Value of glycosylated hemoglobin A1c and apolipoprotein A-1 ratio on predicting outcome of patients with acute coronary syndrome / 中华心血管病杂志

Objective: To investigate the predictive value of glycosylated hemoglobin A1c/apolipoprotein A-1 (HbA1c/ApoA-1) ratio for major adverse cardiovascular events (MACEs) in patients with acute coronary syndrome (ACS). Methods: The present study is a retrospective cohort study. ACS patients who were hospitalized and underwent coronary angiography at Beijing Hospital from March 2017 to March 2019 were enrolled. Baseline information such as sex, age, previous history, Gensini score, HbA1c and ApoA-1 were analyzed. Patients were divided into two groups according to presence or absence of MACEs and the difference on HbA1c/ApoA-1 ratio was compared between the two groups. According to the tertiles of HbA1c/ApoA-1 levels, patients were divided into high (5.87-16.12), medium (4.50-5.83) and low (2.11-4.48) HbA1c/ApoA-1 groups. Cox proportional risk model was used to evaluate the differences in MACEs and all-cause mortality among the three groups. Kaplan-Meier survival analysis was used to compare the differences of MACEs between the various HbA1c/ApoA-1 groups. Results: A total of 366 ACS patients were included in this study. The mean age of the patients was (65.9±10.3) years. There were 59 MACEs and 10 all-cause deaths during the mean of (22.3±4.4) months follow-up. After adjusting for age, systolic blood pressure, history of diabetes and Gensini score, the incidence of MACEs was 2.45 times higher in the high HbA1c/ApoA-1 group than in the low HbA1c/ApoA-1 group (95%CI 1.16-5.18, P=0.019). There was no significant difference in all-cause mortality between the high and low HbA1c/ApoA-1 groups (P=1.000). Kaplan-Meier survival analysis showed that patients in the high HbA1c/ApoA-1 group had the highest risk of MACEs, while patients in the low HbA1c/ApoA-1 group had the lowest risk of MACEs (P<0.01). Spearman rank correlation analysis showed that HbA1/ApoA-1 ratio was positively correlated with Gensini score in ACS patients (r=0.274, P<0.01). Conclusion: High HbA1c/ApoA-1 ratio was an independent risk factor for MACEs in ACS patients. Patients with high HbA1c/ApoA-1 ratio had more severe coronary artery disease lesions. HbA1c/ApoA-1 ratio may be used as a potential risk stratification biomarker for ACS patients, it might be useful for the early identification of high-risk population and for predicting the incidence of MACEs among ACS patients.

Research advances on the mechanism of Wnt/β-catenin signaling pathway in body surface wound healing / 中华烧伤杂志

Wound healing is a slow and complex biological process, including inflammatory reaction, cell proliferation, cell differentiation, cell migration, angiogenesis, extracellular matrix deposition, tissue remodeling, and so on. Wnt signaling pathway can be divided into classical pathway and non-classical pathway. Wnt classical pathway, also known as Wnt/β-catenin signaling pathway, plays an important role in cell differentiation, cell migration, and maintenance of tissue homeostasis. Many inflammatory factors and growth factors are involved in the upstream regulation of this pathway. The activation of Wnt/β-catenin signaling pathway plays an important role in the occurrence, development, regeneration, repair and related treatment of skin wounds. This article review the relationship between Wnt/β-catenin signaling pathway and wound healing, meanwhile summarizes its effects on important processes of wound healing, such as inflammation, cell proliferation, angiogenesis, hair follicle regeneration, and skin fibrosis, as well as the role of inhibitors of Wnt signaling pathway in wound healing.

CXCL5 inhibits tumor immune of lung cancer via modulating PD1/PD-L1 signaling / 中华肿瘤杂志

