The incomplete degradation of tumour cells by macrophages (Mϕ) is a contributing factor to tumour progression and metastasis, and the degradation function of Mϕ is mediated through phagosomes and lysosomes. In our preliminary experiments, we found that overactivation of NADPH oxidase 2 (NOX2) reduced the ability of Mϕ to degrade engulfed tumour cells. Above this, we screened out liquiritin from Glycyrrhiza uralensis Fisch, which can significantly inhibit NOX2 activity and inhibit tumours, to elucidate that suppressing NOX2 can enhance the ability of Mϕ to degrade tumour cells. We found that the tumour environment could activate the NOX2 activity in Mϕ phagosomes, causing Mϕ to produce excessive reactive oxygen species (ROS), thus prohibiting the formation of phagolysosomes before degradation. Conversely, inhibiting NOX2 in Mϕ by liquiritin can reduce ROS and promote phagosome-lysosome fusion, therefore improving the enzymatic degradation of tumour cells after phagocytosis, and subsequently promote T cell activity by presenting antigens. We further confirmed that liquiritin down-regulated the expression of the NOX2 specific membrane component protein gp91 phox, blocking its binding to the NOX2 cytoplasmic component proteins p67 phox and p47 phox, thereby inhibiting the activity of NOX2. This study elucidates the specific mechanism by which Mϕ cannot degrade tumour cells after phagocytosis, and indicates that liquiritin can promote the ability of Mϕ to degrade tumour cells by suppressing NOX2.

Objective To investigate the protective effect and mechanism of Danshen Tongluo Jiedu Decoction medicated serum for hypoxia/reoxygenation rat myocardial microvascular endothelial cells(CMECs)by regulating MALAT1.Methods Rats CMECs cells were cultured in vitro to establish a model of hypoxia/reoxygenation damaged cells,and were transfected overexpressing/silencing blank MALAT1 slow virus,cells were divided into overexpressed blank + TCM group,overexpressed MALAT1 + TCM group,overexpressed MALAT1 group,silenced blank + TCM group,silenced MALAT1 group,and silenced MALAT1 + TCM group.They were cultured with corresponding serum separately.Beclin-1 protein expression was detected by immunofluorescence method,and SRPK1,SRSF1,VEGF and Bax protein expressions were detected by Western blot,MALAT1,SRPK1 and SRSF1 mRNA expressions were detected by RT-PCR.Results Compared with the overexpressed blank + TCM group,Beclin-1 protein expression increased in the overexpressed MALAT1 + TCM group,the protein expressions of SRPK1,SRSF1 and Bax significantly increased(P<0.05,P<0.01),VEGF protein expression significantly decreased(P<0.01),while MALAT1,SRPK1 and SRSF1 mRNA expressions significantly increased(P<0.05,P<0.01).Compared with the overexpressed MALAT1 group,the protein expression of Beclin-1 in overexpressed MALAT1 + TCM group decreased,the expressions of SRPK1,SRSF1 and Bax protein significantly decreased(P<0.01,P<0.05),the expression of VEGF protein significantly increased(P<0.01),the mRNA expressions of MALAT1,SRPK1 and SRSF1 significantly decreased(P<0.05).Compared with the silenced blank + TCM group,the protein expression of Beclin-1 in silenced MALAT1 + TCM group decreased,the expressions of SRPK1,SRSF1 and Bax protein significantly decreased(P<0.01),while the expression of VEGF protein significantly increased(P<0.01),the mRNA expressions of MALAT1,SRPK1 and SRSF1 significantly decreased(P<0.01).Compared with the silenced MALAT1 group,the protein expression of Beclin-1 in silenced MALAT1 + TCM group decreased,the expressions of SRPK1,SRSF1 and Bax protein significantly decreased(P<0.05),the expression of VEGF protein significantly increased(P<0.01),the mRNA expressions of MALAT1,SRPK1 and SRSF1 significantly decreased(P<0.01,P<0.05).Conclusion Upregulation of MALAT1 expression can promote autophagy in hypoxia/reoxygenation model CMECs,while Danshen Tongluo Jiedu Decoction medicated serum can inhibit MALAT1 expression,thus inhibiting autophagy and promoting angiogenesis,and the mechanism may be related to the downregulation of SRPK1 and SRSF1 expressions.

