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Objective:To investigate the clinical efficacy and safety of demethylating drugs decitabine and azacitidine in treatment of myelodysplastic syndromes (MDS).Methods:The clinical data of 15 patients initially diagnosed with MDS in Fujian Provincial Hospital from May 2010 to May 2020 were retrospectively analyzed; 10 patients were treated with decitabine (10-30 mg·m -2·d -1, 3-5 d consecutively) and 5 patients were treated with azacitidine (75 mg·m -2·d -1 for 7 d consecutively). Gene mutation, risk stratification, efficacy and adverse reactions were observed. Results:Among 15 patients, 9 cases were males and 6 cases were females, with a median age of 64 years (51-84 years). The median follow-up time was 18 months (4-62 months). There were 3 cases in high-risk group, 10 cases in medium-risk group and 2 cases in low-risk group. SF3B1, TET2 and STAG2 mutations were more common in patients with low to moderate risk; DNMT3A, EZH2, U2AF1, RUNX1 and TP53 mutations were more common in patients with high-risk. All patients were evaluated for efficacy after 2-3 courses of treatment, and the total effective rate was 66.7% (10/15). Among them, 1 case (6.7%) achieved complete remission, 1 case (6.7%) achieved bone marrow complete remission (mCR), 2 cases (13.3%) achieved partial remission, and 6 cases (40%) achieved hematological improvement. During the treatment, 9 cases had grade 3-4 hematological toxicity and 6 cases had grade 3-4 infection. There was no grade 3-4 bleeding, nausea, vomiting and liver function damage. During the follow-up to May 2020, 9 patients survived and 6 patients died.Conclusions:Demethylating drugs decitabine and azacitidine have high rates of complete remission and partial remission and a low rate of adverse drug reactions in MDS patients.
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BACKGROUND@#The 2019 novel coronavirus has caused the outbreak of the acute respiratory disease in Wuhan, Hubei Province of China since December 2019. This study was performed to analyze the clinical characteristics of patients who succumbed to and who recovered from 2019 novel coronavirus disease (COVID-19).@*METHODS@#Clinical data were collected from two tertiary hospitals in Wuhan. A retrospective investigation was conducted to analyze the clinical characteristics of fatal cases of COVID-19 (death group) and we compare them with recovered patients (recovered group). Continuous variables were analyzed using the Mann-Whitney U test. Categorical variables were analyzed by χ test or Fisher exact test as appropriate.@*RESULTS@#Our study enrolled 109 COVID-19 patients who died during hospitalization and 116 recovered patients. The median age of the death group was older than the recovered group (69 [62, 74] vs. 40 [33, 57] years, Z = 9.738, P < 0.001). More patients in the death group had underlying diseases (72.5% vs. 41.4%, χ = 22.105, P < 0.001). Patients in the death group had a significantly longer time of illness onset to hospitalization (10.0 [6.5, 12.0] vs. 7.0 [5.0, 10.0] days, Z = 3.216, P = 0.001). On admission, the proportions of patients with symptoms of dyspnea (70.6% vs. 19.0%, χ = 60.905, P < 0.001) and expectoration (32.1% vs. 12.1%, χ = 13.250, P < 0.001) were significantly higher in the death group. The blood oxygen saturation was significantly lower in the death group (85 [77, 91]% vs. 97 [95, 98]%, Z = 10.625, P < 0.001). The white blood cell (WBC) in death group was significantly higher on admission (7.23 [4.87, 11.17] vs. 4.52 [3.62, 5.88] ×10/L, Z = 7.618, P < 0.001). Patients in the death group exhibited significantly lower lymphocyte count (0.63 [0.40, 0.79] vs. 1.00 [0.72, 1.27] ×10/L, Z = 8.037, P < 0.001) and lymphocyte percentage (7.10 [4.45, 12.73]% vs. 23.50 [15.27, 31.25]%, Z = 10.315, P < 0.001) on admission, and the lymphocyte percentage continued to decrease during hospitalization (7.10 [4.45, 12.73]% vs. 2.91 [1.79, 6.13]%, Z = 5.242, P < 0.001). Alanine transaminase (22.00 [15.00, 34.00] vs. 18.70 [13.00, 30.38] U/L, Z = 2.592, P = 0.010), aspartate transaminase (34.00 [27.00, 47.00] vs. 22.00 [17.65, 31.75] U/L, Z = 7.308, P < 0.001), and creatinine levels (89.00 [72.00, 133.50] vs. 65.00 [54.60, 78.75] μmol/L, Z = 6.478, P < 0.001) were significantly higher in the death group than those in the recovered group. C-reactive protein (CRP) levels were also significantly higher in the death group on admission (109.25 [35.00, 170.28] vs. 3.22 [1.04, 21.80] mg/L, Z = 10.206, P < 0.001) and showed no significant improvement after treatment (109.25 [35.00, 170.28] vs. 81.60 [27.23, 179.08] mg/L, Z = 1.219, P = 0.233). The patients in the death group had more complications such as acute respiratory distress syndrome (ARDS) (89.9% vs. 8.6%, χ = 148.105, P < 0.001), acute cardiac injury (59.6% vs. 0.9%, χ = 93.222, P < 0.001), acute kidney injury (18.3% vs. 0%, χ = 23.257, P < 0.001), shock (11.9% vs. 0%, χ = 14.618, P < 0.001), and disseminated intravascular coagulation (DIC) (6.4% vs. 0%, χ = 7.655, P = 0.006).@*CONCLUSIONS@#Compared to the recovered group, more patients in the death group exhibited characteristics of advanced age, pre-existing comorbidities, dyspnea, oxygen saturation decrease, increased WBC count, decreased lymphocytes, and elevated CRP levels. More patients in the death group had complications such as ARDS, acute cardiac injury, acute kidney injury, shock, and DIC.
