2.Risk factors for cardiovascular and cerebrovascular morbidity and mortality in maintenance hemodialysis patients
Huijuan MA ; Hua TANG ; Linsheng LYU ; Yanni WANG ; Caixia WANG ; Xun LIU ; Tanqi LOU
Chinese Journal of Nephrology 2015;31(9):652-657
Objective To identify the risk factors associated with cardiovascular and cerebrovascular disease (CCVD) in maintenance hemodialysis (MHD) patients. Methods We analyzed all of the patients undergoing maintenance hemodialysis in the dialysis center of the 3rd Affiliated Hospital of Sun Yat-sen University for at least 3 months from Jan 1st, 2009 to Dec 31st, 2014. Baseline and yearly interval clinical data were recorded and patients were followed up until morbidity or death of CCVD. Cox proportional hazard regression and time-dependent Cox regression were used to estimate the relative risk of outcomes associated with clinical measurements. Results There were 243 patients enrolled in the study, with a mean age of (53.2 ± 16.4) years old, and 138 of them were male (56.8%). The multivariate Cox proportional model revealed that age (HR=1.040, 95%CI:1.015-1.065, P=0.002), Erythropoietin (EPO) dose (HR=0.914, 95%CI: 0.846-0.987, P=0.022) and history of cardiovascular and cerebrovascular disease (HR=4.045, 95%CI: 2.074-7.890, P<0.001) were independent predictors of CCVD in MHD patients. After adjusting for baseline predictors, time-dependent serum phosphorus level (HR=1.722, 95%CI: 1.034-2.866, P=0.037) was significantly associated with CCVD. Conclusion Older age, decreases in EPO dose and history of cardiovascular and cerebrovascular disease were associated with increased risks of CCVD in MHD patients. Increase in serum phosphorus level was associated with increased risks of CCVD in a time-dependent manner.
3.Reactions of mitochondrial mitofusion 1 and fission 1 proteins and membrane potential of human neuroblastoma cells to fluoride exposure
Rongrong MA ; Dan ZHENG ; Kailin ZHANG ; Jigang PAN ; Yanjie LIU ; Zhizhong GUAN ; Didong LOU ; Yanni YU
Chinese Journal of Endemiology 2018;37(1):19-23
Objective To evaluate the influence of fluoride on mitochondrial membrane potential of neuroblastoma SH-SY5Y cells,and on the expression levels of mitochondrial proteins mitofusion 1 (Mfn1) and fission 1 (Fis1).Methods A stable and feasible culture method of SH-SY5Y cells in vitro was established with different concentration of sodium fluoride [0.0 (control),0.4,2.0 and 4.0 mmol/L],and various periods exposure of 6,12,24,48 h;the mitochondrial membrane potential of SH-SY5Y cells was detected by mitochondrial membrane potential assay kit (JC-1);and the expression levels of Mfn1 and Fis1 proteins were detected by Western blotting.Results Compared with the control group (1.63 ± 0.18,1.13 ± 0.15,1.30 ± 0.02) for various periods exposure (6,12,48 h),the red/green fluorescence ratios of the mitochondrial membrane potential of SH-SY5Y cells exposed to 2.0 and 4.0 mmol/L of sodium fluoride were decreased significantly (1.01 ± 0.10,0.80 ± 0.04;0.75 ± 0.13,0.62 ± 0.10;0.82 ± 0.01,0.56 ± 0.04,P < 0.05);compared with the control group (0.93 ± 0.03,1.05 ± 0.07,1.17 ± 0.04) for various periods exposure,the expression levels of mitochondrial Mfn1 protein were decreased significantly in 0.4,2.0,4.0 mmol/L sodium fluoride groups (6,12,48 h:0.75 ± 0.02,0.65 ± 0.05,0.57 ± 0.06;0.83 ± 0.06,0.79 ± 0.06,0.69 ±0.06;0.98 ± 0.05,0.73 ± 0.07,0.62 ± 0.09,P < 0.05).Compared with the control group (0.90 ± 0.05) for exposure time 12 h,the expression levels of Fis1 protein were increased significantly in 2.0,4.0 mmol/L sodium fluoride groups (1.14 ± 0.06,1.23 ± 0.06,P < 0.05).Conclusions The mitochondrial membrane potential and the expression levels of mitofusion 1 and fission 1 of SH-SY5Y cells treated with fluoride are abnormal,which might be associated with the theory of nerve cell damage from high oxidative stress.
