1.Expressions of bcl-2, programmed death-1 and programmed death ligand-1 in diffuse large B-cell lymphoma and their prognostic significances
Yahui CHEN ; Aiping LI ; Dan SHI ; Yulin HU ; Huiqiu CAO ; Tianyun MENG ; Xiaojie LI
Journal of Leukemia & Lymphoma 2020;29(4):225-231
Objective:To investigate the expressions and correlation of bcl-2, programmed death-1 (PD-1) and programmed death ligand-1(PD-L1) in diffuse large B-cell lymphoma (DLBCL) tissue specimens, and the relationship between chemotherapy efficacy and prognosis of DLBCL patients.Methods:The expressions of bcl-2, PD-1 and PD-L1 in 82 patients with DLBCL who were admitted to Chenzhou First People's Hospital of Hunan Province from May 2011 to April 2014 were detected by using immunohistochemistry, and the correlation of the expressions of bcl-2, PD-1 and PD-L1 with clinicopathological characteristics and prognosis was analyzed.Results:The positive rate of bcl-2, PD-L1 and PD-1 in cancer tissues of DLBCL patients was 53.7% (44/82), 56.1% (46/82) and 32.9% (27/82), respectively. There was a correlation between bcl-2 and PD-L1 expression ( r = 0.306, P = 0.005). Bcl-2 was highly expressed in patients with international prognosis index (IPI) score 3-4 points, non-germinal center B-cell-like (non-GCB) subtype and B symptoms (all P < 0.05); PD-1 was highly expressed in patients with IPI score 3-4 points ( P < 0.05); PD-L1 was highly expressed in patients with IPI score 3-4 points, tumor stage Ⅲ-Ⅳ, B symptoms, ≥60 years old, and non-GCB (all P < 0.05). The overall survival (OS) and progression-free survival (PFS) in bcl-2-negative group were better than those in the bcl-2-positive group, and the differences were statistically significant (both P < 0.05); OS and PFS in PD-L1-negative group were better than those in PD-L1-positive group, and the differences were statistically significant(both P < 0.01). There were no statistical differences in OS and PFS between PD-1-positive group and PD-1-negative group (both P > 0.05). OS and PFS in bcl-2 and PD-L1 co-expression group were worse than those in both negative or any negative group (all P < 0.01), and PFS in bcl-2 and PD-1 co-expression group was worse than those in both negative or any negative group ( P = 0.044). Cox multivariate analysis showed IPI score 3-4 points and B symptoms were the independent influencing factors of OS in DLBCL patients (both P < 0.01); IPI score 3-4 points, B symptoms and PD-L1-positive were the independent influencing factors of poor PFS in DLBCL patients (all P < 0.05). Conclusion:The positive expressions of bcl-2 and PD-L1 are the independent factors for the poor prognosis of DLBCL patients, which may become new targets for the treatment of DLBCL.
2.The expression and clinical significance of promyelocytic leukemia zinc finger in human peripheral blood with asthma
Xiaoting REN ; Tianyun SHI ; Na LI ; Yanchao HE ; Ling QIAN ; Jingjing FENG ; Zhoufang MEI ; Zhijun JIE
Chinese Journal of Emergency Medicine 2022;31(10):1389-1395
Objective:To investigate the expression of promyelocytic leukemia zinc finger (PLZF) in human peripheral blood with asthma and its clinical significance.Methods:Forty patients with stable asthma from May 2021 to October 2021 in the Department of Respiratory Medicine of the Shanghai Fifth People's Hospital were enrolled, and forty healthy controls were recruited in the study. The levels of cytokines in serum were measured by enzyme-linked immunosorbent assay (ELISA). Quantitative real-time PCR (qPCR) was used to detect the expression of PLZF mRNA in plasma. The level and distribution of PLZF+ cells in PBMCs were detected by flow cytometry after isolating peripheral blood mononuclear cells (PBMCs). Independent sample t test, Mann-Whitney U test, χ 2 test, ROC curve and Logistic regression were used to analyze the results with SPSS 26.0 and Graphpad Prism 7.0. A P<0.05 was considered statistically significant. Results:The levels of cytokines IFN-γ, IL-2, IL-4, TNF-α and IL-17 in human peripheral blood from the asthma group were obviously higher than those in the control group ( P<0.05), whereas there was no significant difference in the level of cytokine IL-10 between the two groups. The level of PLZF mRNA in PBMCs from the asthma group was significantly up-regulated compared to that in the control group [(3.40%±2.52%) vs. (1.23%±0.78%), P<0.05]. CD8+PLZF+ and Vβ11+PLZF+T cells in the asthma group were significantly outnumbered than those in the control group ( P<0.05). Logistic regression and ROC curve analysis showed that PLZF expression in PBMC was a risk factor for the development of asthma ( OR =3.67, AUC=0.87, P<0.05). Conclusions:The high expression of PLZF in peripheral blood may play an important role in the development of asthma, which needs to be further confirmed by large sample studies.
