1.Expression of TFDP2 in placentas of women with preeclampsia and its effect on apoptosis of trophoblast cells
Chenrui CAO ; Dan LIU ; Zhiyin WANG ; Guangfeng ZHAO ; Zhongrui PEI ; Yali HU
Chinese Journal of Perinatal Medicine 2024;27(2):133-142
Objective:To investigate the expression level of transcription factor dimerization partner 2 (TFDP2) in the placentas of women with preeclampsia, and analyze its effect on the apoptosis of trophoblast cells.Methods:Placental tissues from thirty puerperae with preeclampsia who gave birth by cesarean section in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School between January 2018 and December 2022 (preeclampsia group) and 30 healthy puerperae undergoing cesarean section during the same period (control group) were retrospectively selected. Immunohistochemistry was used to localize TFDP2 in the placental tissues. Real-time quantitative-polymerase chain reaction (qRT-PCR) and Western blot were used to detect the differences in expression of TFDP2 at mRNA and protein levels in placental tissues between the two groups. Forskolin-exposed BeWo cells were transfected with small interfering RNA (siRNA) to knockdown TFDP2 and the changes in the expression of apoptosis-related indicators, B cell lymphoma 2 (Bcl2) and Bcl2 associated X (Bax), at protein and mRNA levels were analyzed by Western blot and qRT-PCR, respectively. Besides, the change in the apoptosis level of BeWo cells was detected using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining and flow cytometry. Downstream signaling pathways were analyzed to understand the involved molecular mechanisms. Two independent samples t-test, Wilcoxon rank-sum test, and Chi-square test were used for statistical analysis. Results:TFDP2 was mostly localized in the syncytiotrophoblasts and the extravillous trophoblasts in the normal placentas. TFDP2 expression in the syncytiotrophoblasts was lower in the preeclampsia group than in the control group at both mRNA (0.722±0.239 vs. 1.000±0.348, t=3.61, P=0.001) and protein (0.728±0.185 vs. 1.000±0.206, t=2.41, P=0.037) levels. Comparing the group without knockdown of TFDP2, the knockdown of TFDP2 in BeWo cells elevated the Bax/Bcl2 ratio (mRNA: 1.755±0.452 vs. 1.000±0.279, t=3.48, P=0.006; protein: 3.206±0.922 vs. 1.000±0.290, t=3.95, P=0.017), and increased cell apoptosis both in number and ratio (TUNEL staining: 4.556±1.740 vs. 2.444±1.130, t=3.05, P=0.008; flow cytometry: 21.37%±1.66% vs. 12.61%±0.38%, t=8.92, P=0.001). Furthermore, following TFDP2 knockdown, a decrease in the phosphorylation activity of catalytic subunit of protein kinase A (PKAc) at the Thr197 site was observed in the cytoplasm of BeWo cells (0.466±0.035 vs. 1.000±0.075, t=11.19, P<0.001) and a reduction in the expression of β-catenin in the cell nucleus was also detected (0.250±0.093 vs. 1.000±0.269, t=4.57, P=0.010). Conclusion:The expression of TFDP2 decreased significantly in the placentas of patients with preeclampsia, which may promote the apoptosis of syncytiotrophoblasts by inhibiting the PKAc/β-catenin signaling pathway.