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Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Betacoronavirus , C-Reactive Protein , Coronavirus Infections , Mortality , Oxygen , Blood , Pandemics , Pneumonia, Viral , Mortality , Retrospective StudiesABSTRACT
Objective:To develop and validate a predictive model for the differential diagnosis of diabetic nephropathy (DN) and non-diabetic renal disease (NDRD) in patients with type 2 diabetes mellitus.Methods:A retrospective study with patients with type 2 diabetes who underwent renal biopsy in the First Affiliated Hospital of Zhengzhou University from February 2012 to January 2015 was conducted. The dataset was randomly split into development (70.0%) and validation (30.0%) cohorts. Baseline predictors for model development was selected by using univariable and multivariable logistic regression. The model's performance in the two cohorts, including discrimination and calibration, was evaluated by the C-statistic, calibration curve and the P value of the Hosmer-Lemeshow test. Results:Among the 931 patients with type 2 diabetes, 478 cases (51.3%) diagnosed as DN alone, 214 cases (23.0%) as NDRD alone and 239 cases (25.7%) as DN plus superimposed NDRD (MIX). Among NDRD and MIX patients, membranous nephropathy was the most common pathological type, followed by IgA nephropathy. The variables selected in the final predictive model were age, duration of diabetes, diabetic retinopathy, systolic blood pressure, hemoglobin, fasting blood glucose, glycosylated hemoglobin, cystatin C. The model performed well with good discrimination and calibration. The C-statistics were 0.913(95% CI 0.892-0.935) in the derivation cohort and 0.897(95% CI 0.876-0.919) in the validation cohort. The model had the best P value of 0.934 of the Hosmer-Lemeshow test. Conclusions:A simple predictive model with high accuracy is constructed for predicting the presence of NDRD and MIX for type 2 diabetic patients. The nomogram can be used as a decision support tool to provide a non-invasive method for differential diagnosis of DN and NDRD, which may help clinicians assess the risk-benefit ratio of kidney biopsy for type 2 diabetic patients with renal impairment.
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Objective:To compare the prognosis of hemodialysis (HD) and peritoneal dialysis (PD) in end-stage renal disease (ESRD) patients without diabetes mellitus and identify related influencing factors.Methods:Patients who started hemodialysis with an arteriovenous graft or fistula or PD in the First Affiliated Hospital of Zhengzhou University from January 1, 2013 to February 1,2019 were included. They were followed up until May 1, 2019. The patients were divided into HD group and PD group according to the initial dialysis modality. Kaplan-Meier method was used to obtain survival curves, the Cox regression model was used to evaluate influence factors for survival rates, and the inverse probability of treatment weighting (IPTW) was used to eliminate influence of the confounders in the groups.Results:There were 371 patients with maintenance dialysis enrolled in this study, including 113 cases (30.5%) in HD group and 258 cases (69.5%) in PD group. At baseline, the scores of standard mean difference ( SMD) in age, body mass index (BMI), combined with cerebrovascular disease, Charlson comorbidity index (CCI), blood potassium, plasma albumin and hemoglobin between the two groups were greater than 0.1. The score of SMD decreased after IPTW, and the most data were less than 0.1, which meant that the balance had been reached between the two groups. The Kaplan-Meier survival curve showed that the cumulative survival rates had no significant difference for all-cause death before using IPTW between the two groups (Log-rank χ2=0.094, P=0.759). After adjusting for confounders with IPTW, the Kaplan-Meier survival curve showed that the cumulative survival rates still had no significant difference for all-cause death between the two groups (Log-rank χ2=2.090, P=0.150). Univariate Cox regression analysis showed that there was no significant difference between HD and PD on survival rates in ESRD patients without diabetes mellitus for all-cause death (PD/HD, HR=1.171, 95% CI 0.426-3.223, P=0.760). Multivariate Cox regression analysis showed that there was no significant difference between HD and PD on survival rates in ESRD patients without diabetes mellitus (PD/HD, HR=1.460, 95% CI 0.515-4.144, P=0.477), and high plasma albumin ( HR=0.893, 95% CI 0.813-0.981, P=0.019) was an independent protective factor for survival in ESRD patients without diabetes mellitus. There was still no significant difference between HD and PD on survival rates in ESRD patients without diabetes mellitus after using IPTW (PD/HD, HR=1.842, 95% CI 0.514-6.604, P=0.348). Conclusion:The difference of cumulative survival rates between HD and PD is not significant in ESRD patients without diabetes mellitus.
