongjiang province,to guide clinicians to make diagnosis and treatment decisions for breast cancer patients with low expression of HER2,so as to improve the survival and prognosis of patients.The consensus mainly includes the definition and interpretation of breast cancer with low expression of HER2,factors influencing the results of HER2 low expression,new detection methods,clinicopathological and molecular biological characteristics,and clinical diagnosis and treatment guidance for breast cancer patients with low expression of HER2,which systematically and comprehensively demonstrates the consensus of clinicopathological diagnosis and treatment for breast cancer with low expression of HER2.

Objective The critical genes associated with exhausted CD8⁺T cells were screened and validated by mapping the single-cell transcriptome profile of high-grade serous ovarian cancer(HGSOC). Methods The specific subtypes of T cells in the tumor microenvironment were analyzed using the single-cell sequencing data from the early stage of laboratory(SRA database:PRJNA756768)and integrating 5 HGSOC sequencing from the database,and the differentiation trajectory of T cell subsets was explored through pseudotime analysis.Differential gene enrichment was used to determine immunosuppressed CD8⁺IL-2^Low and CD8⁺IFN-γ^LowT cell subsets and differential genes,and candidate molecules closely related to exhausted CD8⁺T cells were screened based on patient prognosis.Flow cytometry was used to analyze the expression of PHLDA1 on CD8⁺T cells,CD4⁺T cells and Treg cells during the activation to exhaustion process of T cells in human PBMCs.ELISA was used to detect the levels of IFN-γ and IL-2 secreted by CD8⁺T cells in PHLDA1^High and PHLDA1^Low.Finally,flow cytometry was used to analyze the association between PHLDA1 and exhausted markers PD-1 and TIM-3. Results The results showed that T cells were grouped in three ways:(1)IL-2^High and IL-2^Low;(2)IFN-γ^High and IFN-γ^Low;and(3)exhausted and cytotoxic CD8⁺T cells.Subsequently,the intersection of its differentially expressed genes was taken,and the key gene PHLDA1 was ultimately screened.Flow cytometry analysis suggested that during the process of T cell activation to exhaustion,the expression of PHLDA1 continued to increase on CD8⁺T cells,CD4⁺T cells and Treg cells;The ELISA results showed that the levels of IFN-γ and IL-2 secreted by CD8⁺PHLDA1^HighT cells were significantly lower than those of CD8⁺ PHLDA1^LowT cells.Meanwhile,the CD8⁺PHLDA1^HighT cell subset could simultaneously cover the exhausted T cell types of CD8⁺TIM-3⁺ and CD8⁺PD-1⁺. Conclusion Based on single-cell sequencing data,this study identified PHLDA1 as a key molecule responsible for CD8⁺T cell exhaustion in OC,providing new insights for immunotherapy of OC.

Objective The Objective of this study was to explore the key genes regulating the metastasis of breast cancer,determine the effects of DLX2 on proliferation,migration,invasion,and apoptosis of breast cancer cells,and explore the role and mechanism of DLX2 in regulating the characteristics of breast cancer stem cells. Methods A DLX2 gene knockdown breast cancer MCF7 cell line was constructed.The cell viability was detected in breast cancer cells by CCK-8 assay,apoptosis was detected in breast cancer cells by flow cytometry,cell migration and invasive abilities were detected by Transwell assay,the expression of SOX4 protein was detected by immunofluorescence(IF)in breast cancer cells and xenografts,the expression of CD44 and ALDH1 protein was detected in breast cancer cells and xenografts by Western blot,apoptosis was detected in xenografts by TUNEL assay,and the malignancy degree of tumor tissues was assessed by HE staining. Results After knocking down DLX2,the cell viability decreased(P＜0.001),apoptosis increased(P＜0.001),and cell migration and invasion abilities decreased in breast cancer cells(P＜0.05).The results of IF showed that the expression of SOX4 was inhibited.The results of Western blot showed a decrease in the expression of CD44 and ALDH1 proteins in breast cancer cells,which are cellular stemness markers(P＜0.05).In the Balb/c nude mouse breast cancer transplantation tumor model,the volume of xenografts in the sh-DLX2 group was significantly smaller than that in the model group(P＜0.001),the xenografts grew slowly,and the volume and weight of xenografts were also lower than those of the model group(P＜0.05).Apoptosis in the sh-DLX2 group was higher than that in the model group,and the expression of SOX4,CD44 and ALDH1 was consistent with the cellular level,all of which were inhibited(P＜0.05). Conclusion DLX2 inhibits proliferation,migration and invasion of breast cancer cells,promotes apoptosis of breast cancer cells,and regulates the characteristics of breast cancer stem cells through SOX4.