2.Dynamic change and significance of Mindin protein in chronic hepatitis B treated with PEG-IFNα-2b
Yikai WANG ; Fengping WU ; Chenrui LIU ; Miao HAO ; Shasha LYU ; Miaomiao ZHANG ; Shuangsuo DANG ; Xin ZHANG
Journal of Clinical Hepatology 2024;40(1):52-57
ObjectiveTo investigate the change and potential role of Mindin protein in the treatment of chronic hepatitis B (CHB) with PEG-IFNα-2b. MethodsA total of 29 CHB patients who received the treatment with PEG-IFNα-2b in The Second Affiliated Hospital of Xi’an Jiaotong University from January 2018 to December 2019 were enrolled, and according to their clinical outcome, they were divided into cured group with 17 patients and uncured group with 12 patients. Peripheral blood samples were collected from both groups at baseline, 12 weeks, and 24 weeks to measure blood routine indices, liver function parameters, hepatitis B markers, and Mindin protein. HBsAg, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and Mindin protein at different time points were compared between the two groups. The independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; a Spearman correlation analysis was used to investigate correlation; a multiple linear regression analysis was used to investigate the influence of HBsAg and ALT on the content of Mindin protein. ResultsThe analysis of baseline data showed that there were significant differences in the levels of HBsAg, HBeAb, albumin, and albumin/globulin ratio between the cured group and the uncured group (all P<0.05). The cured group tended to have a gradual increase in the level of Mindin, and the level of Mindin at 24 weeks was significantly higher than that at baseline (P<0.05). The cured group had a significantly higher level of Mindin protein than the uncured group at 24 weeks (P=0.019). The cured group had a significantly lower level of HBsAg than the uncured group (P<0.05), with a significant change from baseline to each time point within the cured group (P<0.05). In addition, the levels of ALT and AST in the cured group tended to first increase and then decrease, and the expression levels at 12 weeks were significantly higher than those at baseline (P<0.05). At 12 weeks, there was a strong linear correlation between Mindin protein levels and ALT in the untreated group (r=0.760 8, P<0.05), and further multiple linear regression analysis also demonstrated a linear relationship between the two (b=1.571, P=0.019). ConclusionThere is a significant difference in the level of Mindin protein between the cured group and the non-cured group after 24 weeks of PEG-IFNα-2b antiviral treatment, and therefore, detecting the dynamic changes of Mindin protein can better predict the treatment outcome of CHB, which provides a reference for clinical practice.
3.Research progress on the physiological mechanism and regulatory network of orchitis treatment
Yujie YANG ; Zhuoxin LI ; Chenrui WANG ; Jiahe LIU ; Qiushuang YU ; Qi HOU
Journal of Modern Urology 2024;29(11):969-974
Orchitis is a common male genitourinary disorder that significantly impacts patients' life quality.Current treatment strategies have certain limitations and side effects.Ongoing therapeutic strategies focus on the interactions and regulatory networks among pathways and factors involved in the progression of orchitis.The targeted pharmacological agents include inflammatory pathways (p38MAPK, NF-κB, PI3K/Akt), cytokines (TNF-α, IL-6), and the nitric oxide synthase (NOS) system.However, these studies are currently at the animal research stage, and further clinical investigations are necessary to validate their efficacy and safety before clinical use.This article reviews the preclinical animal studies on new treatment methods of orchitis from the aspects of autoimmunity and exogenous microorganism induction, including ketotifen furmarate, aspirin, L-NAME, activin A, cortisol, melatonin, methane, long non-coding RNA MEG3, Abaloparatide, recombinant type Ⅰ interferon, and so on.
4.Expression and clinical significance of laboratory of genetics and physiology 2, retinoic acid inducible gene I and melanoma differentiation associated gene 5 in children with hand, foot and mouth disease
Meng ZHANG ; Muqi WANG ; Miao HAO ; Xinyu WANG ; Chenrui LIU ; Yuan CHEN ; Yufeng ZHANG ; Shuangsuo DANG ; Huiling DENG ; Yaping LI
Chinese Pediatric Emergency Medicine 2023;30(10):750-755
Objective:To detect the expression levels of laboratory of genetics and physiology 2 (LGP2), retinoic acid inducible gene I (RIG-I) and melanoma differentiation associated gene 5 (MDA5) in children with hand, foot and mouth disease (HFMD), and to explore their possible clinical significance in HFMD.Methods:Fifty children with HFMD, who visited Second Affiliated Hospital of Xi′an Jiao Tong University, Xi ′an Children′s Hospital and Xi ′an Central Hospital from May 2020 to May 2021, were selected as the research subjects, and 20 children with physical examination at the same age during the same period were selected as the control group.Children with HFMD were divided into enterovirus 71 (EV-A71) type and coxsackievirus A6 (CV-A6) type according to the results of pathogen detection, and then divided into mild group and severe group according to the severity of the disease.The relative mRNA expression levels of LGP2, RIG-I and MDA5 in each group, and the correlation among the three proteins were compared and analyzed.Results:Among 50 cases of HFMD, 26 cases were EV-A71 type (16 cases were mild and 10 cases were severe) and 24 cases were CV-A6 type (17 cases were mild and 7 cases were severe). There was no significant difference in age and sex between HFMD group and control group ( P>0.05). The relative expression levels of LGP2 mRNA in EV-A71 and CV-A6 HFMD cases were 2.37(1.78, 3.25)% and 1.88 (1.35, 3.13)%, lower than that in control group [2.97(2.61, 3.55)%]. Only the difference between CV-A6 HFMD children and control group was statistically significant ( Z=-2.310, P=0.021). The relative expression levels of RIG-I mRNA in EV-A71 and CV-A6 HFMD cases were 9.95 (7.79, 14.62)% and 9.78(7.04, 15.83)%, lower than that in control group [18.47(13.00, 21.07)%]. The differences were all statistically significant ( P<0.05). The relative expression levels of MDA5 mRNA in EV-A71 and CV-A6 HFMD cases were 4.41(2.82, 5.99)% and 3.98 (2.18, 7.41)%, lower than that in control group [5.10(3.52, 7.71)%], but the differences were not statistically significant.There were no significant differences in the relative expression levels of the three indicators between the mild and severe groups of children with EV-A71 or CV-A6 HFMD.The expression levels of LGP2, RIG-I and MDA5 mRNA were highly correlated( P<0.001). Conclusion:The relative expression levels of LGP2, RIG-I and MDA5 mRNA in children with HFMD are decreased in different degrees than those in normal children.And there is a correlation among them.
