Objective To investigate the expressions of extracellular matrix metalloproteinase inducer(EMMPRIN),matrix metalloproteinase-9(MMP-9),lysine demethylase 6B(KDM6B)proteins and their correlation with clinicopathologic features in invasive breast cancer,and analyze the correlation among the three proteins and their value in pathological diagnosis of invasive breast cancer.Methods The surgical biopsy specimens of 124 patients with invasive breast cancer who were admitted to the Department of Pathology,the Fifth Clinical Medical College of Henan University of Chinese Medicine/People's Hospital of Zhengzhou from January 2014 to December 2017 were selected as research subjects,and 20 low-grade intraductal carcinoma tissue specimens,27 high-grade intraductal carcinoma tissue specimens,and 22 adjacent tissue specimens＞1 cm away from the invasive breast cancer were selected as controls.The expressions of EMMPRIN,MMP-9 and KDM6B proteins in cancer-adjacent tissues,low-grade intraductal carcinoma tissues,high-grade intraductal carcinoma tissues and invasive breast cancer tissues were detected by immunohistochemistry.The relationship between the relative expressions of EMMPRIN,MMP-9 and KDM6B proteins and clinicopathologic features of invasive breast cancer was analyzed,Spearman correlation analysis was used to evaluate the correlation of EMMPRIN,MMP-9 and KDM6B proteins in breast cancer tissues,and receiver operating characteristic(ROC)curve was adopted to evaluate the diagnostic value of EMMPRIN,MMP-9 and KDM6B for invasive breast cancer.Results The relative expressions of EMMPRIN and MMP-9 proteins in high-grade intraductal carcinoma and invasive breast cancer tissues were significantly higher those in cancer-adjacent tissues and low-grade intraductal carcinoma tissues,and the relative expression of KDM6B protein was significantly lower than those in cancer-adjacent tissues and low-grade intraductal carcinoma tissues(P＜0.05);the relative expressions of EMMPRIN and MMP-9 proteins in invasive breast cancer tissues were significantly higher those in high-grade intraductal carcinoma tissues,and the relative expression of KDM6B protein was significantly lower than that in high-grade intraductal carcinoma tissues(P＜0.05);there was no statistically significant difference in the relative expressions of EMMPRIN,MMP-9 and KDM6B proteins between cancer-adjacent tissues and low-grade intraductal carcinoma tissues(P＞0.05).The relative expressions of EMMPRIN and KDM6B proteins were not related to the age,tumor location and tumor diameter of patients with invasive breast cancer(P＞0.05),and the relative expression of MMP-9 protein was not related to the age and tumor location of patients with invasive breast cancer(P＞0.05).Relative expressions of EMMPRIN,MMP-9 and KDM6B proteins were correlated with WHO grading,lymph node metastasis,and tumor,node and metastasis(TNM)staging of invasive breast cancer(P＜0.05),and the relative expression of MMP-9 protein was correlated with the tumor diameter(P＜0.05).In the WHO grades Ⅰ,Ⅱ,and Ⅲ of invasive breast cancer,the relative expressions of EMMPRIN and MMP-9 proteins increased sequentially,while the relative expression of KDM6B protein decreased sequentially(P＜0.05);the relative expressions of EMMPRIN and MMP-9 proteins in the lymph node metastasis group were significantly higher than those in the non-lymph node metastasis group,and the relative expression of KDM6B protein was significantly lower than that in the non-lymph node metastasis group(P＜0.05);the relative expressions of EMMPRIN and MMP-9 proteins in TNM stages Ⅲ-Ⅳ were significantly higher than those in stages Ⅰ-Ⅱ(P＜0.05),while the relative expression of KDM6B protein was significantly lower than that in stages Ⅰ-Ⅱ(P＜0.05).In the group of invasive breast cancer with diameter≤2 cm,2 to 5 cm,and＞5 cm,the relative expression of MMP-9 protein increased sequentially(P＜0.05).Spearman correlation analysis showed that the expression of EMMPRIN was positively correlated with MMP-9 protein in invasive breast cancer tissues(r=0.990,P=0.000),the expression of EMMPRIN was negatively correlated with KDM6B protein(r=-0.606,P=0.000),and the expression of MMP-9 was negatively correlated with KDM6B protein(r=-0.612,P=0.000).ROC curve analysis showed that the area under the curve(AUC)of EMMPRIN protein for diagnosing invasive breast cancer was 0.875[95％confidence interval(CI):0.823-0.926,P＜0.05],with an optimal threshold of 10.043,sensitivity of 79.0％,and specificity of 76.8％;the AUC of MMP-9 protein in diagnosing invasive breast cancer was 0.863(95％CI:0.808-0.917,P＜0.05),with an optimal threshold of 10.070,sensitivity of 74.2％,and specificity of 76.8％;the AUC of KDM6B protein in diagnosing invasive breast cancer was 0.267(95％CI:0.196-0.338,P＜0.05),with an optimal threshold of 11.003,sensitivity of 71.0％,and specificity of 98.6％.Conclusion EMMPRIN,MMP-9 and KDM6B are related to the occurrence and development of invasive breast cancer.Detection of the expressions of EMMPRIN,MMP-9 and KDM6B is helpful to the pathological diagnosis of invasive breast cancer and clinical judgment of invasion and metastasis of breast cancer.