Objective: To examine the association of hypertension onset age with diabetes, so as to provide insights into reducing the the risk of cardiovascular events. Methods: Permanent residents aged 35 to 75 years were selected through the program of early screening and comprehensive intervention for the high-risk cardiovascular disease population in Changning District and Baoshan District, Shanghai Municipality from 2016 to 2020. Demographic information, disease history, hypertension onset age, blood pressure and fasting blood glucose were collected through questionnaire surveys, physical examination and laboratory tests. The residents were divided into four groups based on the onset age of hypertension: <45, 45-<55, 55-<65 and ≥65 years old, and the residents with normal blood pressure were selected as control. The association of hypertension onset age with prediabetes and diabetes were identified using a multivariable logistic regression model. Results: A total of 25 228 residents were recruited, including 8 753 males (34.70%) and 16 475 females (65.30%). The prevalence of hypertension was 43.80%. There were 1 779, 3 274, 3 781 and 2 217 cases with hypertension onset age of <45, 45-<55, 55-<65 and ≥65 years old, respectively, and 14 177 residents with normal blood pressure. The prevalence of prediabetes and diabetes were 24.01% and 11.29%, respectively. Multivariable logistic regression analysis showed that after adjusting for confounding factors such as gender, marital status and educational level, compared with the normal blood pressure group, the risk of prediabetes was higher in the hypertension onset age groups of <45 (OR=1.345, 95%CI: 1.164-1.553), 45-<55 (OR=1.365, 95%CI: 1.212-1.536) and 55-<65 years old (OR=1.376, 95%CI: 1.239-1.527), and the risk of diabetes was higher in the hypertension onset age groups of <45 (OR=2.302, 95%CI: 1.906-2.775), 45-<55 (OR=2.349, 95%CI: 2.016-2.734), 55-<65 (OR=1.909, 95%CI: 1.667-2.184) and ≥65 years old (OR=1.315, 95%CI: 1.131-1.526). Conclusion There are statistically significant associations between hypertension onset age with prediabetes and diabetes.

Objective : To examine the association between prediabetes and the risk of cancer, so as to provide insights into precision cancer prevention. Methods: Based on the project of Early Screening and Comprehensive Interventions among Population at A High Risk of Cardiovascular Diseases in Changning District, Shanghai Municipality, baseline data were captured from permanent community residents at ages of 35 to 75 years from 2016 to 2019, including demographics, physical examinations, previous medical history and used of medications. The development of cancers was used as a outcome measure, and the follow-up was terminated by May 2021. The development of cancer was collected through the Changning Cancer Registration System, and the association between prediabetes and the risk of cancer was examined using a multivariable logistic regression model. Results: A total of 9 503 participants were finally included, with a mean age of (57.12±10.89) years. The participants included 2 167 cases with prediabetes (22.80%) and 7 336 individuals with normal glucose (77.20%), and included 3 713 men (39.07%) and 5 790 women (60.93%). A total of 114 new cases with cancers were diagnosed until the final follow-up, including 37 cases among prediabetic patients (1.71%) and 77 cases among participants with normal blood glucose (1.05%). Multivariable logistic regression analysis showed that after adjustment for age, gender, marital status, educational level, family annual income, smoking, alcohol consumption, body mass index, hypertension, administration of antihypertensive agents, dyslipidemia, administration of lipid-lowering agents and medical history of cardio-cerebrovascular diseases, a higher risk of cancers was detected among prediabetic patients than among participants with normal blood glucose (OR=1.528, 95%CI: 1.025-2.277), and prediabetes had no significant interactions with age, gender, smoking or alcohol consumption (all P>0.05). Conclusion Prediabetes is statistically associated with the risk of cancer.