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Systemic inflammatory reaction – due to severe response to toxins of infection associated with immune inhibition – leads to multi-organ dysfunctions and high mortality. Ultraviolet (UV) blood is used for its therapeutic effects when moving across the cells. This study aims to evaluate the impact of UV-C Haematogenous Oxidation Therapy (HOT) in Lipopolysaccharide (LPS)-induced endotoxemia of rabbit model. A total of 40 rabbits randomly divided into four groups, including normal control (NC). LPS and LPS+UV-C HOT groups received 0.1 mg/kg LPS toxin of E. coli, UV-C HOT and LPS+UV-C HOT groups subjected to UV-C HOT treatments once weekly for five times. Blood collected, perfused with oxygen, UV-C directly irradiated into blood, and then auto-transfused. Rabbits were sacrificed after five weeks; blood and serum were collected for analysis. The survival rate, liver, kidney, lipid profile, and blood ions were assessed in treated rabbits. Mortality was 40% in the LPS group, while other groups showed no death. UV-C HOT enhanced critical pH, base deficit, blood gases, hypomagnesemia, hyperlactatemia, and concurrent acidosis. Besides, TNF-α, nitrite, and nitrate were suppressed in response to UV-C HOT. Moreover, UV-C HOT reduced liver and kidney enzymes, improved lipid metabolism, and ameliorated electrolytes homeostasis. Despite that, UV-C HOT performance in ICU for human and animal endotoxemic or septic patients should be evaluated and considered.
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Objective@#To investigate the prognostic relationship between the expression levels of periostin (POSTN) in hepatocellular carcinoma (HCC) tissues as well as its effect in invasion and metastasis.@*Methods@#The expression levels of POSTN in liver cancer tissues were detected with real-time quantitative PCR (QPCR) and immunohistochemistry (IHC). Kaplan-Meier method and Log-rank test were used to analyze the relationship between POSTN expression level and postoperative prognosis in patients with liver cancer. The expression of POSTN in hepatocellular carcinoma cells with different metastasis characteristics were detected in vitro and the overexpression of POSTN in low metastatic hepatocellular carcinoma cells was mediated through plasmid transfection techniques. The effects of POSTN on invasion and metastasis of hepatocellular carcinoma cells were determined by transwell migration and matrigel invasion assay. The comparative expression level of POSTN was analyzed by t-test.@*Results@#The expression levels of POSTN in tissues from high to low was in the order of metastatic liver cancer tissues, non-metastatic liver cancer tissues and normal liver tissues (P = 0.006). The median survival time and 3-year survival rate in postoperative patients with hepatocellular carcinoma of high POSTN expression level were significantly lower than the low expression group (10.00 months, 44.44%; 59.00 months, 53.13%, P = 0.031 2). In in vitro testing, the expression of POSTN was highest in MHCC97H cells with high metastatic characteristics as compared with Huh7 and MHCC97L cells with low and medium metastatic characteristics. After overexpression of POSTN in MHCC97L cells, the migration and invasion capacity of MHCC97L cells was increased.@*Conclusion@#POSTN is associated with pathological processes such as metastasis and invasion of liver cancer, which may promote the migration and invasion of liver cancer cells. It is expected to be an important prognostic biomarker of tumor recurrence and a therapeutic target for inhibiting the occurrence of metastasis in postoperative patients with hepatocellular carcinoma.