Objective This Objective of this study was to investigate the effects of long chain non-coding RNA GAS5(lncRNA GAS5)on the proliferation,invasion ability and PTEN/Akt/mTOR signaling pathway of cervical cancer cells,and to elucidate the possible mechanism of lncRNA GAS5 in cervical cancer. Methods Real-time quantitative reverse transcription polymerase chain reaction(qRT-PCR)was used to detect the levels of lncRNA GAS5 in human cervical cancer HeLa cells,C33A cells,Caski cells,Siha cells and normal cervical epithelial End1/E6E7 cells.HeLa cells were divided into the blank control group(BC group),negative control group(NC group)and overexpressing lncRNA GAS5 group(GAS5 group);Siha cells were divided into the blank control group(BC group),negative control siRNA group(si-NC group)and siRNA-lncRNA GAS5 group(si-GAS5).The CCK8 assay was used to measure proliferation of cervical cancer cells.The Transwell was used to measure the invasion and migration capabilities of cervical cancer cells.Western blot was used to determine the expression of proliferating cell nuclear antigen(PCNA),matrix metalloproteinase(MMP)-2,MMP-9,PTEN,Akt,phosphorylated Akt(p-Akt),mTOR and p-mTOR proteins in cervical cancer cells. Results The results showed that the levels of lncRNA GAS5 in HeLa cells,C33A cells,Caski cells and Siha cells were lower than that in End1/E6E7 cells(P＜0.001).Compared with the NC group,overexpression of lncRNA GAS5 in HeLa cells resulted in a decrease in the cell proliferation,invasion,and migration abilities,as well as a decrease in the levels of PCNA,MMP-2,MMP-9,p-Akt,and p-mTOR proteins(P＜0.001),while an increase in the level of PTEN protein(P＜0.001).Compared with the si-NC group,inhibition of lncRNA GAS5 expression in Siha cells resulted in increased the cell proliferation,invasion,and migration abilities,as well as increased the levels of PCNA,MMP-2,MMP-9,p-Akt,and p-mTOR proteins(P＜0.001),while decreased the level of PTEN protein(P＜0.001). Conclusion The level of lncRNA GAS5 in cervical cancer cells is reduced,and lncRNA GAS5 can inhibit the proliferation,invasion and migration abilities of cervical cancer cells,as well as activate the PTEN/Akt/mTOR signaling pathway.

Objective The Objective of this study was to investigate the effects of propofol on glycolysis of lung cancer,and to further explore its potential mechanism of inhibiting glycolysis in lung cancer through glucose transporter 4(GLUT4). Methods Human lung cancer A549 cells and mouse lung cancer LLC cells were cultured,and the experimental groups were set as the blank control group(Control group)and propofol(10 μmol/L)group(Propofol group).The CCK-8 assay was used to detect cell viability;Immunofluorescence(IF)was used to detect the expression of Ki-67 in lung cancer cells and A549 cell xenografts.Extracellular acidification rate(ECAR)and mitochondrial oxygen consumption(OCR)assays were used to detect the cellular metabolic levels;ELISA was used to detect the cell lactate and pyruvate content;Molecular docking experiments were used to detect the binding ability of GLUT4 with propofol using CB-Dock online tool;The glucose uptake kit was used to detect glucose uptake;Western blot was used to detect the expression of GLUT4,HK2,and PFK1 proteins in lung cancer cells. Results The cell viability of A549 cells(0.661±0.052)and LLC cells(0.632±0.033)in the propofol group was significantly inhibited by 10 μmol/L of propofol in lung cancer cells(P＜0.001).Compared with the control group,the average fluorescence intensity of Ki-67 in A549 and LLC positive cells(0.663±0.064 and 0.540±0.070)was significantly suppressed(P＜0.001).The ELISA results showed that compared with the control group,the levels of lactate and pyruvate in the propofol group decreased(P＜0.001),and under the action of propofol,the glucose uptake ability of cells decreased(P＜0.001).Molecular docking experiments using the CB-Dock online tool showed that GLUT4 had the strongest binding force with propofol.The results of Western blot showed a decrease in the expression of GLUT4 and its downstream HK2 and PFK1 proteins.After transient transfection and knockdown of GLUT4,cellular lactate(P＜0.001)and pyruvate content(P＜0.01)decreased,glucose uptake capacity reduced,and the inhibitory effect of propofol on glycolysis disappeared.In A549 cell xenografts,the weight of xenografts in the propofol group was significantly smaller than that of the model group(P＜0.001).Compared with the model group,the lactate content and pyruvate content decreased in the propofol group(P＜0.001). Conclusion Propofol can inhibit the proliferation of lung cancer cells and the progression of A549 cell xenografts in bearing mice by inhibiting the glycolysis of lung cancer cells,and its mechanism may be related to the targeted effect of GLUT4 on the glycolysis of lung cancer cells.