4.Effects of silencing fisson 1 gene on mitofusion and mitochondrial membrane potential in SH-SY5Y cells induced by fluoride
Rongrong MA ; Dan ZHENG ; Xiaorong YANG ; Shimei HUANG ; Kailin ZHANG ; Yanni YU ; Zhizhong GUAN ; Didong LOU
Chinese Journal of Endemiology 2018;37(4):278-282
Objective To investigate the influence of inhibited gene expression of fisson 1 (Fis1) gene on the level of Fis1,mitofusin 1 (Mfn1) and mitochondrial membrane potential in SH-SY5Y cells with fluorine,to study the role of mitochondrial dynamic balance in the pathogenesis of chronic fluorosis.Methods SH-SY5Y cells were cultured in vitro,when adherent cells entered the logarithmic phase,using a group design,they were divided into four groups:blank control group (control),fluoride group [2 mmol/L sodium fluoride (NaF)],fluoride negative control group (2 mmol/L NaF + non-specific siRNA) and the gene-silencing group (2 mmol/L NaF + specific siRNA-Fis1).The protein expression levels of Fis1 and Mfn1 were measured by Western blotting;the mRNA expression levels of Fis1 and Mfn1 were measured by Real-time PCR;and the levels of the mitochondrial membrane potential was detected by mitochondrial membrane potential detection kit.Results Compared with control (1.37 ± 0.18,1.00 ± 0.04;1.57 ± 0.19,1.00 ± 0.04;1.00 ± 0.10),the expression levels of Fisl protein (1.72 ± 0.04) and mRNA (1.48 ± 0.13) in fluoride group were increased,the expression levels of Mfn1 protein (0.87 ± 0.02) and mRNA (0.69 ± 0.07) in fluoride group were decreased,the level of mitochondrial membrane potential (0.76 ± 0.13) was decreased (P < 0.05).Compared with control,the expression levels of Fis1 protein (0.79 ± 0.07) and mRNA (0.06 ± 0.03) in gene-silencing group were decreased,the expression levels of Mfn1 protein (1.71 ± 0.04) and mRNA (1.52 ± 0.05) in gene-silencing group were increased (P < 0.05),the level of mitochondrial membrane potential (0.94 ± 0.01) was decreased.Compared with fluoride group,the expression levels of Fis1 protein and mRNA in gene-silencing group were decreased,the expression levels of Mfn1 protein and mRNA in gene-silencing group were increased,the level of mitochondrial membrane potential in gene-silencing group was increased (P < 0.05).Conclusion Gene expression inhibition of Fis1 gene can reduce the mitochondrial division and damage of mitochondrial membrane potential in SH-SY5Y cells induced by fluoride.
5.Whole-lesion histogram analysis of apparent diffusion coefficient for the prediction of pathological complete response to neoadjuvant chemotherapy in different subtypes of breast cancer
Xiao WANG ; Liyu ZHU ; Xiaoming ZHA ; Hongli LIU ; Siqi WANG ; Jianjuan LOU ; Qigui ZOU ; Cong WANG ; Jue WANG ; Yanni JIANG
Chinese Journal of Radiology 2020;54(4):338-344
Objective:To investigate the value of whole-lesion histogram parameters of apparent diffusion coefficient (ADC) in evaluating and predicting the pathological complete response(PCR) to neoadjuvant chemotherapy (NAC) in different subtypes of breast cancer.Methods:This retrospective study included 117 patients with breast cancer who underwent MRI examination before NAC prior to surgery from January 2016 to December 2017 in the First Affiliated Hospital of Nanjing University. All cases were divided into Luminal B, HER2 positive ( n=21) and triple negative ( n=26) groups. The surgical pathology after chemotherapy was evaluated by Miller-Payne (M-P) system and the patients were divided into PCR group and non-PCR (nPCR) group. Firevoxel software was used to generate the whole-lesion ADC histogram. The parameters included mean (ADC mean), skewness, kurtosis, the minimum (ADC min), the maximum (ADC max), 10th percentile(ADC 10%), 50th percentile (ADC 50%) and 90th percentile (ADC 90%). The two independent samples t test or Mann-Whitney U test was used to compare the differences between PCR and nPCR groups in each subtype. The diagnostic performance of statistically different ADC parameters for predicting PCR was evaluated by receiver operating characteristic (ROC) curve. Results:Kurtosis was significantly higher in PCR group than that in nPCR group in HER2 positive subtype ( P=0.039). It achieved an area under the curve (AUC) of 0.813 with sensitivity of 100% and specificity of 68.7% at the optimal cutoff value (1.861) for differentiating PCR from nPCR cases. In triple negative subtype, ADC mean and ADC 50% were smaller in PCR group than those in nPCR group ( P=0.028,0.013). They achieved AUCs of 0.800, 0.842, respectively. When ADC mean of 1.030×10 -3 mm 2/s and ADC 50% of 0.976×10 -3 mm 2/s were used as cutoff value to differentiate PCR from nPCR, the sensitivities were 75.0%, 80.0% and the specificities were 83.3%, 83.3%, respectively. Conclusion:Kurtosis can predict post-NAC PCR in patients with HER2 positive breast cancer, while ADC 50% has a high value in predicting post NAC PCR of triple negative breast cancer patients.
