Purpose This study aimed to evaluate the consistency of human epidermal growth factor receptor 2(HER2)status between primary breast cancer lesions and lung metastatic lesions and to establish a prognostic model for predicting the survival rate of HER2 low expression(HER2-low)breast cancer patients with lung metastasis.Methods Clinicopathological data from a cohort of 252 patients with breast cancer and lung metastasis were retrospec-tively analyzed.Results 50.00％of the patients had HER2-low expression in metastatic lesions,and HER2-low ex-pression was the most prevalent subgroup in both primary and metastatic lesions.A discordance in HER2 status be-tween primary and metastatic sites was observed in 28.07％of cases.The most frequent shift was from HER2-zero in the primary tumor to HER2-low expression in the metastasis(12.28％of all cases).Estrogen receptor(ER)status,menopausal status,and histological type were identified as independent prognostic factors for overall survival(OS)by univariate and multivariate Cox regression analyses.A prognostic model incorporating these factors was constructed to predict 3-year and 5-year survival.The model demonstrated area under the curve(AUC)values of 0.765 and 0.780 for 3-year and 5-year OS in the training cohort,and 0.667 and 0.706 in the validation cohort,respectively.Conclu-sion HER2-low expression is the most common subtype among breast cancer patients with lung metastasis.The ob-served shift from HER2-zero in primary lesions to HER2-low in metastases underscores the clinical necessity of re-biop-sy at metastatic sites.The developed prognostic model effectively predicts OS in this patient population.

Neutrophils are important effector cells of innate immunity and play a key role in immune defense.When pathogens invade, neutrophils can kill microorganisms by phagocytosis and degradation through synthesis of reactive oxygen species, degranulation or release of antimicrobial peptides.In recent years, studies have discovered a new neutrophil defense mechanism that captures microorganisms by forming neutrophil extracellular traps (NETs). NETs are DNA networks that are released outside the cell after depolymerization and diffusion of chromatin in the nucleus of neutrophils.Different stimuli can activate different patterns of NETs formation, the essence of which is whether the release of neutrophil contents affects its own phagocytic function.NETs were initially thought to be a kind of mediator with bactericidal effect, which can wrap and remove bacteria and fungi in keratitis, preventing bacteria from ascending into the brain, but it will lead to irreversible damage to the cornea.At the same time, studies have found that NETs also have pro-inflammatory effects and play a role in the development of a variety of inflammatory eye diseases, including dry eye, diabetic retinopathy, glaucoma, and age-related macular degeneration, etc.Currently, more and more studies are focusing on the role of NETs in autoimmune eye diseases, that is, NETs can generate new antigens that are beneficial to autoimmune eye diseases, but also increase tissue damage.This review summarizes the related studies on NETs, focuses on describing the formation and role of NETs in ocular diseases, and provides new ideas for targeted treatment of ocular diseases.

Neutrophils are important effector cells of innate immunity and play a key role in immune defense.When pathogens invade, neutrophils can kill microorganisms by phagocytosis and degradation through synthesis of reactive oxygen species, degranulation or release of antimicrobial peptides.In recent years, studies have discovered a new neutrophil defense mechanism that captures microorganisms by forming neutrophil extracellular traps (NETs). NETs are DNA networks that are released outside the cell after depolymerization and diffusion of chromatin in the nucleus of neutrophils.Different stimuli can activate different patterns of NETs formation, the essence of which is whether the release of neutrophil contents affects its own phagocytic function.NETs were initially thought to be a kind of mediator with bactericidal effect, which can wrap and remove bacteria and fungi in keratitis, preventing bacteria from ascending into the brain, but it will lead to irreversible damage to the cornea.At the same time, studies have found that NETs also have pro-inflammatory effects and play a role in the development of a variety of inflammatory eye diseases, including dry eye, diabetic retinopathy, glaucoma, and age-related macular degeneration, etc.Currently, more and more studies are focusing on the role of NETs in autoimmune eye diseases, that is, NETs can generate new antigens that are beneficial to autoimmune eye diseases, but also increase tissue damage.This review summarizes the related studies on NETs, focuses on describing the formation and role of NETs in ocular diseases, and provides new ideas for targeted treatment of ocular diseases.

