1.Preliminary study on the effect of Echinococcus multilocaris on phenotypic transformations of glucose metabolism and polarization types in macrophages
Yinhong SHEN ; Tao ZHANG ; Zihan YANG ; Yaogang ZHANG ; Dengliang HUANG ; Jing HOU ; Meiyuan TIAN ; Yanyan MA
Chinese Journal of Schistosomiasis Control 2023;35(6):590-603
Objective To investigate the effects of Echinococcus multilocularis on the phenotypic transformations of glucose metabolism, polarization types and inflammatory responses in macrophages, so as to provide insights into elucidation of echinococcosis pathogenesis. Methods Bone marrow cells were isolated from C57BL/6J mice at ages of 6 to 8 weeks, and induced into bone marrow-derived macrophages (BMDMs) with mouse macrophage colony-stimulating factor (M-CSF), which served as controls (BMDMs-M0). BMDMs-M0 induced M2 macrophages by interleukin-4 for 24 hours served as the IL-4 induction group, and BMDMs-M0 co-cultured with 2.4 ng/mL E. multilocularis cystic fluid (CF) served as the BMDM-CF co-culture group, while BMDMs-M0 co-cultured with E. multilocularis protoscolex (PSC) at a ratio of 500:1 served as the BMDM-PSC co-culture group. The types of polarization of BMDMs co-cultured with E. multilocularis CF and PSC were analyzed using flow cytometry, and the expression of macrophage markers, inflammatory factors, and glucose metabolism-related enzymes was quantified using fluorescent quantitative real-time PCR (qPCR) and Western blotting assays. Results There were significant differences among the four groups in terms of Arginase-1 (Arg1) (F = 1 457.00, P < 0.000 1), macrophages-derived C-C motif chemokine 22 (Ccl22) (F = 22 203.00, P < 0.000 1), resistin-like α (Retnla) (F = 151.90, P < 0.000 1), inducible nitric oxide synthase (iNOS) (F = 107.80, P < 0.001), hexokinase (HK) (F = 9 389.00, P < 0.000 1), pyruvate kinase (PK) (F = 641.40, P < 0.001), phosphofructokinase 1 (PFK1) (F = 43.97, P < 0.01), glucokinase (GK) (F = 432.50, P < 0.000 1), pyruvate dehydrogenase kinases1 (PDK1) (F = 737.30, P < 0.000 1), lactic dehydrogenase (LDH) (F = 3 632.00, P < 0.000 1), glucose transporter 1 (GLUT1) (F = 532.40, P < 0.000 1), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (F = 460.00, P < 0.000 1), citrate synthase (CS) (F = 5 642.00, P < 0.01), glycogen synthase1 (GYS1) (F = 273.30, P < 0.000 1), IL-6 (F = 1 823.00, P < 0.000 1), IL-10 (F = 291.70, P < 0.000 1), IL-1β (F = 986.60, P < 0.000 1), and tumor necrosis factor (TNF)-α (F = 334.80, P < 0.000 1) and transforming growth factor (TGF)-β mRNA expression (F = 163.30, P < 0.001). The proportion of M2 macrophages was significantly higher than that of M1 macrophages in the BMDM-PSC co-culture group [(22.87% ±1.48%) vs. (1.70% ±0.17%); t = 24.61, P < 0.001], and the proportion of M2 macrophages was significantly higher than that of M1 macrophages in the BMDM-CF co-culture group [(20.07% ±0.64%) vs. (1.93% ±0.25%); t = 45.73, P < 0.001]. The mRNA expression of M2 macrophages markers Arg1, Ccl22 and Retnla was significantly higher in the BMDM-CF and BMDM-PSC co-culture groups than in the control group (all P values < 0.01), and no significant difference was seen in the mRNA expression of the M1 macrophage marker iNOS among the three groups (P > 0.05), while qPCR assay quantified higher mRNA expression of key glycolytic enzymes HK, PK and PFK, as well as inflammatory factors IL-10, IL-1β, TNF-α and TGF-β in the BMDM-CF and BMDM-PSC co-culture groups than in the control group (all P values < 0.01). Western blotting assay determined higher HK, PK and PFK protein expression in the BMDM-PSC co-culture group than in the control group (all P values < 0.05), and qPCR quantified higher GLUT1, GAPDH and IL-6 mRNA expression in the BMDM-CF co-culture group than in the control group (all P values < 0.05), while higher HK, PK and PFK protein and mRNA expression (all P values < 0.01), as well as lower IL-6 and TNF-α and higher TGF-β mRNA expression (both P values < 0.05) was detected in the IL-4 induction group than in the control group. Glycolytic stress test showed no significant difference in the extracellular acidification rate (ECAR) of mouse BMDM among the control group, IL-4 induction group and BMDM-PSC co-culture group (F = 124.4, P < 0.05), and a higher ECAR was seen in the BMDM-PSC co-culture group and a lower ECAR was found in the IL-4 induction group than in the control group (both P values < 0.05). Conclusions Treatment of E. multilocularis CF or PSC mainly causes polarization of BMDM into M2 macrophages, and phenotypic transformation of glucose metabolism into high-energy and high-glycolytic metabolism, and affects inflammatory responses in BMDM.
