1.Effect of MOTS-c on hepatocyte injury induced by glycochenodeoxycholic acid by regulating transporter MRP2 expression
Yu AO ; Xuyang ZHANG ; Dan TANG ; Gongwei LIU ; Dan HUANG ; Zhifang CAI
Organ Transplantation 2025;16(3):425-434
Objective To investigate the effects and related mechanisms of mitochondrial-derived peptide MOTS-c on glycochenodeoxycholic acid (GCDCA)-induced injury in human hepatocytes (THLE-3 cells). Methods THLE-3 cells were cultured in vitro and treated with different concentrations of GCDCA and MOTS-c. The optimal concentrations of GCDCA and MOTS-c were determined by cell counting kit (CCK)-8 method. Subsequently, THLE-3 cells were treated or pre-treated with GCDCA (200 µmol/L), MOTS-c (15, 30, 60 µmol/L), the multidrug resistance protein 2 (MRP2) inhibitor Probenecid (500 µmol/L), and the nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor ML385 (10 µmol/L). Cell proliferation was assessed by CCK-8 method. Lactate dehydrogenase (LDH) levels in the culture medium were measured by biochemical method. Cell apoptosis rates were determined by flow cytometry. MRP2 messenger RNA (mRNA) levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). MRP2 and Nrf2 protein expression levels were analyzed by Western blotting. Results As the concentration of GCDCA increased, the proliferation activity of THLE-3 cells gradually decreased, while LDH activity in the culture medium and apoptosis levels increased, and the expression levels of MRP2 in the cells decreased (all P<0.05). Treatment with 30 and 60 µmol/L MOTS-c significantly enhanced the proliferation activity of THLE-3 cells exposed to GCDCA, upregulated the expression of MRP2 and Nrf2, and reduced LDH activity and apoptosis levels (all P<0.05). Co-treatment with Probenecid partially reversed the protective effects of MOTS-c on GCDCA-induced THLE-3 cells injury, while co-treatment with ML385 partially inhibited the induction of MRP2 expression by MOTS-c in THLE-3 cells exposed to GCDCA. Conclusions MOTS-c may alleviate GCDCA-induced injury in human hepatocytes (THLE-3 cells), and its mechanism may be related to the upregulation of MRP2 expression mediated by Nrf2.
2.Changes of interleukin-34 levels in serum and bronchoalveolar lavage fluid of patients with severe pneumonia and their prognostic value
Yuxin LIU ; Yongmin YAN ; Jianke REN ; Jianlei TANG ; Sheliang XUE ; Zhifang ZHUANG ; Run CAI ; Yanjuan ZHOU
Journal of Clinical Medicine in Practice 2024;28(24):31-36
Objective To investigate the changes in interleukin-34 (IL-34)levels in serum and bronchoalveolar lavage fluid (BALF) of patients with severe pneumonia and their prognostic value. Methods A total of 66 patients with severe pneumonia (severe pneumonia group), 35 patients with non-severe pneumonia (non-severe pneumonia group), and 27 healthy adults (control group) were enrolled. The severe pneumonia group was further divided into survival group of 38 patients and non-survival group of 28 patients based on 28-day survival. Clinical data of all subjects were analyzed. Receiver operating characteristic (ROC) curves were plotted to assess the predictive power of serum IL-34 and relative
3.Clinical difference analysis and solution of lipid target and goal cut-off point determination of blood lipid management from different detection systems
Ruohong CHEN ; Fengxi WU ; Jingyao CAI ; Yiru ZHANG ; Zhifang ZHOU ; Min HU
Chinese Journal of Laboratory Medicine 2023;46(7):689-696