Objective:To investigate the mutation spectrum of the PIK3CA gene in breast cancer, providing a new basis for the precise treatment of breast cancer with PIK3CA inhibitors.Methods:A retrospective analysis was conducted on 144 breast cancer patients who underwent biopsy before neoadjuvant therapy archived from 2015 to 2020 at the Fourth Hospital of Hebei Medical University. Next-generation sequencing (NGS) was utilized to detect the mutations of 520 genes closely related to the development of solid tumors and targeted therapies. The study compared the differences between reported mutation types and focused on analyzing the mutation status of the PIK3CA gene. The clinical and pathological characteristics, including age of onset, molecular subtypes, and Ki-67, were also analyzed. The correlation between PIK3CA mutations and clinicopathological characteristics was examined using Pearson×s chi-square test and Mann Whitney test. Logistic regression was employed to analyze factors influencing PIK3CA mutations. Kaplan-Meier survival analysis and Cox regression models were constructed using R programming.Results:Among the 144 breast cancer samples, 61 (42.3%, 61/144) exhibited PIK3CA gene mutations, of which 23 cases (53.5%, 23/43) were HER2-positive breast cancer, 28 cases (44.4%, 28/63) were luminal breast cancer, and 10 cases (27.8%, 10/36) were triple-negative breast cancer. Of the detected mutations, three hotspot mutations (H1047R, E545K, and E542K) accounted for 72.1% of the total PIK3CA mutations, with H1047R (52.4%), E545K (16.4%), and E542K (3.3%) most commonly detected. The remaining rare mutations accounted for 26.3%. Co-mutations involving PIK3CA and other genes were also observed in the cohort, occurring with TOP2A and FOXA1, while being mutually exclusive with GATA3 and BRCA2. PIK3CA mutations were significantly associated with HER2 status and were not significantly correlated with the patient′s age, menopausal status, HR status, Ki-67 index, molecular typing, TNM stage or pCR status. Likewise, no significant correlation was found between different PIK3CA mutation status and overall survival.Conclusions:This cohort study shows the overall mutation rate of PIK3CA in breast cancer and the mutation frequencies across different molecular subtypes. The findings reveal a significant correlation between PIK3CA mutations and HER2 status, which provides a new basis for the precise treatment of breast cancer with PIK3CA inhibitors.

Purpose This study aimed to evaluate the consistency of human epidermal growth factor receptor 2(HER2)status between primary breast cancer lesions and lung metastatic lesions and to establish a prognostic model for predicting the survival rate of HER2 low expression(HER2-low)breast cancer patients with lung metastasis.Methods Clinicopathological data from a cohort of 252 patients with breast cancer and lung metastasis were retrospec-tively analyzed.Results 50.00％of the patients had HER2-low expression in metastatic lesions,and HER2-low ex-pression was the most prevalent subgroup in both primary and metastatic lesions.A discordance in HER2 status be-tween primary and metastatic sites was observed in 28.07％of cases.The most frequent shift was from HER2-zero in the primary tumor to HER2-low expression in the metastasis(12.28％of all cases).Estrogen receptor(ER)status,menopausal status,and histological type were identified as independent prognostic factors for overall survival(OS)by univariate and multivariate Cox regression analyses.A prognostic model incorporating these factors was constructed to predict 3-year and 5-year survival.The model demonstrated area under the curve(AUC)values of 0.765 and 0.780 for 3-year and 5-year OS in the training cohort,and 0.667 and 0.706 in the validation cohort,respectively.Conclu-sion HER2-low expression is the most common subtype among breast cancer patients with lung metastasis.The ob-served shift from HER2-zero in primary lesions to HER2-low in metastases underscores the clinical necessity of re-biop-sy at metastatic sites.The developed prognostic model effectively predicts OS in this patient population.

Objective:To investigate the mutation spectrum of the PIK3CA gene in breast cancer, providing a new basis for the precise treatment of breast cancer with PIK3CA inhibitors.Methods:A retrospective analysis was conducted on 144 breast cancer patients who underwent biopsy before neoadjuvant therapy archived from 2015 to 2020 at the Fourth Hospital of Hebei Medical University. Next-generation sequencing (NGS) was utilized to detect the mutations of 520 genes closely related to the development of solid tumors and targeted therapies. The study compared the differences between reported mutation types and focused on analyzing the mutation status of the PIK3CA gene. The clinical and pathological characteristics, including age of onset, molecular subtypes, and Ki-67, were also analyzed. The correlation between PIK3CA mutations and clinicopathological characteristics was examined using Pearson×s chi-square test and Mann Whitney test. Logistic regression was employed to analyze factors influencing PIK3CA mutations. Kaplan-Meier survival analysis and Cox regression models were constructed using R programming.Results:Among the 144 breast cancer samples, 61 (42.3%, 61/144) exhibited PIK3CA gene mutations, of which 23 cases (53.5%, 23/43) were HER2-positive breast cancer, 28 cases (44.4%, 28/63) were luminal breast cancer, and 10 cases (27.8%, 10/36) were triple-negative breast cancer. Of the detected mutations, three hotspot mutations (H1047R, E545K, and E542K) accounted for 72.1% of the total PIK3CA mutations, with H1047R (52.4%), E545K (16.4%), and E542K (3.3%) most commonly detected. The remaining rare mutations accounted for 26.3%. Co-mutations involving PIK3CA and other genes were also observed in the cohort, occurring with TOP2A and FOXA1, while being mutually exclusive with GATA3 and BRCA2. PIK3CA mutations were significantly associated with HER2 status and were not significantly correlated with the patient′s age, menopausal status, HR status, Ki-67 index, molecular typing, TNM stage or pCR status. Likewise, no significant correlation was found between different PIK3CA mutation status and overall survival.Conclusions:This cohort study shows the overall mutation rate of PIK3CA in breast cancer and the mutation frequencies across different molecular subtypes. The findings reveal a significant correlation between PIK3CA mutations and HER2 status, which provides a new basis for the precise treatment of breast cancer with PIK3CA inhibitors.