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Objective To compare the application value between PET/CT and PET/MR in diagnosing primary cervical cancer and pelvic lymph node metastasis.Methods Forty cases of cervical cancer were prospectively enrolled.PET/CT and PET/MR examinations were performed before treatment.All imaging data were evaluated by two experienced radiologists.The diagnostic consistency and difference of PET/CT and PET/MR were evaluated with Cohen's Kappa and paired Chi-square test.ROC curve was adopted to observe the value in diagnosing pelvic lymph node metastasis of cervical cancer.The lesions' visibility and diagnostic confidence of metastatic lymph nodes on PET/CT and PET/MR images were compared with Wilcoxon signed ranks test.Results Compared with the gold standard,the diagnostic consistency of PET/MR staging was much higher than that of PET/CT (x2 =10.286,P=0.002).The area under ROC curve of PET/CT and PET/MR on lymph node metastasis had no significant difference (Z=0.83,P＞0.05).No significant differences in lesion visibility between PET/CT and PET/MR images were detected in the evaluation of metastatic lymph nodes (P=0.157),while PET/MR revealed higher values regarding diagnostic confidence (P=0.014).Conclusion Both PET/CT and PET/MR provide high diagnostic value in detecting primary cervical cancer,but PET/MR has greater diagnostic superiority in the correct identification of cervical cancer stage and pelvic lymph node metastasis.PET/MR is expected to be a new technique for replacement of PET/CT in evaluation of cervical lesions.
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Objective@#To investigate the relationship between miRNA-196b-5p and miRNA-99a-5p expression and autophagy and apoptosis in multiple myeloma cells.@*Methods@#Human myeloma cell line U266 and normal CD138+ plasma cells were selected as the research objects. The subjects were divided into 45 cases of multiple myeloma patients and 40 healthy controls. The expression of miRNA-196b-5p and miRNA-99a-5p was measured by real-time quantitative PCR, and Western blot was used to determine the expression of autophagy related protein LC3-Ⅱ, LC3-Ⅰ, P62, Beclin-1 expression, apoptosis related protein CL caspase3, CL caspase7, Bcl-2, Bax, and TGF-β/Smad pathway associated proteins TGF-β1, Smad2/3, p-Smad3 and Smad7. The cell apoptosis rate was determined by flow cytometry. The correlation between miRNA expression level and clinical characteristics of multiple myeloma patients was analyzed.@*Results@#Compared with normal plasma cells, the expression of miRNA-196b-5p in myeloma cells increased significantly (0.43±0.15 vs 2.44±0.63 or 2.02±0.85, all P<0.001), the expression of miRNA-99a-5p was significantly decreased (1.87±0.61 vs 0.62±0.15 or 0.80±0.33, P<0.001), LC3-Ⅱ/LC3-Ⅰ increased significantly (P<0.05), Beclin-1 expression increased significantly (P<0.05), P62 expression decreased significantly (P<0.05). The expression of Bax, CL caspase3 and CL caspase7 decreased significantly (P<0.05), and the expression of Bcl-2 increased significantly (P<0.05) and apoptosis rate significantly decreased (P<0.05). After transfected with miRNA-196b-5p mimic or miRNA-99a-5p inhibitor, the LC3-Ⅱ/LC3-Ⅰ of CD138+ plasma cells increased significantly (P<0.05), the expression of Beclin-1 increased significantly (P<0.05), P62 expression decreased significantly (P<0.05), and the apoptosis rate significantly decreased (P<0.05). However, after autophagy inhibitor of 3-MA was administered, the apoptotic rate of the above reaction system did not change significantly (P>0.05). The expression of miRNA-196b-5p and miRNA-99a-5p was significantly correlated with DS and ISS stage in multiple myeloma patients (P<0.05).@*Conclusion@#miRNA-196b-5p and miRNA-99a-5p are closely related to the clinical characteristics of patients with multiple myeloma. The overexpression of miRNA-196b-5p and down regulation of miRNA-99a-5p could inhibit the apoptosis of myeloma cells by up regulation of autophagy, and the mechanism is related to the activation of the TGF-β/Smad signaling pathway.
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Objective@#To investigate the surgical treatment of infectious diseases of the breast.@*Methods@#The clinical data of 75 patients with breast infectious diseases who underwent surgery were reviewed and summarized.@*Results@#Of 75 cases, there were 20 cases of acute lactation mastitis, 50 cases of non-lactation mastitis, 2 cases of infection after tumor breaking, 2 cases of infection after surgery or trauma, 1 case of tuberculosis of breast.Operation was the main treatment method, and drug was also used for clinical treatment.40 cases underwent lesionectomy, 28 cases with severe inflammation and abscess formed underwent incision and drainage of abscess, 5 cases with sinus underwent lesion and sinus resection, 2 cases were diagnosed with cancer and got modified radical mastectomy.@*Conclusion@#The infectious diseases of the breast have complex and varied clinical manifestations, which include many kinds of breast diseases, and are easy to be misdiagnosed, and operation is an effective way for treatment, but should be combined with other treatment based on specific condition to achieve better curative effect.