Objective The aim of this study was to compare the clinical efficacy of hepatic artery chemoembolization combined with two-stage surgical resection and simple hepatic arterial chemoembolization in the treatment of unresectable advanced liver cancer in the Chinese population. Methods A clinical controlled study literature was collected in China through computer and manual retrieval on the combination of hepatic arterial chemoembolization with two-stage surgery and hepatic arterial chemoembolization alone for the treatment of unresectable liver cancer.A Meta-analysis was conducted on 17 experiments that met the inclusion criteria using Revman 5.2 software and applying heterogeneity test analysis. Results Compared with the combination of hepatic artery chemoembolization and phase II surgery,simple hepatic arterial chemoembolization had higher postoperative 1-year,2-year and 3-year risk of death (OR=2.82,2.22 and 3.40,P＜0.05).In addition,under the same conditions of chemoembolization drugs,compared with the combination of hepatic arterial chemoembolization and phase II s,simple hepatic arterial chemoembolization had higher postoperative 1-year and 3-year risk of death (OR=6.74,4.64,P＜0.05).Compared with simple hepatic arterial chemoembolization,thehe combination of hepatic arterial chemoembolization and phase II surgery had a lower 1-year disease progression risk (OR=0.46),but there was no significant difference(P＞0.05).The disease progression risk continued to decrease 2 years after surgery (OR=0.29,P＜0.05). Conclusion The long-term efficacy of hepatic arterial chemoembolization combined with two-stage surgery in the treatment for unresectable liver cancer is better than that of hepatic arterial chemoembolization alone,whic can effectively improve patients survival and reduce disease progression rate.

Objective The aim of this study was to analyze the predictive value of an immune scoring model based on immune cell infiltration for the efficacy and prognosis of immunotherapy in early gastric cancer. Methods The gene expression data and related clinical parameters of 167 early gastric cancer patients were downloaded from the Cancer Genome Atlas(TCGA)as the training set.The clinical information of 92 early gastric cancer patients who first visited our hospital from January 2017 to January 2020 was collected as a validation set.The infiltration of 22 immune cells in tumor tissues was calculated by the Cibersort software.The key predictive factors for early gastric cancer patients were further screened and determined by lasso analysis and multivariate Cox regression analysis.The eligible immune cells were used to construct the prognostic risk scoring model and verify it.Based on the risk model,a nomograph model was established to predict the probability of death and treatment failure in early gastric cancer patients,and evaluate the differentiation,accuracy,and reliability of the model. Results There was no statistically significant difference in the general information of patients between the training set and the validation set(P＞0.05).Compared with normal tissues,the content of CD8⁺T cells,activated memory CD4⁺T cells,M0 macrophages,M1 macrophages,resting dendritic cells,and activated dendritic cells in early gastric cancer tumor tissues decreased.The contents of regulatory T cells(Treg cells)and eosinophils increased,and the difference was statistically significant(P＜0.05).The LASSO analysis further screened five types of infiltrating immune cells,including activated memory CD4⁺T cells,M1 macrophages,Treg cells,activated dendritic cells and eosinophils.The survival curve results showed that the immune scoring model could effectively distinguish the survival time of patients.The total score of the prognostic nomogram model was 274,corresponding to risk of death of 72%.The total score of the treatment effect nomograph model was 307,corresponding to a 75% risk of ineffective treatment.The model validation results showed that the nomograph model has high discrimination,accuracy and reliability. Conclusion The immune scoring model based on immune cell infiltration has a certain predictive value for the efficacy and prognosis of immunotherapy in patients with early gastric cancer.

Tumor has become a major social problem threatening human life and health,and the multimodal integrated treatment method has greatly improved the prognosis and life quality of cancer patients. Studies have shown that cancer patients are prone to emotional disorders such as depression and anxiety,and tumor-related depression has directly affected the efficacy and prognosis of patients.This article focuses on the epidemiology,mechanism,and clinical diagnosis and treatment characteristics of tumor related depression,and reviews domestic and foreign research in order to provide references for the diagnosis and treatment of tumor related depression and improve the treatment effect of tumor patients.

Hirsutine,an indole alkaloid extracted from the traditional Chinese herb Uncaria,has exhibits diverse pharmacological activities,including antihypotensive,antiinfective,and cardioprotection.In cervical cancer,breast cancer,colon cancer,and other malignant tumors,hirsutine has effects on anti-tumor by regulating cell apoptosis,immune regulation and other pathways,laying the foundation for the application of hirsutine in the field of cancer therapy.This article reviews relevant literature both domestically and internationally to elucidate the research progress of hirsutine in anti-tumor therapy,providing new ideas and strategies for cancer treatment.