Objective:The results of the three lipid detection systems were compared to analyze their influence on risk stratification and clinical treatment in lipid management, especially the target goal cut-off point determination, and to find ways to reduce the impact on target goal determination of various lipid measurement system.Methods:A total of 196 serum samples with triglyceride TG <4.5 mmol/L were collected from people undergoing physical examinations and in-patients in the Second Xiangya Hospital of Central South University from August to October 2022. Triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were directly detected with Hitachi-Woke (HW), Roche and Mindray detection systems, respectively. The non high-density lipoprotein cholesterol (non HDL-C) was calculated by formula (TC-HDL-C) and LDL-C (F-LDL-C) was calculated by Friedewald formula, and results from various methodology were compared. The coefficient of variation ( CV) of these six indicators derived from the three detection systems were calculated to evaluate the consistency of the obtained results from different venders. In addition, the Pearson correlation coefficient was analyzed to evaluate the correlation of each indicator among different systems. According to the Chinese Guidelines for Blood Lipid Management, samples were divided into groups with LDL-C levels of <1.4, 1.4-<1.8, 1.8-<2.6, 2.6-<3.4 and ≥3.4 mmol/L according to the recommended LDL-C levels for different risk stratification levels. The sample size and percentage of LDL-C test results from different systems in the same group were counted to evaluate the impact of LDL-C differences between systems on clinical decision-making of blood lipid management. The correction factor was calculated through two methods: (1) The average deviation of LDL-C between systems was estimated by EP9-A3 method; (2) Multiple linear stepwise regression was used to establish the regression model of LDL-C difference and related indexes between systems. The two correction factors were used to correct the deviation of LDL-C value obtained from various systems, and Chi-square test was used to compare the difference of LDL-C grouping consistency rate before and after correction. Result:The average CV values of TG, TC, LDL-C, F-LDL-C, HDL-C, and non HDL-C among the three detection systems were 4.84%, 1.92%, 11.96%, 3.81%, 5.82% and 2.61%, respectively. Correlation analysis showed that when comparing the three systems in pairs, except for LDL-C derived from HW and Roche′s, and Mindray and Roche′s LDL-C ( R 2=0.938 and 0.947), the R 2 of other indicators were all greater than 0.97. The consistency rates of the three systems on LDL-C and F-LDL-C were 51.0% (100/196) and 90.8% (178/196), respectively, according to the risk stratification standard values and the difference was statistically significant ( P<0.05). When comparing in pairs, the consistency rates of Roche and HW, Mindray and HW, Mindray and Roche system LDL-C grouping were 60.7% (119/196), 82.7% (162/196), and 54.1% (106/196), respectively. After adjusting for mean deviation, the group consistency rate of Roche and HW increased to 73.7%-79.4% ( P<0.05), and the group consistency rate of Roche and Mindray increased to 72.3%-79.0% ( P<0.05). After adjusting for difference regression model, the group consistency rate of Roche and HW increased to 82.5%-84.0%, and the group consistency rate of Roche and Mindray increased to 81.0%-89.2%. However, there was no significant change in the group consistency rate of Mindray and HW after adjusting for both correction methods ( P>0.05) .Conclusions:There are significant differences in LDL-C derived from different detection systems, and the consistency rate of grouping according to the lipid-lowering standard value is relatively low, which may affect clinical decision-making in lipid management. Adjusted by the correction factor, the consistency rate of grouping between Roche and HW, Roche and Mindray systems with large differences in LDL-C can be improved. Using the difference multiple linear regression model as a correction factor is superior to the average deviation.