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Objective: To investigate the expression of heat shock protein 27 (HSP27) in multiple myeloma (MM) cells, and to explore its relationship with bortezomib (BTZ) resistance. Methods: The expression levels of HSP27 mRNA and protein in myeloma cells (CD38+/CD138+ plasma cells) of 22 patients with MM (12 newly treated patients and 10 relapsed patients after BTZ treatment) were detected by real-time fluorescent quantitative PCR and Western blotting, respectively. The BTZresistant U266/BTZ cell line was established, and CCK-8 assay was used to detect the effects of different concentrations of BTZ, doxorubicin and etoposide on the proliferation of U266/BTZ cells and the parent U266 cells. The expression levels of HSP27 mRNA and protein in U266/BTZ cells and U266 cells were also examined by real-time fluorescent quantitative PCR and Western blotting, respectively. The specific small interfering RNA (siRNA) was used to silence HSP 27 gene expression in U266/BTZ cells, and the impact of silencing HSP 27 gene expression on BTZ-induced apoptosis of U266/BTZ cells was assessed by FCM. Additionally, the U266 cells were treated with BTZ alone or in combination with p38 mitogen-activated protein kinase (MAPK) signaling pathway inhibitor SB203580, then the expression levels of HSP27, phospho-HSP27 (p-HSP27), p38 MAPK, and p-p38 MAPK were measured by Western blotting. Finally, the recombinant lentivirus pCDH-CMV-MCS-EF1-copGFP-T2A-Puro/ HSP27 was constructed and infected into U266 cells to induce the overexpression of HSP 27 gene, then the activity of 20S proteasome in U266 cells with HSP 27 gene overexpression after treatment with different concentrations of BTZ was determined by fluorescence substrate method. Results: The expression levels of HSP27 mRNA and protein in myeloma cells from MM-relapsed patients were significantly higher than those in newly treated patients (both P < 0.01). BTZ-resistant myeloma cell line was successfully established, the half-maximal inhibitory concentration (IC50) of BTZ, doxorubicin and etoposide in BTZ-resistant U266/BTZ cells was significantly increased as compared with its parent U266 cells (all P < 0.01). The expressions of HSP27 mRNA and protein in U266/BTZ cells were significantly up-regulated (both P < 0.01). Silencing HSP 27 gene expression significantly increased BTZ-induced apoptotic rate of U266/BTZ cells (P < 0.01). Treatment with BTZ alone considerably up-regulated the expressions of HSP27, p-HSP27 and p-p38 MAPK in U266 cells, while this effect could be dramatically counteracted by pre-treatment with SB203580 (all P < 0.01). Furthermore, the overexpression of HSP 27 gene significantly reduced the inhibitory effects of BTZ at different concentrations on the activity of 20S proteasome in U266 cells (P < 0.01). Conclusion: The expression of HSP27 is closely related to BTZ-resistance of MM cells, which may be related to the BTZ exposure activating the p38 MAPK signaling pathway and up-regulating HSP27 expression, consequently decreasing the inhibitory effect of BTZ on proteasome activity through a feedback mechanism.
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Objective To investigate the diagnosis and treatment of mammographic calcifications found by mammary molybdenum target inspection.Methods 150 women who were found out with breast calcifications by mammary molybdenum target inspection and had been treated with surgical excision biopsy were selected.Their clinical data were retrospectively analyzed.Results In 150 cases of mammographic calcifications,102 cases were benign lesions by pathologic diagnosis,and 48 cases were malignant.Compared the morphological characteristics of the benign and malignant breast calcifications,the nature of the lesion was associated with lesion size (x2 =5.55),the density of calcification (x2 =7.591) and the distribution of calcifications (x2 =11.859).Conclusion Mammographic calcifications found by mammary molybdenum target inspection has a certain clinical value for diagnosis and treatment of breast cancer,so such patients should be encouraged to do biopsy to diagnose or exclude breast cancer.