3.Clinical Effect of Qifu Yixin Prescription on Chronic Heart Failure in Patients with Syndrome of Heart Qi Deficiency
Zhaohui XU ; Yihang ZHONG ; Tianyun SHI ; Jiahui YANG ; Zhirui LIU ; Qiqi WAN ; Yongming LIU
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(23):98-105
ObjectiveTo explore the clinical efficacy and safety of Qifu Yixin prescription in treating chronic heart failure in the patients with the syndrome of heart Qi deficiency, so as to provide clinical evidence for the treatment of chronic heart failure with this prescription and promote the clinical application and transformation of this prescription. MethodA total of 106 chronic heart failure patients with the syndrome of heart Qi deficiency who met the criteria in Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (TCM) from September 2022 to May 2023 were selected and randomized into an observation group (53 cases) and a control group (53 cases). Both groups received routine Western medicine treatment. In addition, the observation group received Qifu Yixin prescription, while the control group received placebo. The treatment course for both groups was 12 weeks. The New York heart association (NYHA) cardiac function grading, N-terminal pro-B-type natriuretic peptide (NT-proBNP), soluble growth-stimulating expression gene 2 (sST2), left ventricular ejection fraction (LVEF), the ratio of early diastolic maximum mitral flow velocity (E) to early diastolic mitral annular motion velocity (e') (E/e'), left ventricular end diastolic diameter (LVEDD), TCM syndrome scores, 6-minute walking test (6MWT), Minnesota Living with Heart Failure Questionnaire (MLHFQ), and Kansas City Cardiomyopathy Questionnaire (KCCQ) were determined before and after treatment. ResultFinally, 102 patients were included for analysis, including 51 patients in the observation group and 51 patients in the control group. After treatment, 42 patients in the observation group showed improved cardiac function grading, with a total response rate of 82.35%, and 32 patients in the control group showed improved cardiac function grading, with a total response rate of 62.75%. The total response rate regarding the cardiac function in the observation group was higher than that in the control group (χ2=4.923, P<0.05). The observation group outperformed the control group in lowering the NT-proBNP level, elevating LVEF, decreasing the E/e' ratio (P<0.05), reducing LVEDD and sST2 levels, and recovering TCM syndrome score, 6MWT score, MLHFQ score, and KCCQ score (P<0.05). None of the safety indexes in the two groups showed abnormal values before and after treatment, and no serious adverse reaction was observed. ConclusionQifu Yixin prescription can improve the heart function, exercise tolerance, and quality of life and alleviate the TCM syndrome of the chronic heart failure patients with the syndrome of heart Qi deficiency by inhibiting myocardial fibrosis.
4.Discovery and identification of EIF2AK2 as a direct key target of berberine for anti-inflammatory effects.
Wei WEI ; Qingxuan ZENG ; Yan WANG ; Xixi GUO ; Tianyun FAN ; Yinghong LI ; Hongbin DENG ; Liping ZHAO ; Xintong ZHANG ; Yonghua LIU ; Yulong SHI ; Jingyang ZHU ; Xican MA ; Yanxiang WANG ; Jiandong JIANG ; Danqing SONG
Acta Pharmaceutica Sinica B 2023;13(5):2138-2151
Using chemoproteomic techniques, we first identified EIF2AK2, eEF1A1, PRDX3 and VPS4B as direct targets of berberine (BBR) for its synergistically anti-inflammatory effects. Of them, BBR has the strongest affinity with EIF2AK2 via two ionic bonds, and regulates several key inflammatory pathways through EIF2AK2, indicating the dominant role of EIF2AK2. Also, BBR could subtly inhibit the dimerization of EIF2AK2, rather than its enzyme activity, to selectively modulate its downstream pathways including JNK, NF-κB, AKT and NLRP3, with an advantage of good safety profile. In EIF2AK2 gene knockdown mice, the inhibitory IL-1β, IL-6, IL-18 and TNF-α secretion of BBR was obviously attenuated, confirming an EIF2AK2-dependent anti-inflammatory efficacy. The results highlight the BBR's network mechanism on anti-inflammatory effects in which EIF2AK2 is a key target, and inhibition of EIF2AK2 dimerization has a potential to be a therapeutic strategy against inflammation-related disorders.