5.The effect of transcatheter arterial chemoembolization combined with ultrasound-guided radiofrequency ablation on the efficacy and immune function in patients with primary liver cancer
Wenhua WU ; Qinhui FENG ; Zhifang CAI ; Xiaoli JIA ; Ruihua YANG ; Shuangsuo DANG
Chinese Journal of Postgraduates of Medicine 2022;45(5):459-464
Objective:To investigate the effect of transcatheter arterial chemoembolization (TACE) combined with ultrasound-guided radiofrequency ablation (RFA) on the efficacy and immune function in patients with primary liver cancer.Methods:The clinical data of 152 patients with primary liver cancer from February 2019 to February 2021 in the Second Affiliated Hospital of Xi′an Jiaotong University were retrospectively analyzed. Among them, 76 patients were treated with TACE combined with RFA (combined group), and 76 patients were treated with TACE (control group). The efficacy was compared; the α-L fucosidase, T lymphocyte subsets (CD 3, CD 4, CD 8 and CD 4/CD 8), B lymphocyte subsets (CD 19) and tumor markers (alpha-fetoprotein, AFP; carcinoembryonic antigen, CEA; carbohydrate antigen 125, CA125) before treatment and 1 month after treatment were detected. Results:The total clinical effective rate in combined group was significantly higher than that in control group: 81.58% (62/76) vs. 52.63% (40/76), and there was statistical difference ( χ2 = 4.54, P<0.05). There were no statistical difference in all indexes before treatment between 2 groups ( P>0.05); the α-L fucosidase, AFP and CD 8 1 month after treatment in combined group were significantly lower than those in control group: (18.06 ± 5.33) U/L vs. (26.58 ± 7.75) U/L, (87.93 ± 22.55) μg/L vs. (146.83 ± 21.85) μg/L and 0.295 ± 0.052 vs. 0.367 ± 0.064, the CD 3, CD 4 and CD 4/CD 8 were significantly higher than those in control group (0.489 ± 0.054 vs. 0.462 ± 0.063, 0.363 ± 0.059 vs. 0.303 ± 0.075 and 1.43 ± 0.27 vs. 0.89 ± 0.14), and there were statistical differences ( P<0.01 or<0.05); there was no statistical difference in CEA, CA125 and CD 19 1 month after treatment between 2 groups ( P>0.05). Conclusions:TACE combined with RFA in the treatment of primary liver cancer patients can not only improve the total clinical effective rate, but also significantly improve the immune function, and help to reduce level of the liver tumor marker of AFP.
6.A preliminary model of case management for pregnancy-associated breast cancer
Pei AN ; Yan DING ; Hui WANG ; Zhifang CAI ; Li LI ; Maoli WANG
Chinese Journal of Nursing 2018;53(4):433-437
To explore the model of case management for patients with pregnancy-associated breast cancer in accordance with China's national conditions,and to improve the patients' compliance and satisfaction with the treatment.Case managers for patients with pregnancy-associated breast cancer were trained,and posts of case managers were established.Case managers,with the aid of multidisciplinary treatment teams and multi-specialized nursing groups,provided comprehensive,sustainable and coordinated care for patients with pregnancy-associated brcast cancer from diagnosis to 6 months after surgery.The model of case management for pregnancy-associated breast cancer could promote the treatment effectively,serving as important guarantee for multidisciplinary cooperation and providing patients with comprehensive,sustainable and coordinated care through mobilization of available resources.
7.Field research on clinical practice behavior of subspeciality nurses in department of gynaecology and obstetrics
Zheng ZHANG ; Chunyi GU ; Li LI ; Xiuhong WANG ; Xinli ZHU ; Zhifang CAI
Chinese Journal of Modern Nursing 2017;23(15):1971-1975
Objective To understand the clinical practice behavior and definite the role function of subspeciality nurses in department of gynaecology and obstetrics.Methods A total of 17 nurse specialisms in department of gynaecology and obstetrics were selected by purposive sampling with the method of field research. Participant observation was used in their clinical nursing activities. And then, field note were recorded timely. Besides, the data was sorted out and analyzed again and again.Results A total of six clinical practice behavior of subspeciality nurses in department of gynaecology and obstetrics were refined including specialty evaluation, professional skills, health education, psychological instruction, continuity management, and teaching and research.Conclusions The rudiment of mode of clinical practice of subspeciality nurses in department of gynaecology and obstetrics firstly appears at the present stage. It still needs to refer the mode of management and cultivation of nurse specialism abroad, improve the the clinical practice behavior and specialist team building of subspeciality nurses in department of gynaecology and obstetrics.