Objective: To investigate the role of CXCL5 in tumor immune of lung cancer and to explore the potential molecular mechanisms. Methods: A total of 62 cases of patients with lung cancer admitted in the First Affiliated Hospital of Henan University from May 2018 to December 2019 were recruited as study object. Another 20 cases of patients with pulmonary infectious diseases and 20 cases of healthy control were selected as control. Enzyme-linked immunosorbent assay (ELISA) was used to determine serum levels of CXCL5 in patients with lung cancer, pulmonary infectious diseases and healthy control. Immunohistochemical staining (IHC) was used to detect the expressions of CXCL5 and PD-1/PD-L1 in tumor and paracarcinoma tissues of patients with lung cancer. Pearson correlation analysis was used to evaluate the correlation between CXCL5 and PD-1 in tumor and paracarcinoma tissues of patients with lung cancer. Lewis cells either expressing CXCL5 or vector plasmids were used to establish C57BL/6J mice model of lung cancer, and all mice were then divided into vehicle and PD-1 antibody treatment groups, 10 mice for each group. The mice survival and tumor growth curves were recorded. IHC was used to evaluate the expressions of CXCL5, PD-1 as well as the proportions of CD8(+) T and Treg cells in xenograft tumor tissues. Results: In patients with lung cancer, the serum level of CXCL5 [(351.7±51.5) ng/L] was significant higher than that in patients with pulmonary infectious diseases and healthy control [(124.7±23.4) ng/L, P<0.001]. The expression levels of CXCL5 (0.136±0.034), CXCR2 (0.255±0.050), PD-1 (0.054±0.012) and PD-L1 (0.350±0.084) in tumor were significant higher than those in paracarcinoma normal tissues [(0.074±0.022), (0.112±0.023), (0.041±0.007) and (0.270±0.043) respectively, P<0.001]. CXCL5 was significant positively correlated with PD-1 in tumor tissues of lung cancer (r=0.643, P<0.001), but not correlated with PD-1 in paracarcinoma tissues(r=0.088, P=0.496). The vector control group, CXCL5 overexpression group, vector control + anti-PD-1 antibody treatment group and CXCL5 overexpression + anti-PD-1 antibody treatment group all successfully formed tumors in mice, while CXCL5 overexpression increased the tumor growth significantly (P<0.01), which was abrogated by the treatment of anti-PD-1 antibody. CXCL5 overexpression decreased the mice survival time significantly (P<0.01), this effect was also abrogated by the treatment of anti-PD-1 antibody. The proportion of CD8(+) T cells in CXCL5 overexpression group [(10.40±2.00)%] was significant lower than that in vector control group [(21.20±3.30)%, P=0.002]. The proportion of CD4(+) Foxp3(+) Treg cells in CXCL5 overexpression group [(38.40±3.70)%] was significant higher than that in vector control group [(23.30±2.25)%, P<0.001]. After the treatment of anti-PD-1 antibody, no significant difference were observed for the proportion of CD8(+) T cells [(34.10±5.00)% and (33.40±4.00)% respectively] and Treg cells [(14.70±3.50)% and (14.50±3.30)% respectively] in xenograft tumor tissues between CXCL5 overexpression+ anti-PD-1 antibody treatment group and vector control + anti-PD-1 antibody treatment group (P>0.05). Conclusion: The expressions of CXCL5 and PD-1/PD-L1 are all increased significantly in the tumor tissues of patients with lung cancer, CXCL5 may inhibit tumor immune of lung cancer via modulating PD-1/PD-L1 signaling.

CIK cells acquired multidrug resistance and maintained cytotoxic activity to tumor cells after mdr1 gene transfection / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate whether the cytokine-induced killer (CIK) cells could acquire multidrug resistance and maintain the original cytotoxic activity after multidrug resistance (mdr1) genes transfection.</p><p><b>METHODS</b>CIK cells were generated from peripheral blood cultured with IFN-gamma, CD(3) monoclonal antibody, IL-2, IL-1 and transfected with a plasmid (pHamdr) containing human mdr1 gene via electroporation. RT-PCR method was used to assay mRNA expression of mdr1 gene in transfected CIK cells, flow cytometry with anti-P-gp monoclonal antibody to detect P-glycoprotein (P-gp) expression on CIK cells membrane, and MTT assay to compare both the multidrug resistance to doxorubicin and colchicines and cytotoxic activity to human mammary cancer cell line MCF7 between transfected and non-transfected CIK cells.</p><p><b>RESULTS</b>mdr1 expression was detected in the transfected CIK cells. There was a strong expression of P-gp on the transfected CIK cells and the percentages of P-gp positive cells were 21% - 37% (average 27%). The IC(50) of transfected CIK cells to doxorubicin was 22.3 - 45.8 times and 6.7 - 11.35 times to colchicines of those of non-transfected CIK cells. The cytotoxic activity to MCF7 remained unchanged (P > 0.05).</p><p><b>CONCLUSION</b>It demonstrated that CIK cells transfected with mdr1 gene via electroporation could express multidrug resistance successfully without changes of cytotoxic activity.</p>