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[Objective] To investigatethe correlation between blood flow signal on three dimensional time-of-flight magnetic resonance angiography (3D-TOF-MRA) and short-term outcome in patients with symptomatic middle cerebral artery (MCA) severe stenosis or MCA occlusion.[Methods] We retrospectively reviewed consecutive patients with symptomatic MCA severe stenosis or MCA occlusion.General information,clinical data and cranial imaging data were collected.Characteristics of blood flow signal on 3D-TOF-MRA for each patient were analyzed,which included:(1) blood flow signal of MCA distal to stenosis/occlusion lesion;(2) laterality of posterior cerebral artery (PCA).The correlation between characteristics of blood flow signal and short-term outcome was analyzed.[Results] Three hundred and twenty-eight patients were included in this study.There were 154 patients with symptomatic MCA severe stenosis and the rest of them had symptomatic MCA occlusion.Poor blood flow signal of distal MCA independently correlated with poor shortterm outcome in patients with severe MCA stenosis.[Odds Ratio (OR) 0.32,95％ Confident Interval (CI) 0.14～0.72].PCA laterality was not related with short-term outcome in these patients (OR,2.28,95％ CI,0.85～6.15).PCA laterality independently correlated with poor short-term outcome in patients with MCA occlusion.(OR,3.54,95％ CI,1.32～ 9.78).Blood flow signal of distal MCA was not related with short-term outcome in these patients (OR,0.58,95％ CI,0.22～1.48).[Conclusion] Blood flow signal on 3D-TOF-MRA correlates with short-term outcome in patients with symptomatic MCA severe stenosis or occlusion but the characteristics differs between severe MCA stenosis and occlusion patients.Anterograde blood flow (blood flow signal of MCA distal to stenosis lesion) for patients with severe MCA stenosis and retrograde blood flow (PCA laterality) for patients with MCA occlusion correlates with shot-term outcome.
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Objective To observe the expression of NOD2 and epithelial-mesenchymal transition (EMT) related proteins in podocytes in high glucose environment,and explore the molecular mechanism of NOD2 involved in EMT.Methods The human glomerular podocytes were the subjects of study.α-SMA and Nephrin expressions were detected by immunofluorescence;the mRNA and protein expressions of NOD2,Snail and EMT related proteins (α-SMA,Desmin,E-cadherin,Nephrin) were detected by real-time fluorescence quantitative PCR and Western blotting.The podocytes were stimulated by high-glucose after shRNA interfering the of NOD2 expression,and the expressions of Snail and subsequent EMT-related proteins were detected by Western blotting.Prior to the activation of NOD2 by muramyl dipeptide (MDP),shRNA was used to interfere with the expression of Snail.E-cadherin,Nephrin,Desmin,and α-SMA were detected by Western blotting.Results After 24 hours of high glucose stimulation,PCR and Western blotting results showed that the expressions of NOD2 and Snail were significantly increased;the expressions of epithelial phenotype proteins E-cadherin and Nephrin were down-regulated;and the expressions of interstitial phenotype proteins Desmin and α-SMA were increased (all P ＜ 0.05);while there was no significant change in the hypertonic control group.After interference with NOD2,the abnormal expression of Snail and EMT related proteins were all recovered.After interference with Snail expression,Compared with the MDP group,the protein expressions of E-cadherin and Nephrin were significantly increased (all P ＜ 0.05);the expressions of Desmin and α-SMA were significantly decreased.Conclusions High glucose can induce NOD2 expression in podocytes,and promote podocyte epithelial-mesenchymal transition by upregulating Snail expression.Gene intervention targeting the NOD2/Snail/EMT pathway can reduce high-glucose-induced podocyte injury and may provide new ideas for the treatment of diabetic nephropathy.
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Objective To observe the expression of ChemR23 induced by Angiotensin Ⅱ (Ang Ⅱ) in podocyte and its role in renal injury.Methods Conditionally immortalized mice podocytes were cultured in vitro.Immunofluorescence was used to observe the sub-cellular location of ChemR23.The expressions of ChemR23,Nephrin and Podocin stimulated by different concentrations of Ang Ⅱ were detected by qRT-PCR and Western blotting.Lentivirus targeting ChemR23 was used.The expressions of Nephrin and Podocin and the phosphorylation state of NF-κB P65 were detected by Western Blot.The inhibitor of NF-κB P65 was added to the cultural medium for 2 h before Ang Ⅱ stimulation.The effect of NF-κB P65 inhibitor on Ang Ⅱ-induced expression of Nephrin and Podocin was detected by Western Blot.Results It is showed that ChemR23 was located in cytosol and membrane.Compared with the normal control,the expression of ChemR23 was significantly increased by Ang Ⅱ in mRNA and protein level,while the expressions of Nephrin and Podocin were decreased (P ＜ 0.05).When using Lentivirus vector to interfere the expression of ChemR23,Ang Ⅱ-repressed expressions of Nephrin and Podocin were restored (P ＜ 0.05).Western Blot showed the level of phosphorylated NF-κB P65 was significantly increased by Ang Ⅱ stimulation (P ＜ 0.05),which could be inhibited by interfering the expression of ChemR23.When adding the NF-κB P65 inhibitor,the low expression of Nephrin and Podocin induced by Ang Ⅱ stimulation was restored (P＜0.05).Conclusions Ang Ⅱ can induce ChemR23 expression,which activates NF-κB P65 signaling pathway,and then inhibits the expressions of Nephrin and Podocin.Targeting ChemR23 is a potential way to alleviate podocyte injury caused by Ang Ⅱ.