8.Correlation of HPV types with Th17 and Treg cells in cervical cancer
Donghui CAI ; Yan LI ; Runmei GUO ; Tingting ZHANG ; Zhifang CHEN
Chinese Journal of Clinical Oncology 2016;43(24):1099-1102
Objective:Based on the detection of CD4+IL17+Th17 and CD4+CD25+Foxp3+Treg cells in the peripheral blood of patients with human papilloma virus (HPV), the study analyzes the ratio of Th17 to Treg and compares the different expression of cytokine IL-17, IL-10, TGF-β, and IL-23 in the serum. Methods:From September 2014 to June 2016, 119 cases of untreated patients with cervical HPV in-fection were collected at the First Affiliated Hospital of Xinjiang Medical University, which include 46 cases of cervical cancer (CC), 43 cases with cervical intraepithelial neoplasia (CIN)Ⅱ-Ⅲ, and 30 with chronic cervicitis (CCS). The detection of HPV types classified 80 patients as high-risk and 39 as low-risk. Flow cytometry examined Treg and Th17 cells, and enzyme-linked immune sorbent assay was used to test related cytokines. Results:In the infection of high-risk cervical HPV, the rate of the CC group was 87%(40/46), which was higher than that of the CINⅡ-Ⅲgroup and the CCS group, which were 77%(33/43) and 23%(7/30), respectively. For the expression of Th17 and Treg cells in the peripheral blood and the related cytokine IL-17, IL-23, TGF-β, and IL-10 in the serum, the levels of CC group were also significantly higher than that of the other two groups, and the ratio of Th17 to Treg increased considerably with the se-verity of cervical lesions. The expression of Th17 and Treg cells in the peripheral blood of patients with high-risk cervical HPV were higher than that of patients with low-risk cervical HPV (P<0.05), which was the same for the expression of the related cytokine IL-17, IL-23, TGF-β, and IL-10 in the serum. The ratio of the Th17 to Treg of patients with high-risk cervical HPV increased remarkably (P<0.05). Conclusion:The expression of Treg and Th17 cells in high-risk patients exhibits an increasing trend, and the ratio of increased Th17 to Treg may directly participate in the process of HPV infection and immune evasion, which plays an important role in the occurrence and development of cervical cancer.
9.Antiviral treatment and long-term clinical outcome of decompensated cirrhotic patients with hepatitis C virus infection.
Fanpu JI ; Shuangsuo DANG ; Zhifang CAI ; Hongan XUE ; Na HUANG ; Layang LIU ; Shu ZHANG ; Yonghong GUO ; Xiaoli JIA ; Yuan WANG ; Zongfang LI ; Hong DENG
Chinese Journal of Hepatology 2015;23(9):647-652
OBJECTIVETo investigate the efficacy and safety of antiviral treatment in patients with hepatitis C virus (HCV) infection and decompensated cirrhosis and determine the effects of virological response on long-term prognosis.
METHODSSixty-six consecutive,interferon (IFN)-na(i)ve patients with HCV infection and decompensated cirrhosis were enrolled in this prospective study. All patients were given a 48-to 72-week course of IFN plus ribavirin (RBV) combined therapy,with a low accelerating dosage regimen using either:pegylated (PEG)-IFNa-2b at 1.0-1.5 mug/kg/week,PEG-IFNa-2a at 90-180 mug,or standard IFN-a-2b at 3MU,every other day.RBV was given at 800 to 1000 mg/day. All patients were routinely monitored for adverse drug reactions and virological response.Effects of treatments on patient survival were assessed by Kaplan-Meier analysis.
RESULTSAt the end of treatment,74.2% of patients were HCV RNA-negative,with 45.5% having achieved sustained virological response and 28.8% having relapsed;the remaining 25.7% of patients showed non-virological response (NVR). Among the patients with HCV genotype 1, 65.9% achieved end-of-treatment virological response (ETVR) and 34.1% achieved SVR;among the patients with HCV genotype 2,90.9% achieved ETVR and 68.2% achieved SVR. The positive and negative predictive values of early virological response (EVR) for ETVR were 95.7% and 75.0% respectively, and for SVR were 65.2% and 100% respectively. Compared with baseline,patients who achieved ETVR had better liver function,as evidenced by changes in levels of total bilirubin,alanine aminotransferase and albumin,as well as prothrombin activity and Child-Pugh score (t =4.564,11.486,2.303,2.699,3.694 respectively, all P less than 0.05).Compared with the NVR patients, the ETVR patients had lower risk of hepatic decompensation and hepatocellular carcinoma, and had improved survival (x2=18.756,6.992,7.580, respectively, all P less than 0.05).Twelve (18.2%) patients experienced serious adverse events,with 10 requiring premature treatment withdrawal and 2 dying.