Objective: To analyze the prevalence of comorbidity of spinal curvature abnormality and malnutrition among primary and secondary school students aged 10-18 years in Tianjin in 2023, so as to provide scientific basis for the combined prevention of common diseases and multiple diseases among students and the construction of school health system. Methods: In September to October 2023, 31 884 primary and secondary school students aged 10 to 18 years in Tianjin were selected using stratified cluster random sampling. Abnormal spinal curvature in children and adolescents was assessed by Sereening of Spinal Curvature Abnormality of Children and Adolescents, while stunting, wasting, overweight, and obesity were determined according to the Screening for Malnutrition among Schoolage Children and Adolescents and Screening for Overweight and Obesity among Schoolage Children and Adolescents. The χ2 test was used to compare betweengroup differences in coprevalence, and multiple Logistic regression models were used to analyze the risk of different comorbidity types in different clusters. Results: The coprevalence of spinal curvature abnormality and malnutrition among primary and secondary school students in Tianjin was 1.6%, which was higher for girls than boys (1.8%, 1.4%), higher (2.5%) for senior high schools than for junior high schools and elementary schools (2.0%, 0.5%), and higher in rural than in urban areas (2.1%, 1.1%) (χ2=9.45, 141.92, 46.94, P<0.05). Multiple Logistic regression models showed that junior high school girls had a higher risk of incorrect posture comorbid with stunting and wasting (OR=4.52, 95%CI=1.84-11.06) and incorrect posture comorbid with overweight and obesity (OR=2.67, 95%CI=1.74-4.10) than boys, and that scoliosis/sagittal spinal abnormality comorbid with stunting and wasting (OR=0.10, 95%CI=0.02-0.44) risk was lower than that of boys, senior high school girls had a lower risk of scoliosis/sagittal spinal abnormality comorbid with overweight and obesity (OR=0.27, 95%CI=0.11-0.66) (P<0.05). Conclusions The coprevalence of spinal curvature abnormality and malnutrition is specific among primary and secondary school students in Tianjin, and the comorbidity type varies by gender and education stage. There is a need to increase prevention and control of spinal curvature abnormalities in school health working, intensive screening of key populations, and timely intervention.