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Objective To examine the practical value of early detection of heart-type fatty acid binding protein (H-FABP)for risk stratification and prognosis assessment in cardiac troponin T (cTnT)-negative acute coronary syndrome(ACS)patients.Methods From March 2010 to March 2012,55 patients with chest pain and negative cTnT were selected from 232 ACS patients at the General Hospital of PLA.Expression levels of cTnT and H-FABP were detected within 6 h of the onset of clinical symptoms.H-FABP and cTnT values at 12,24,and 48 h from the onset of clinical symptoms were continuously measured to monitor the dynamic changes.Based on prognosis,patients were divided into two groups,levels of H-FABP were compared,and its predictive value for prognosis was assessed with the ROC curve.Results Within 6 h of the onset of clinical symptoms,cTnT levels in cTnT-negative ACS patients increased gradually as disease progressed and reached the peak value at 12 h before decreasing slowly and arriving at 50％ of the peak value at 48 h.Meanwhile,HFABP levels reached the peak within 6 h,decreased slightly(12.8％) at 12 h,and then decreased rapidly at 48 h (about 79％).Of 55 patients,24 had acute myocardial infarction during hospitalization.The H-FABP level within 6 h was a good predictor for cTnT-negative ACS patients.The area under ROC curve was 0.946 and the cutoff value was 15.47 μg/L.The prediction sensitivity was 87.5 ％,with a specificity of 90.3％.Eleven patients had cardiovascular events after a 12-month follow-up.Levels of H-FABP were different in patients with or without cardiovascular events,[(38.08±8.43) μg/L vs.(18.96 ± 2.85) μg/L (t =2.438,P＜0.05)].ROC curve analysis showed that the area under the curve was 0.772 and the prediction cutoff value was 44.71 μg/L.The rates of cardiovascular events were markedly different between patients with high(≥44.71 μg/L)and those with 1ow(＜44.71 μg/L)H-FABP levels(54.5％ vs.11.4％).Conclusions For ACS patients with negative cTnT,H-FABP is a good index for early risk stratification and prognosis assessment.
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OBJECTIVE@#To investigate relationship of miRNA-132, miRNA-256, miRNA-143 and miRNA-145 level with antophagy and apoptosis of multiple mgeloma cells.@*METHODS@#Human myeloma cell line U266 and normal CD138 plasma cells were selected and used for study and detection, the 45 cases of MM were enrolled in MM group, and 40 normal persons were sellectod in control group. The expression of miRNA-132, miRNA-125b, miRNA-143 and miRNA-145 were measured by using qPCR, the expressions of autophagy-related protein (LC3-Ⅱ, LC3-Ⅰ, P62, beclin-1) and apoptosis-related molecules (cleaved-Caspase3, cleaved-Caspase7, BCL-2, BAX) were measured by using Western blot, respectively. The rate of apoptosis was measured by using flow cytometry. The correlation of miRNA expression level with clinical-related indexes including M protein, hemoglobin, β2-MG, lactate dehydrogenase, albumin, creatinine and serum calcium was analyzed.@*RESULTS@#Compared with normal plasma cells, the expression of miRNA-132 and miRNA-125b in myeloma cells increased significantly (P0.05). The expressions of miRNA-132, miRNA-125b, miRNA-143 and miRNA-145 were significantly different between DS and ISS staging group, also between the patients with abnormal and normal chromosome karyotype (P<0.05). The miRNA-125b and miRNA-143 significantly correlated with the levels of β2-MG, albumin and hemoglobin (P<0.05).@*CONCLUSION@#The expressions of miRNA-132, miRNA-125b, miRNA-143 and miRNA-145 in patients with multiple myeloma closely relate with the clinical characteristics. Both over-expression of miRNA-125b and down-expression of miRNA-143 inhibit the apoptosis of myeloma cells by up-regulation of autophagy.
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Humans , Apoptosis , Autophagy , Beclin-1 , Cell Line, Tumor , MicroRNAs , Multiple MyelomaABSTRACT
Rapid development of MRI has gradually evolved from morphological imaging to functional imaging.Functional MRI can provide pathophysiological information more than morphological information,such as molecular and metabolic information.The application value of functional MRI in cervical cancer has become a hotspot in recent years.The research progresses of functional MRI in cervical cancer were reviewed in this article.