Objective To investigate the effect of phenformin combined with hexokinase inhibitor 2-deoxyglucose (2-DG) on the treatment of triple-negative breast cancer cell lines 4T1 and MDA-MB-231. Methods Following treatment with phenformin, 2-DG or phenformin combined with 2-DG on 4T1 and MDA-MB-231 cells for 48 h, the cell proliferation in each group was detected by SRB and the apoptosis of cells was detected by flow cytometry. The concentration of glucose and lactic acid in cell culture supernatant was detected by ELISA. The activity of mitochondrial respiratory chain complex Ⅰ was detected by FlexStation3 and the mitochondrial oxygen consumption (OCR) was assayed with the Seahorse X Fe Analyzer. Results The hexokinase expression (4.6±0.17,3.73±0.21), glucose consumption (356±31，397±42) μg/10⁵ cells , Lactic acid concentration (5.59±0.52, 7.83±0.78) μmol/L in the supernatant of 4T1 and MDA-MB-231 cells in Phenformin group were higher than that in control group ( 1±0.15，1±0.12 ) , ( 289±25，301±32) μg/10⁵cells , ( 2.37±0.18，4.01±0.45) μmol/L (P < 0.01). Even if the dose was reduced by 90%, the cell viability of phenformin combined with 2-DG group (64.63±2.28, 51.97±2.29) % was still higher than that of phenformin group (86.70±1.83, 85.53±1.46) % (P<0.001). The combination of the two drugs significantly promoted the apoptosis of 4T1 and MDA-MB-231. In addition, compared with the phenformin group (5.59±0.52, 7.83±0.78) μmol/L, the phenformin combined with 2-DG group (3.46±0.37, 5.18±0.62) μmol/L cell lactic acid production also greatly reduced (P<0.01). Compared with the phenformin or 2-DG single-drug group, the phenformin combined with 2-DG group can significantly inhibit the growth rate of tumors in tumor-bearing mice (P<0.01). The median survival time of tumor-bearing mice in the phenformin combined with 2-DG group was 72.5 d, which was higher than that in the phenformin group 57 d and 2-DG group 55.5 d (P<0.01). Conclusion Hexokinase inhibitor 2-DG significantly enhances the therapeutic effects of phenformin on triple-negative breast cancer cells.

OBJECTIVE To investigate the resistance of Staphylococcus to erythromycin and clindamycin and detect the percentage and gene for inducible resistance in Tai'an.METHODS The susceptibilities of Staphylococcus to erythromycin and clindamycin were examined by Kirby-Bauer disc agar diffusion test and the inducible erythromycin resistance to clindamycin was checked by D-test according to the standards of NCCLS,and the resistance genes msrA,Vgb,sat4,ermA,ermB and ermC were detected by using PCR technology.RESULTS Among the 326 strains,162(44.12%)were all resistant to erythromycin and clindamycin;68(20.86%)were resistant to erythromycin and sensitive to clindamycin but they were positive in D-test;42(12.88%)were resistant to erythromycin and sensitive to clindamycin but they were negative in D-test.The rates of inducible resistance of MRSA,MSSA,MRCNS and MSCNS to clindamycin were 40.00%,56.25%,63.38% and 66.67%,respectively among the Staphylococcus which were resistant to erythromycin and sensitive to clindamycin.The gene ermC was the main one for inducible erythromycin resistance to clindamycin.The percentage of gene ermC was 85.29% and that of ermC and sat4 either was 7.35%;all the others were negative.CONCLUSIONS The rate of inducible erythromycin resistance to clindamycin in our area is relatively high,and D-test in clinical microbiology laboratory should be done so that the physicians can select the reasonable MLSB antimicrobial agents.

In the process of hepatocarcinogenesis induced by diethylnitrosamine (DENA) in rats, the hepatocellular ultrastructure and G-6-Pase reactions in hepatic nodes were observed by electron microscope. The results are as follows: As compared with normal hepatocytes, cell junctions were fewer, even disappeared in some areas and intercellular spaces were wider; in some cells, nuclear membranes invaginated into the nucleoplasms frequently, micleoli were enlarged, mitochondria appeared swollen and their cristae were scanty- and short, and depolymerized ribosomes dropped off the dilated rough endoplasmic reticulums; in some seriously diseased cells, nucleoli were enlarged, abundant free ribosomes were present, but the' other organelles were in lower differencial state. G-6-Pase reactions were positive before the 8th week of DENA induction and negative after the 12th week. These suggest the hepatocellular metabolic disturbance and low differenciation.