Objective To explore the effect of fluid shear stress on the expression of glucose regulatory protein 78(GRP78)and C/EBP homologous protein(CHOP)in human umbilical vein endothelial cells(HUVECs).Methods HUVECs were used as experimental cells,and a fluid dynamics simulation experimental system was designed and constructed.Different fluid shear stresses were applied to the experimental cells by controlling the flow rate of the perfusion fluid in the experimental system.According to the fluid shear stress experienced by the experimental cells in the experimental system,they were divided into low shear stress group(group A;0.4Pa),medium shear stress group(group B;0.8 Pa)and high shear stress group(group C;1.2 Pa).Each group of HUVECs consisted of 3 cell slides,and each slide was repeatedly circulated through the perfusion solution of the experimental system for 12 h.Western blotting was used to detect the levels of GRP78 and CHOP proteins,and real-time quantitative reverse transcription polymerase chain reaction was used to determine the levels of GRP78 and CHOP and their messenger RNA(mRNA)in each group.GraphPad Prism 8.0 software was used to statistically analyze the data.Results(1)The relative expression levels of GRP78 protein in groups A,B and C were 1.33±0.46,0.93±0.34,0.64±0.30,respectively,the difference among groups was statistically significant(F=36.17,P＜0.05).The relative expression level of GRP78 protein in group A was higher than that in group B and group C(both P＜0.01),and the relative expression level of GRP78 protein in group B was higher than that in group C(P=0.0013).The relative expression levels of CHOP protein in the three groups were 1.29±0.38 in group A,0.90±0.34 in group B,and 0.59±0.29 in group C,the difference among groups was statistically significant(F=41.27,P＜0.05).The relative expression level of CHOP protein in group A was higher than that in group B and group C(both P＜0.01),and the relative expression level of CHOP protein in group B was higher than that in group C(P=0.0 004).(2)The relative expression levels of GRP78 mRNA in groups A,B,and C were 18.3±3.4,11.3±1.8,5.4±2.2,respectively,the difference among groups was statistically significant(F=189.20,P＜0.05).The relative expression level of GRP78 mRNA in group A was higher than that in group B and group C(both P＜0.01),and the relative expression level of GRP78 mRNA in group B was higher than that in group C(P＜0.01).The relative expression levels of CHOP mRNA in the three groups were 20.4±3.8 in group A,14.2±2.1 in group B,and 7.8±1.3 in group C,the difference among groups was statistically significant(F=171.80,P＜0.05).The relative expression level of CHOP mRNA in group A was higher than that in group B and group C(both P＜0.01),and the relative expression level of CHOP mRNA in group B was higher than that in group C(P＜0.01).Conclusion Low fluid shear stress may increase the protein and mRNA expression levels of GRP78 and CHOP in HUVECs.

Objective:To explore the characteristics of T lymphocyte subsets and cytokines in hyperlipidemia-induced acute pancreatitis (HLAP) and its prognostic value.Methods:This study included 184 patients with acute pancreatitis (AP) admitted to the First Affiliated Hospital of Xiamen University from January 2018 to May 2021. Based on disease etiology, there were 92 HLAP cases and 92 non-hyperlipidemia-induced AP (NHLAP) cases. Stratified by disease severity according to 2012 Atlanta classification criteria, the patients were divided into the severe subgroup (SAP) and non-severe subgroup (NSAP). Peripheral venous blood samples were taken from all patients on day 1, 3, and 5 after admission. T lymphocyte subsets were determined by flow cytometry, and cytokines were detected by flow fluorometry. The number of CD4 +% and CD8 +% and the expression of cytokines were compared by Student’s t test or Mann-Whitney U analysis. Logistic regression analyses were performed to identify risk factors for severe AP, and a receiver operating characteristic (ROC) curve was constructed to predict severe AP. Statistical significance was taken as P<0.05. Results:Compared with the NHLAP group, patients in the HLAP group had lower CD4 +%, while higher levels of IL-2 on day 1 ( P<0.05), and had also lower CD4 +%, while higher levels of IL-4, IL-6, and IL-10 on day 3 ( P<0.05). Furthermore, IL-6 and IL-10 levels of the HLAP group were significantly increased compared to the NHLAP group on day 5 ( P<0.05). IL-10 levels in the SAP subgroup were significantly higher than those in the NSAP subgroup on day 1 ( P<0.05). Compared with the NSAP subgroup, the SAP subgroup had elevated levels of IL-2, IL-4, IL-6, IL-10 and IFN-γ on day 3 (all P<0.05), and had lower CD4 +%, while increased levels of IL-6 and IL-10 on day 5 (all P<0.05). Multivariate Logistic regression analysis showed that IL-10 was an immune indicator of independent risk factor for severe AP in the HLAP group on day 1 ( OR=1.139, 95% CI: 1.038-1.251, P<0.05). Finally, ROC analysis showed that the area under the curve of IL-10 to assess HLAP with severe AP was 0.772, and the best cut-off value for predicting severe AP was 5.6 pg/mL, with a sensitivity of 83.3% and a specificity of 68.8%. Conclusions:Changes of CD4 +% and cytokines are different between the HLAP and NHLAP groups. IL-10 can be used as a predictor of early disease severity in patients with HLAP.