CONCLUSIONAntiviral treatment for patients with HCV infection and decompensated cirrhosis using interferon in a low accelerating dosage regimen in combination with ribavirin is feasible.Patients who achieved ETVR had significantly improved long-term prognosis.
Alanine Transaminase ; Antiviral Agents ; therapeutic use ; Carcinoma, Hepatocellular ; Drug Therapy, Combination ; Genotype ; Hepacivirus ; genetics ; Hepatitis C ; diagnosis ; drug therapy ; Humans ; Interferon-alpha ; therapeutic use ; Kaplan-Meier Estimate ; Liver Cirrhosis ; drug therapy ; virology ; Liver Neoplasms ; Polyethylene Glycols ; therapeutic use ; Prospective Studies ; Recombinant Proteins ; therapeutic use ; Ribavirin ; therapeutic use ; Treatment Outcome
10.Effect of splenectomy on cellular immune function of patients with hepatitis C virus related cirrhotic portal hypertensionJ
Fanpu I ; Na HUANG ; Shu ZHANG ; Zhifang CAI ; An JIANG ; Rui ZHOU ; Baohua LI ; Song REN ; Zongfang LI
Chinese Journal of Hepatic Surgery(Electronic Edition) 2015;(4):232-236
ObjectiveTo investigate the effect of splenectomy on cellular immune function of patients with hepatitis C virus (HCV) related cirrhotic portal hypertension.MethodsTwelve patients with HCV-related cirrhotic portal hypertension undergoing splenectomy + pericardial devascularization in the Second Affiliated Hospital of Xi'an Jiaotong University between December 2011 and December 2013 were enrolled in this prospective study. Among the 12 patients, 4 were males and 8 were females withthe average age of (55±8) years old. Moreover, 12 healthy people were enrolled in the control group. The informed consents of all patients were obtained and the local ethical committee approval had been received. Percentage of natural killer (NK) cell, natural killer T (NKT) cell, CD4+ cell, CD8+T cell and CD4+/CD8+ ratio in peripheral blood before and 2, 6 weeks after splenectomy were observed. The comparison on different lymphocyte subsets was conducted using Wilcoxon rank-sum test.ResultsThe percentage of CD3-CD56+CD16+ NK cell 6 weeks after splenectomy was 7.7%, which was signiifcantly higher than 6.2% before splenectomy (T=1.992,P<0.05). And the percentage of CD56dim NK cell 2 and 6 weeks after splenectomy was respectively 94.9% and 96.4%, which was signiifcantly higher than 87.9%before splenectomy (T=2.747, 2.201;P<0.05). The percentage of CD56bright NK cell 2 and 6 weeks after splenectomy was respectively 3.8% and 2.4%, which was signiifcantly lower than 9.2% before splenectomy (T=2.747, 2.201;P<0.05). The percentage of CD3+CD56+ NKT cell 2 and 6 weeks after splenectomy was respectively 7.3% and 7.0%, which was significantly higher than 6.5% before splenectomy (T=2.275, 1.572;P<0.05). Percentage of CD4+ T cell 2 weeks after splenectomy was 41.7%, which was signiifcantly lower than 45.7% before splenectomy (T=3.059,P<0.05), and further decreased to 26.7% 6 weeks after splenectomy (T=2.201,P<0.05), while percentage of CD8+ T cell increased from 21.1% before splenectomy to 24.8% 2 weeks after splenectomy (T=2.432,P<0.05), and further increased to 35.3% 6 weeks after splenectomy (T=1.992,P<0.05). The CD4+/CD8+ ratio before splenectomy was 2.0 and decreased to 1.4 and 0.8 respectively 2 and 6 weeks after splenectomy (T=2.981, 1.992;P<0.05).ConclusionThe cellular immune function of patients with HCV related cirrhotic portal hypertension after splenectomy improves signiifcantly.


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