6.Clinical characteristics of patients with malignant tumors and immune checkpoint inhibitors related multisystem adverse events as well as therapeutic efficacy of immune checkpoint inhibitors: a retrospective study
Xingyu LU ; Xu ZHANG ; Chongxiang XUE ; Meng YANG ; Zhiqiang CHENG ; Liya LI ; Yanni LOU ; Chao WANG ; Huijuan CUI
Cancer Research and Clinic 2023;35(5):328-333
Objective:To investigate the clinical characteristics of patients with malignant tumors and immune checkpoint inhibitors (ICI) related multisystem adverse events as well as therapeutic efficacy of ICI.Methods:The general data, immune-related adverse events (irAE) type, onset time, severity and ICI efficacy of patients with malignant tumors who developed irAE after receiving ICI in China-Japan Friendship Hospital between January 2019 and November 2021 were retrospectively analyzed. All patients were divided into multisystem irAE group and single system irAE group according to whether patients with more than 1 organ or system developed irAE for once. The occurrence of irAE was summarized, and the clinical characteristics of patients were compared. Progression-free survival analysis was not performed owing to the pause of immunotherapy caused by some irAE, so the efficacy of ICI was evaluated by using ICI treatment duration (TD).Results:A total of 47 patients with malignant tumors and irAE were included in this study, with 70 times of irAE in total. The median onset time was 90 d (35 d, 196 d). Among them, 12 patients (25.53%) developed multisystem irAE (32 times of irAE in total); the other 35 patients (74.47%) developed single system irAE (38 times of irAE in total). Cutaneous toxicity for 7 times, thyroid toxicity for 7 times and pulmonary toxicity for 5 times were the most frequent among multisystem irAE group; pulmonary toxicity for 13 times, thyroid toxicity for 12 times and cutaneous toxicity for 5 times were the most frequent among single system irAE group. There were no statistically significant differences in the proportion of patients stratified by age, gender, the combination of other treatments and different body mass between the two groups (all P > 0.05). The median follow-up time was 20 months (9-40 months). The median TD of ICI was 16.00 months (95% CI 3.62-31.22 months) in multisystem irAE group and 4.60 months (95% CI 4.12-11.30 months) in single system irAE group; TD in multisystem irAE group was longer than that in single system irAE group, and the difference was statistically significant ( HR = 0.413, 95% CI 0.202-0.844, P = 0.038). Conclusions:The efficacy of ICI in patients with malignant tumors and multisystem irAE is better than that in those with single system irAE. It suggests that the better efficacy of ICI may be associated with greater risk of irAE. There is no significant difference in the clinical features between multisystem irAE and single system irAE.
7.Expert Consensus on Clinical Diseases Responding Specifically to Traditional Chinese Medicine: Pulmonary Nodules
Mingwei YU ; Huairui ZHANG ; Xinghan ZHANG ; Xiao LI ; Rengui WANG ; Zhiqiang LONG ; Zhen WANG ; Bo PANG ; Jianwei HUO ; Wei CHEN ; Yong ZHU ; Baoli LIU ; Yanni LOU ; Ganlin ZHANG ; Jiayun NIAN ; Mei MO ; Xiaoxiao ZHANG ; Guowang YANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(6):238-245
In recent years, the incidence of pulmonary nodules has kept rising. To give full play to the advantages of traditional Chinese medicine (TCM) in the treatment of pulmonary nodules and identify the breakthrough points of integrating TCM with Western medicine, the China Association of Chinese Medicine organized medical experts in TCM and western medicine to carry out in-depth discussion regarding this disease. The discussion encompassed the modern medical advances, TCM theories of etiology and pathogenesis, the role and advantages of TCM in the whole course management of pulmonary nodules, contents and methods of research on pulmonary nodules, and science popularization work, aiming to provide a reference for clinical practice and scientific research. After discussion, the experts concluded that the occurrence of pulmonary nodules was rooted in the deficiency of the lung and spleen and triggered by phlegm dampness, blood stasis, and Qi stagnation. TCM can treat pulmonary nodules by controlling and reducing nodules, improving physical constitution, ameliorating multi-system nodular diseases, reducing anxiety and avoiding excessive diagnosis and treatment, and serving as an alternative for patients who are unwilling or unfit for surgical treatment. At present, the optimal diagnosis and treatment strategy for pulmonary nodules has not been formed, which needs to be further studied from multiple perspectives such as clinical epidemiology, biology, and evidence-based medicine. The primary task of current research is to find out the advantages, effective prescriptions, and target populations and determine the effective outcomes of TCM in the treatment of pulmonary nodules. At the same time, basic research should be carried out to explore the etiology and biological behaviors of pulmonary nodules. The expert consensus on the diagnosis and treatment of pulmonary nodules with integrated TCM and Western medicine needs to be continuously revised to guide clinicians to conduct standardized, scientific, and accurate effective diagnosis and treatment.