Anaplastic lymphoma kinase (ALK) fusion gene, as a tumor driver gene, was crucial for the occurrence and development of non-small cell lung cancer (NSCLC). Recently, targeted ALK fusion gene has become the main treatment method for ALK-positive NSCLC. The first and second generation ALK inhibitors (ALKi), such as crizotinib, ceritinib, alectinib and ensartinib have been approved in China. However, there was no guidance for the management of ALKi adverse reactions. Therefore, this "Recommendations from experts in the management of adverse reactions to ALK inhibitors (2021 version)" has been summarized, led by Lung Cancer Professional Committee of Sichuan Cancer Society and Sichuan Medical Quality Control Center for Tumor Diseases, to provide practical and feasible strategies for clinical ALKi management specification of adverse reactions.
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Carcinoma, Non-Small-Cell Lung ; Crizotinib ; Humans ; Lung Neoplasms/genetics* ; Protein Kinase Inhibitors/adverse effects* ; Receptor Protein-Tyrosine Kinases/antagonists & inhibitors*

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated proteins (Cas) system is a hotspot of gene editing and gene expression research, in which CRISPR/Cas13 system provides a new direction for RNA interference and editing. In this study, we designed and synthesized the corresponding gRNAs of CRISPR/Cas13a and CRISPR/Cas13b systems in non-homologous end joining (NHEJ) pathway, such as Ku70 and Lig4, and then detected the expression of ku70 and lig4 in HEK293T cells. The CRISPR/Cas13a system could efficiently knockdown the mRNA expression of ku70 and lig4 more than 50%, and CRISPR/Cas13b system also suppressed ku70 and lig4 about 92% and 76%, respectively. Also, CRISPR/Cas13a, b systems could down-regulate Ku70 and Lig4 proteins level to 68% and 53%, respectively. The study demonstrates that the CRISPR/Cas13 system could effectively knockdown the expression of RNA and protein in HEK293T cells, providing a new strategy for gene function and regulation research.
CRISPR-Cas Systems ; DNA Ligase ATP ; genetics ; Gene Expression Regulation ; genetics ; Gene Knockdown Techniques ; HEK293 Cells ; Humans ; Ku Autoantigen ; genetics

OBJECTIVE: To examine the expressions of JMJD3, matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) in invasive ductal breast carcinoma, their association with the clinicopathological features of the patients and the effect of JMJD3 overexpression on proliferation and MMP-2 and VEGF expressions in breast cancer cells. METHODS: The protein and mRNA expressions of JMJD3, MMP-2, and VEGF in invasive ductal breast carcinoma and paired adjacent tissues were detected by immunohistochemistry and RT-PCR, respectively, and their correlation with the clinicopathological characteristics of the patients was analyzed. Kaplan-Meier survival analysis was used to evaluate the correlation of JMJD3, MMP-2 and VEGF expression levels with the survival of the patients. In breast cancer MDA-MB-231 cells transfected with a JMJD3-expression plasmid, the expression of Ki67 was examined immunohistochemically, the cell proliferation was assessed with CCK8 assay, and the mRNA expressions of MMP-2 and VEGF were detected with RT-PCR. RESULTS: Breast cancer tissues had significantly lower JMJD3 expression and higher MMP-2 and VEGF expressions at both the mRNA and protein levels than the adjacent tissue ( CONCLUSIONS The expressions of JMJD3, MMP-2 and VEGF in invasive ductal breast carcinoma are closely correlated to tumor proliferation, invasion, metastasis and prognosis and can be used for prognostic evaluation of breast cancer.
Breast Neoplasms/genetics* ; Carcinoma, Ductal, Breast/genetics* ; Humans ; Jumonji Domain-Containing Histone Demethylases ; Lymphatic Metastasis ; Matrix Metalloproteinase 2 ; Prognosis ; Vascular Endothelial Growth Factor A