Objective To investigate the expression of zinc finger protein 382(ZNF382)in diffuse large B-cell lymphoma(DLBCL)tissue and its relationship with clinical pathological characteristics and prognosis of DLBCL patients.Methods A total of 57 DLBCL patients admitted to the Department of Hematology,Luoyang Central Hospital from January 2014 to December 2018 were selected as the research subjects.The biopsy pathological specimens and clinical data of DLBCL patients were collected;another 20 patients of reactive proliferative lymph node tissue preserved in the Department of Pathology,Luoyang Central Hospital were taken as the control group.The expression of ZNF382 in DLBCL tissue and reactive proliferative lymph node tissue was detected by En vision two-step method.The difference of ZNF382 expression was compared between DLBCL tissue and reactive proliferative lymph node tissue.The correlations of ZNF382 expression with the clinical features such as age,gender,primary tumor site,Ann Arbor stage,international prognostic index(IPI)score,Hans typing,B-symptoms,bone marrow infiltration,giant masses,Eastern Cooperative Oncology Group(ECOG)score,β2-microglobulin(β2-MG),serum lactate dehydrogenase(LDH),Ki67,and chemotherapy regimen of DLBCL patients were analyzed by univariate analysis;the survival curve was drawed by Kaplan Meier method,and the univariate and multivariate survival analysis were performed by log-rank tests and Cox proportional risk regression models.Results The expression level of ZNF382 in DLBCL tissue was significantly lower than that in reactive proliferative lymph node tissue(Z=-5.056,P＜0.01).The expression level of ZNF382 was correlated with IPI score,Ann Arbor stage,Hans typing,B-symptoms,bone marrow infiltration and giant masses of DLBCL patients(P＜0.05);the expression level of ZNF382 was not associated to gender,age,primary site,ECOG score,β2-MG,serum LDH,Ki67,and whether the chemotherapy regimen combined with rituximab or not of DLBCL patients(P＞0.05).Among the 57 DLBCL patients,the treatment was effective in 36 patients(63.20％)and ineffective in 21 patients(36.80％);the expression level of ZNF382 in tumor tissue of DLBCL patients with effective treatment was significantly higher than that of DLBCL patients with ineffective treatment(Z=-2.895,P＜0.05).The 2-year event free survival rate of DLBCL patients in the ZNF382 high expression group was significantly higher than that in the ZNF382 low expression group(x2=17.955,P＜0.001).The results of univariate survival analysis showed that female,primary lymph nodes,B-symptoms,bone marrow infiltration,giant masses,IPI score≥3,elevated β2-MG,Ki67＞70％,non-germinal center B-cell-like lymphoma,Ann Arbor stageⅢ-Ⅳ and low expression of ZNF382 were risk factors for poor prognosis in DLBCL patients(P＜0.05).The results of multivariate analysis showed that primary lymph nodes,Ann Arbor stage Ⅲ-Ⅳ and low expression of ZNF382 were independent influencing factors for poor prognosis in DLBCL patients(P＜0.05).Conclusion ZNF382 protein is low expressed in the tumor tissues of DLBCL patients,which is closely related to the occurrence,development and prognosis of DLBCL;and it can be used as an indicator for evaluating the prognosis of DLBCL.

Purpose/Significance Combined with flipped classroom and project-driven teaching mode,the curriculum reform is ex-plored to improve teaching effect,stimulate students to learn independently and participate deeply in class.Method/Process Taking the teaching of hospital information system course as an example,guided by the flipped classroom concept and combined with the project-driven method,the paper puts forward the reform plan of teaching design and applies it to the actual teaching process.Result/Conclusion The satisfaction degree of the students is higher,the initiative of students to study independently is improved,and the teaching quality is enhanced.