5.Risk factors for osteopenia/osteoporosis and the diagnostic value of CT value in patients with chronic hepatitis B
Jingyi ZHANG ; Yingmei TANG ; Jiaqi LI ; Qian WANG ; Chenrui ZHANG
Journal of Clinical Hepatology 2022;38(5):1041-1047
Objective To investigate the value of the CT values of thoracolumbar vertebrae measured by abdominal CT in the diagnosis of osteopenia/osteoporosis in patients with chronic hepatitis B, as well as the risk factors for osteopenia/osteoporosis in such patients. Methods A retrospective analysis was performed for 112 patients with chronic hepatitis B in the Second Affiliated Hospital of Kunming Medical University from January 2019 to December 2020. All patients underwent abdominal CT, and some patients underwent dual-energy X-ray absorptiometry (DXA). The CT values of T12 vertebral body to L3 vertebral body were measured, and the value of CT value of each vertebral body in the diagnosis of osteopenia/osteoporosis was analyzed in comparison with T-score of L1-L4 vertebral bodies measured by DXA. With the CT values of vertebral bodies as the diagnostic criteria, the patients with chronic hepatitis B enrolled were divided into osteopenia/osteoporosis group with 55 patients and normal bone mass group with 57 patients. Clinical features and biochemical parameters were compared between the two groups to analyze the risk factors for osteopenia/osteoporosis in patients with chronic hepatitis B. The t -test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test, the Fisher's exact test, and the Bonferroni correction test were used for comparison of categorical data between groups. A Pearson correlation analysis was performed to investigate correlation, and a binary logistic regression analysis was used for multivariate analysis. The receiver operating characteristic (ROC) curve was used to investigate the value of CT values of T12-L3 vertebral bodies in the diagnosis of osteopenia/osteoporosis in patients with chronic hepatitis B. The Kappa test was used check consistency. Results A total of 46 patients who completed abdominal CT and DXA during the same time of hospitalization were analyzed, and their CT values of T12-L3 vertebral bodies were significantly positively correlated with the T-score values of L1-L4 vertebral bodies in DXA ( r T12 =0.694, r L1 =0.661, r L2 =0.781, r L3 =0.685, all P < 0.001). The ROC curve analysis showed that the CT value of L2 vertebral body had the largest area under the ROC curve of 0.863 and showed a good accuracy in the diagnosis of osteopenia/osteoporosis, which was consistent with the results of DXA ( K =0.648, P < 0.001). The clinical features and biochemical parameters of 112 patients with chronic hepatitis B were analyzed, and it was suggested that old age (odds ratio [ OR ]=1.108, 95% confidence interval [ CI ]: 1.026-1.196, P =0.009) and sarcopenia ( OR =2.788, 95% CI : 1.009-7.707, P =0.048) were the risk factors for osteopenia/osteoporosis. Conclusion The patients with chronic hepatitis B often need regular abdominal CT to evaluate the progression of liver disease, and it is of high clinical significance to identify the presence or absence of osteopenia/osteoporosis and sarcopenia by measuring the CT value of L2 vertebral body and skeletal muscle area of L3 vertebrae plane, thereby giving timely intervention and improving patients' prognosis and quality of life.