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Rapid development of MRI has gradually evolved from morphological imaging to functional imaging.Functional MRI can provide pathophysiological information more than morphological information,such as molecular and metabolic information.The application value of functional MRI in cervical cancer has become a hotspot in recent years.The research progresses of functional MRI in cervical cancer were reviewed in this article.
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Objective To observe the role and related mechanism of chemerin and its receptor ChemR23 in glomerular endothelial cells (GEnCs) stimulated by high glucose.Methods Mouse GEnCs were cultured and divided into control group,20.0 mmol/L high glucose group,40.0 mmol/L high glucose group and mannitol control group.Then the expressions of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in cell culture supematant as well as the expressions of intracellular protein and mRNA of chemerin,ChemR23,IL-6 and TNF-α were detected.Lentiviral transfection targeting ChemR23 was applied before high glucose-or Chemerin-stimulated,and expressions of supernatant and intracellular mRNA of IL-6 and TNF-α were measured.Meanwhile whether p38 mitogen-activated protein kinase (p38 MAPK) pathway was activated by high glucose was detected.The specific inhibitor of p38 MAPK was added prior to high glucose-stimulated,then supernatant and intracellular mRNA expressions of IL-6 and TNF-α was detected.The supernatant expressions of IL-6 and TNF-α were measured by ELISA.The intracellular protein expression and p38 MAPK phosphorylation activity were detected by Western blotting.The mRNA expression was detected by real time PCR.Results Compared with those in the control group,in high glucose groups the expressions of IL-6,TNF-α and chemerin were significantly increased (all P ＜ 0.05),however,the expressions of ChemR23 did not change (all P ＞ 0.05);the supernatant and mRNA expressions of IL-6 and TNF-α were also elevated in the chemerin group (all P ＜ 0.05).Lentivirus baring shRNA could efficiently suppress ChemR23 expression,and the Chemerin-or high glucose-induced expressions of IL-6 and TNF-α were reduced (all P ＜ 0.05).Also it could significantly reduce the expression of phosphorylated-p38 MAPK (p-p38 MAPK) induced by high glucose (P ＜ 0.05),as high glucose group had higher p-p38 MAPK than control group (P ＜ 0.05).While the high glucose-elevated expressions of IL-6 and TNF-α were significantly attenuated by p38 MAPK inhibitor (all P ＜ 0.05).Conclusions High glucose stimulation can induce the expression of chemerin in GEnCs.By binding to ChemR23,chemerin activates p38 MAPK signaling pathway,and then promotes the expressions of IL-6 and TNF-α.These inflammatory cytokines aggravate inflammation of GEnCs.
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OBJECTIVE@#To investigate the protective effects of Nigella sativa seed extract (NSSE) against acetaminophen (APAP)-induced hepatotoxicity in TIB-73 cells and rats.@*METHODS@#Toxicity in TIB-73 cells was induced with 10 μmol/L APAP and the protective effects of NSSE were evaluated at 25, 50, 75, 100 μg/mL. For in vivo examination, a total of 30 rats were equally divided into five experimental groups; normal control (vehicle), APAP (800 mg/kg body weight single IP injection) as a hepatotoxic control, and three APAP and NS pretreated (2 weeks) groups (APAP + NSSE 100 mg; APAP + NSSE 300 mg and APAP + NSSE 900 mg/kg).@*RESULTS@#TIB-73 cell viability was drastically decreased by (49.0 ± 1.9)% after the 10 μmol/LAPAP treatment, which also increased reactive oxygen species production. Co-treatment with NSSE at 25, 50, 75, and 100 μg/mL significantly improved cell viability and suppressed reactive oxygen species generation. In vivo, the APAP induced alterations in blood lactate levels, pH, anionic gap, and ion levels (HCO3(-), Mg(2+) and K(+)), which tended to normalize with the NSSE pretreatment. The NSSE also significantly decreased elevated serum levels of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and alkaline phosphatase induced by APAP, which correlated with decreased levels of hepatic lipid peroxidation (malondialdehyde), increased superoxide dismutase levels, and reduced glutathione concentrations. Improved hepatic histology was also found in the treatment groups other than APAP group.@*CONCLUSIONS@#The in vitro and in vivo findings of this study demonstrated that the NSSE has protective effects against APAP-induced hepatotoxicity and metabolic disturbances by improving antioxidant activities and suppressing both lipid peroxidation and ROS generation.