Objective:To investigate the effect of rapamycin (Rapa) on apoptosis of acute myeloid leukemia THP-1 cells induced by idarubicin (IDA) and its molecular mechanism.Methods:The THP-1 cells were treated with 10, 20, 40 and 80 nmol/L Rapa for 1 h, and the cells without Rapa treatment were set up. Western blot was used to detect the conversion of autophagy marker LC3 protein in THP-1 cells (the ratio of LC3Ⅱ/LC3Ⅰ), flow cytometry was used to detect the apoptotic rate, and the pretreatment concentration of Rapa was determined. THP-1 cells were treated with different concentrations of IDA for 24 h, the cell proliferation inhibition rate of IDA for THP-1 cells was detected by CCK-8 method, and the half maximal inhibitory concentration ( IC50) was calculated. THP-1 cells with or without Rapa treatment were treated by IDA with the concentration of lower than IC50 for 24 h, CCK-8 method was used to detect cell proliferation inhibition rate, flow cytometry was used to detect cell apoptosis, real-time fluorescent quantitative polymerase chain reaction was used to detect the expression changes of autophagy-related genes Beclin-1, LC3 and p62, and Western blot was used to detect the conversion of autophagy marker LC3 protein. Results:The ratio of LC3Ⅱ/LC3Ⅰ in THP-1 cells treated by 20 nmol/L Rapa was higher than that in the untreated cells ( P=0.002 4). The apoptotic rate in THP-1 cells treated by 80 nmol/L Rapa was higher than that in the untreated cells ( P=0.007 3). According to the results of Western blot and flow cytometry, 20 nmol/L Rapa was selected as the pretreatment concentration. The IC50 of IDA for THP-1 cells treated with IDA for 24 h was 59.874 nmol/L. After treated with 50 nmol/L IDA for 24 h, the proliferation inhibitory [(69.67±5.03)% vs. (41.67±3.51)%] and apoptotic rates [(74.35±4.83)% vs. (41.25±5.24)%] in THP-1 cells pretreated by Rapa were higher than those in the unpretreated cells (both P<0.05); the Beclin-1 and LC3 mRNA expression levels and the ratio of LC3Ⅱ/LC3Ⅰ in THP-1 cells pretreated by Rapa were higher than those in the unpretreated cells, and the expression of p62 mRNA was lower than that in the unpretreated cells (all P<0.05). Conclusion:Rapa can enhance the apoptosis of THP-1 cells induced by a relative low dose of IDA, which may be achieved through inducing excessive autophagy in THP-1 cells.

Objective:To explore the expression of Fbxw7 protein and its clinical significance in diffuse large B-cell lymphoma (DLBCL), and to provide a basis for prognostic judgement and searching the new therapeutic targets of DLBCL.Methods:A total of 72 patients with newly diagnosed DLBCL who received immunohistochemical detection of c-myc protein from January 2011 to September 2017 in Cancer Hospital Affilicoted to Zhengzhou University were enrolled. The paraffin-embedded specimens after lymph node biopsy and the clinical data of patients were also collected. At the same time, 22 samples of lymph node reactive hyperplasia were selected as the control group. Immunohistochemical method was used to detect the expression of Fbxw7 protein in DLBCL tissues and control tissues. The relationship between the expression of Fbxw7 protein and c-myc protein, the association of Fbxw7 protein expression with DLBCL patients' clinicopathological characteristics, efficacy and prognosis were analyzed.Results:The positive rate of Fbxw7 protein in DLBCL tissues was lower than that in control tissues, and the difference was statistically significant [63.89% (46/72) vs. 86.36% (19/22), χ 2 = 3.990, P = 0.046]. Among DLBCL patients, the positive rate of Fbxw7 protein in non-germinal center B cell (non-GCB) group was lower than that in germinal center B cell (GCB) group, and the difference was statistically significant [48.15% (13/27) vs. 73.33% (33/45), χ 2 = 4.639, P = 0.031]. There were no statistically significant differences in the positive rate of Fbxw7 protein among patients with different age, gender, neoplasm staging, international prognostic index (IPI) scores, B symptom, Eastern Cooperative Oncology Group (ECOG) score, lactate dehydrogenase (LDH) level, β 2 microglobulin level, and therapeutic efficacy after initial treatment (all P > 0.05). In DLBCL tissues, the expression of Fbxw7 and c-myc protein was negatively correlated ( r = -0.255, P = 0.031). The 3-year overall survival (OS) rate and 3-year progression-free survival (PFS) rate (88.3% and 82.0%) of the Fbxw7 positive group were higher than those of the Fbxw7 negative group (70.2% and 60.1%). Cox multivariate analysis showed that the down-regulation of Fbxw7 protein expression was an independent risk factor affecting OS and PFS in DLBCL patients ( HR = 3.656, 95% CI 1.055-12.674, P = 0.041; HR = 2.897, 95% CI 1.092-7.688, P = 0.033). Conclusions:The expression of Fbxw7 protein and c-myc protein in DLBCL patients is negatively correlated. Fbxw7 protein is down-regulated in DLBCL, and it is more obvious in non-GCB subtype. The down-regulated expression of Fbxw7 protein is related to the poor prognosis of DLBCL, and Fbxw7 may become a new therapeutic target of DLBCL.