PURPOSE: Details of patients hospitalized for asthma exacerbation in mainland China are lacking. To improve disease control and reduce economic burden, a large sample survey among this patient population is indispensable. This study aimed to investigate the clinical characteristics and outcomes of such patients.METHODS: A retrospective study was conducted on patients hospitalized for asthma exacerbation in 29 hospitals of 29 regions in mainland China during the period 2013 to 2014. Demographic features, pre-admission conditions, exacerbation details, and outcomes were summarized. Risk factors for exacerbation severity were analyzed.RESULTS: There were 3,240 asthmatic patients included in this study (57.7% females, 42.3% males). Only 28.0% used daily controller medications; 1,287 (39.7%) patients were not currently on inhaled corticosteroids. Acute upper airway infection was the most common trigger of exacerbation (42.3%). Patients with severe to life-threatening exacerbation tended to have a longer disease course, a smoking history, and had comorbidities such as hypertension, chronic obstructive pulmonary disease (COPD), and food allergy. The multivariate analysis showed that smoking history, comorbidities of hypertension, COPD, and food allergy were independent risk factors for more severe exacerbation. The number of patients hospitalized for asthma exacerbation varied with seasons, peaking in March and September. Eight patients died during the study period (mortality 0.25%).CONCLUSIONS: Despite enhanced education on asthma self-management in China during recent years, few patients were using daily controller medications before the onset of their exacerbation, indicating that more educational efforts and considerations are needed. The findings of this study may improve our understanding of hospital admission for asthma exacerbation in mainland China and provide evidence for decision-making.
Adrenal Cortex Hormones ; Asthma ; China ; Comorbidity ; Disease Progression ; Education ; Female ; Food Hypersensitivity ; Hospitalization ; Humans ; Hypertension ; Inpatients ; Medication Adherence ; Mortality ; Multivariate Analysis ; Pulmonary Disease, Chronic Obstructive ; Retrospective Studies ; Risk Factors ; Seasons ; Self Care ; Smoke ; Smoking

OBJECTIVE： To provide reference for improving emergency capacity of the hospital pharmacy department in response to the novel coronavirus pneumonia （COVID-19） epidemic. METHODS ：According to the related regulations and requirements of Law of the People ’s Republic of China on the Prevention and Control of Infectious Diseases ，combined with the situation of COVID- 19 epidemic prevention and control ，and management experience of relevant hospitals ，on the basis of in-depth analysis of drug supply and quality assurance ，drug dispensing management ，provision of clinical pharmaceutical services and other related material support of hospital pharmacy department，integrated emergency management model was constructed for COVID- 19 epidemic prevention and control ，and the precautions and response measures of each link were sorted out. RESULTS ：Integruted emergency management mode for COVID-19 epidemic prevention and control in hospital pharmacy department included but was not limited to human resource management，drug and disinfection products supply management （mainly including key treatment drugs and disinfection product list formulation，control，inventory increase ，etc.）；drug dispensing management （mainly including prescription ，pharmacy window ， planning quantitative reserve ， drug return ， etc.）；clinical pharmaceutical care management （mainly including providing pharmaceutical information support ，online pharmaceutical service ，monitoring drug safety ，etc.）；personnel protection and disinfection （mainly including personnel protection ，environment and window ，equipment and container ，paper prescription disinfection，etc.）；special management of donated drugs ；prevention and control knowledge training ；pharmaceutical education and scientific research management ，etc. CONCLUSIONS ：The integrated emergency management model for epidemic prevention and control is helpful for hospital pharmacy to manage public health emergencies. During the outbreak of COVID- 19，hospital pharmacy department should start integrated emergency management mode for epidemic prevention and control ，strengthen the risk control of each link ，and play a good role in the key functional departments in the special period.

Objective To investigate the biomechanical properties of human calcaneus by finite element method. Methods Through CT scanning, Mimics, Geomagic and other software, the finite element model of calcaneus was established. The stress distribution and displacement tendency of calcaneus under normal standing and external force were analyzed. Results Under normal standing, the calcaneal stress was uniformly distributed and small. Under external force, the entire calcaneus stress increased significantly, and the stress on calcaneocuboid articular surface also obviously increased. Conclusions The analysis of the stress and strain distribution on calcaneus in neutral position under different loading, and the investigation on biomechanical properties of calcaneus and mechanism of calcaneal fracture will provide theoretical basis for clinical treatment of calcaneal fractures.