6.Research advances in glucose and lipid metabolism disorders in different types of chronic liver diseases
Qian WANG ; Chenrui ZHANG ; Yingmei TANG
Journal of Clinical Hepatology 2022;38(8):1937-1940
The liver is an important metabolic organ in the body. Studies have shown that chronic liver disease is closely associated with glucose and lipid metabolism disorders, and different types of liver diseases often show different characteristics of glucose and lipid metabolism. This article reviews the epidemiological characteristics, disease severity, pathogenesis, and treatment methods of glucose and lipid metabolism disorders in different types of chronic liver diseases, so as to improve the awareness among clinicians.
7.Dynamic changes of serum hepatitis B virus DNA and HBsAg in patients with chronic hepatitis B treated with tenofovir disoproxil fumarate for 3 years
Rui LU ; Shuangsuo DANG ; Yixin LIU ; Yikai WANG ; Chenrui LIU ; Yaping LI ; Fengping WU ; Mei LI
Journal of Clinical Hepatology 2022;38(10):2224-2229
Objective To assess the efficacy of tenofovir disoproxil fumarate (TDF) in chronic hepatitis B (CHB) patients receiving antiviral therapy for three years. Methods A total of 157 CHB patients treated with TDF alone for ≥3 years from January 2015 to August 2020 in the Second Affiliated Hospital of Xi'an Jiaotong University were retrospectively studied. The patients were divided into HBeAg-positive and HBeAg-negative groups based on their baseline HBeAg levels. The data of serum HBV DNA and HBsAg levels at baseline, the first, second and third year of treatment were collected to analyze the dynamic changes. The t -test was used to compare continuous variables with normal distributions between two groups, while the Mann-Whitney U test was used to compare continuous variables with non-normal distribution between two groups. Repeated measurement data with non-normal distribution were first transformed into logarithms and the intra- or between-group comparison was performed using repeated measures analysis of variance. The chi-square test or Fisher exact test was used to compare categorical variables between groups. Results HBV DNA clearance rate in HBeAg-positive patients was significantly lower than that in HBeAg-negative patients during the first and second years of TDF treatment (1st year: 65.8% vs 81.0%, χ 2 =4.676, P < 0.05; 2nd year: 87.7% vs 98.8%, Fisher exact test, P < 0.05). When TDF treatment was given for three years, there was no significant difference in HBV DNA clearance rates (97.3% vs 100%, Fisher exact test, P > 0.05). The baseline HBsAg levels in HBeAg-positive and HBeAg-negative patients were 10 633.6 (2 084.8-24 005.7) IU/mL and 1 402.8 (311.0-2 863.5) IU/mL, respectively, and decreased to 1 534.9 (912.7-5 885.9) IU/mL and 677.8 (119.4-1 974.8) IU/mL after 3 years of TDF treatment, with a significant difference between two groups ( F =25.456, P < 0.001). In HBeAg-positive patients, the median decline value of HBsAg level was significantly higher in the first year [1 856.5 (158.4-12 103.1) IU/mL] than in the second year [879.8 (130.5-2 382.5) IU/mL] or the third year [479.9 (95.0-1 662.4) IU/mL] ( F =10.972, P < 0.001), while there was no significant difference in HBeAg-negative patients ( F =0.513, P > 0.05). In addition, after 3 years of TDF treatment, 59.2% of patients achieved HBsAg < 1500 IU/mL, with a HBsAg negative rate of 1.3%. Conclusion After 3 years of TDF treatment, all HBeAg-negative CHB patients can achieve HBV DNA negative conversion; for HBeAg-positive CHB patients, 97.3% of them achieved HBV DNA negative conversion, while 2.7% of them were still HBV DNA detectable. The HBsAg level declined over treatment time, and the decline rate of HBsAg level in HBeAg positive patients showed a trend of "first fast and then slow". After 3 years of TDF treatment, 59.2% of patients achieved HBsAg < 1500 IU/mL.