2.QT interval prolongation caused by concomitant use of moxifloxacin hydrochloride injection and amiodarone hydrochloride for injection
Anqin ZHOU ; Min LUO ; Dengliang ZHANG ; Ting XU
Adverse Drug Reactions Journal 2020;22(1):42-43
A 75-year-old male received an IV infusion of moxifloxacin hydrochloride injection (moxifloxacin) 400 mg/d once daily for valvular heart disease complicated with heart failure and pulmonary infection. On the second day, the electrocardiogram showed that the corrected QT interval (QTc) was prolonged from 455 ms before treatment to 490 ms. On the third day, amiodarone hydrochloride for injection (amiodarone) 150 mg was given by slow intravenous injection in the early morning due to atrial fibrillation and 300 mg of amiodarone was continuously pumped at the speed of 30 mg/h at noon. In the afternoon of the 4th day, amiodarone 300 mg was given again via a pump at a speed of 30 mg/h. About 20 minutes later,the QTc was prolonged to 607 ms. On the 5th day, amiodarone was not given again, but the QTc continued to be prolonged up to 674 ms. On the 6th day, the QTc gradually returned to be within the normal range after discontinuation of moxifloxacin. The prolongation of QT interval in the patient was considered to be associated with moxifloxacin and amiodarone.
3.QT interval prolongation caused by concomitant use of moxifloxacin hydrochloride injection and amiodarone hydrochloride for injection
Anqin ZHOU ; Min LUO ; Dengliang ZHANG ; Ting XU
Adverse Drug Reactions Journal 2020;22(1):42-43
A 75-year-old male received an IV infusion of moxifloxacin hydrochloride injection (moxifloxacin) 400 mg/d once daily for valvular heart disease complicated with heart failure and pulmonary infection. On the second day, the electrocardiogram showed that the corrected QT interval (QTc) was prolonged from 455 ms before treatment to 490 ms. On the third day, amiodarone hydrochloride for injection (amiodarone) 150 mg was given by slow intravenous injection in the early morning due to atrial fibrillation and 300 mg of amiodarone was continuously pumped at the speed of 30 mg/h at noon. In the afternoon of the 4th day, amiodarone 300 mg was given again via a pump at a speed of 30 mg/h. About 20 minutes later,the QTc was prolonged to 607 ms. On the 5th day, amiodarone was not given again, but the QTc continued to be prolonged up to 674 ms. On the 6th day, the QTc gradually returned to be within the normal range after discontinuation of moxifloxacin. The prolongation of QT interval in the patient was considered to be associated with moxifloxacin and amiodarone.
4.Effects of Assertive Community and Family Treatment on Family Environment and Compliance of Patients with Schizophrenia
Hongtao XIE ; Meifang TAO ; Yingjie JIA ; Dengliang CHEN ; Li SUN ; Chunyan ZHANG ; Zhen SHEN ; Zheng LU
Chinese Journal of Rehabilitation Theory and Practice 2017;23(1):114-117
Objective To explore the effects of assertive community and family treatment on family environment and compliance of patients with schizophrenia. Methods A total of 122 patients with schizophrenia discharged from January, 2014 to September, 2015 along with their families were enrolled and divided into intervention group (n=61) and control group (n=61). The intervention group received comprehensive intervention including family treatment by a professional team in the assertive community treatment model, while the control group received routine follow-up, for twelve months. They were evaluated with Positive and Negative Symptoms Scale (PANSS), Insight and Treatment Attitude Questionnaire (ITAQ), Family Environment Scale-Chinese Version (FES-CV), duration of pharmaceutical treatment and relapse rate before, and six and twelve months after intervention. Results There were statistically significant differences between the intervention group and the control group in total score of PANSS, score of ITAQ and FES-CV six and twelve months after intervention (FGroup>1.760, P<0.05); 16 patients in the control group and seven patients in the intervention group relapsed during the observation period (χ2=4.340, P=0.037). Kaplan-Meier survival analysis showed statistically significant difference between the two groups in duration of pharmaceutical treatment (χ2=6.338, P=0.012). Conclusion Assertive community and family treatment can improve intimacy between patients with schizophrenia and their family members, reduce high emotional expression, improve medication compliance, and reduce relapse.

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