8.Quantitative detection of red blood cell antibody-mediated complement activation
Zhongying WANG ; Jian LI ; Fengyong ZHAO ; Chenrui QIAN ; Wei SHEN ; Liangfeng FAN ; Sha JIN ; Jiewei ZHENG ; Yuyu ZHANG ; Dong XIANG
Chinese Journal of Blood Transfusion 2022;35(9):982-985
【Objective】 To construct an in-vitro model of erythrocyte antibody-mediated complement activation, and establish quantitative detection methods based on flow cytometry and spectrophotometry, so as to explore the correlation of anti-body titers and complement activation speed, and provide a methodological basis for studying the adverse transfusion reactions of anti-body mediated complement hemolysis. 【Methods】 Mouse monoclonal antibody that recognized human C3b and fluorescent secondary antibody were used to label C3b fragments on erythrocytes, and the deposition of C3b fragments after complement activation was detected by flow cytometry. The absorbance at 540 nm of the supernatant in the complement activation reaction system was measured by spectrophotometry as the amount of hemoglobin released was related to the absorbance. 【Results】 The complement activation system was constructed according to the ratio of 3% red blood cell suspension (mixed for 6 people) 1∶anti-Tja 1∶complement 2. The repeatability was good (P value>0.05) as different red blood cell mixtures had been used to repeat the detection reaction system. When using 32×, 64× and 128× dilutions of anti-Tja mediated complement activation, the deposition of C3b fragments has been detected by flow cytometry at 30 s, 1 min and 2 min, respectively, and MFI peaked at 5 min, 10 min and 30 min, respectively. No obvious hemolysis has been observed within 1.5 h. 【Conclusion】 In vitro model of anti-Tja-mediated complement activation demonstrates the speed of complement activation is related to the concentration of antibody. At a certain antibody concentration, the speed of complement activation has been slowed down, and no obvious hemolysis observed.
9.Clinical efficacy of hepatic artery infusion chemotherapy combined with immunotherapy plus target therapy for advanced hepatocellular carcinoma
Hongxiang CAO ; Rui LIAO ; Qiang HE ; Long PAN ; Yi ZHAO ; Yongchen WANG ; Junjie HUANG ; Chenrui WU ; Ruirui SUN ; Ping HUANG
Chinese Journal of Digestive Surgery 2021;20(S2):41-44
Primary liver cancer is one of the common malignant tumors and its mortality ranks third in the world. Because there are no obvious symptoms in the early stage of liver cancer, most patients are diagnosed as advanced stage, without the opportunity of surgical resection. The authors report a case of hepatocellular carcinoma with portal vein tumor thrombus, which reduced significantly after hepatic artery infusion chemotherapy combined with bevacizumab and atezolizumab, showing the safety and efficacy.
10.Risk factors for lower extremity amputation in patients with diabetic foot
Bo XU ; Caizhe YANG ; Shibai WU ; Da ZHANG ; Luning WANG ; Li XIAO ; Ying CHEN ; Chenrui WANG ; Ao TONG ; Xiufang ZHOU ; Xiaohong LI ; Xiaohong GUAN
Chinese Journal of Internal Medicine 2017;56(1):24-28
Objective To explore the risk factors for lower extremity amputation in patients with diabetic foot.Methods The clinical data of 1 771 patients with diabetic foot at the Air Force General Hospital of PLA from November 2001 to April 2015 were retrospectively analyzed.The patients were divided into the non-amputation and amputation groups.Within the amputation group , subjects were further divided into the minor and major amputation subgroups.Binary logistic regression analyses were used to assess the association between risk factors and lower extremity amputation.Results Among 1 771 patients with diabetic foot , 323 of them ( 18.24%) were in the amputation group ( major amputation: 41; minor amputation:282 ) and 1 448 ( 81.76%) in the non-amputation group.Compared with non-amputation patients, those in the amputation group had a longer hospital stay and higher estimated glomerular filtration rate(eGFR)levels.Fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), C-reaction protein (CRP), ESR, ferritin, fibrinogen and WBC levels of the amputation group were higher , while hemoglobin albumin, transferrin, TC, TG, HDL-C and LDL-C were lower than those of the non-amputation group (all P<0.05 ).The proportion of hypertension ( 52.48% vs 59.98%) , peripheral vascular disease ( PAD ) (68.11% vs 25.04%), and coronary heart disease (21.33% vs 28.71%) were different between the amputation and non-amputation groups (all P<0.05).Multivariable logistic regression analyses showed that Wagner′s grade , PAD and CRP were the independent risk factors associated with lower extremity amputation in hospitalized patients with diabetic foot.Conclusion Wagner′s grade, ischemia of lower limbs and infection are closely associated with amputation of diabetic foot patients.

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