Efficacy analysis of blinatumomab in treatment of relapsed/refractory B-cell acute lymphoblastic leukemia / 白血病·淋巴瘤

Objective:To explore the efficacy and safety of blinatumomab in treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL).Methods:The data of 8 patients with relapsed/refractory B-ALL treated with blinatumomab in Shanghai Zhaxin Traditional Chinese and Western Medicine Hospital from September 2020 to December 2021 were retrospectively analyzed, and their clinical characteristics, overall survival, lymphocyte subsets, cytokines, tandem transplantation and adverse reactions were analyzed.Results:The median follow-up time of 8 patients was 143 d (range: 41-534 d). Five of the 8 patients were alive; among them, 4 of 6 patients assessed to be in minimal residual disease (MRD)-negative complete remission (CR) and 1 of 2 patients assessed to be in non-remission at the time of belintuzumab discontinuation were alive. The median duration of treatment with belintuzumab was 28 d (10-56 d), and it was 23 d (10-56 d) for patients with MRD-positive at baseline and 28 d (25-31 d) for the 4 non-remission patients. Six patients achieved MRD-negative CR after treatment, of which 4 were assessed as MRD-positive at baseline and 2 were assessed as non-remission at baseline. All 4 patients with MRD-positive CR achieved MRD-negative CR after treatment with belintuzumab, including 1 patient with Philadelphia chromosome-positive (Ph +) ALL bridged to autologous hematopoietic stem cell transplantation, and 1 patient with Ph + ALL and 1 patient with Ph - ALL received sequential allogeneic hematopoietic stem cell transplantation and had persistent MRD-negative CR. Two of the 4 non-remission patients achieved MRD-negative CR after treatment with belintuzumab, including 1 patient with Ph + ALL bridged to autologous hematopoietic stem cell transplantation, and 1 patient with Ph - ALL received sequential allogeneic hematopoietic stem cell transplantation, and the 2 patients had persistent MRD-negative CR. Leukocyte counts and neutrophils decreased in both MRD-positive CR and non-remission patients after receiving belintumomab. The proportion and absolute number of CD3 + T and CD3 + CD8 + T lymphocytes in patients with MRD-positive CR were higher than those in patients without remission, and both decreased after drug administration. Median interleukin-6 (46.23, 1.42 pg/ml), interleukin-8 (17.85, 2.10 pg/ml), interleukin-10 (7.43, 1.49 pg/ml) and interferon-γ (11.82, 0.39 pg/ml) levels were elevated in MRD-positive CR and non-remission patients at week 3 of treatment. Grade 1 cytokine release syndrome occurred in 1 case with clinical manifestations of fever, which improved after drug suspension. Three cases developed infections, 2 of which were pulmonary and 1 of which was upper respiratory tract infection. No immune effector cell-associated neurotoxic syndrome was observed. Conclusions:Belintumomab is effective for MRD clearance in relapsed/refractory B-ALL with manageable adverse reactions, providing an effective therapeutic option for bridging hematopoietic stem cell transplantation to prolong the survival of patients.

The role of methylation of placental glucocorticoid response gene in the association between pregnancy-related anxiety in the third trimester and birth outcomes / 中华预防医学杂志

Objective: To investigate the role of methylation of placental glucocorticoid response gene in the association between pregnancy-related anxiety in the third trimester and birth outcomes. Methods: Based on a prospective cohort study, singleton live births and their mothers from the Ma'anshan Birth Cohort Study (MABC) were included as participants in this study. The maternal pregnancy-related anxiety symptoms in the third trimester of pregnancy were evaluated by using the Pregnancy-related Anxiety Questionnaire. The neonatal birth outcomes were collected from medical records. The placental tissues from 300 pregnant women with pregnancy-related anxiety and 300 without pregnancy-related anxiety were collected to detect the methylation of FKBP5, NR3C1 and HSD11B2 genes using the Methyl Target approach. The methylation factors were extracted by exploratory factor analysis. Linear regression or logistic regression models were used to analyze the association between pregnancy-related anxiety in the third trimester, methylation factor scores, and birth outcomes. The mediating role of methylation factors in the association between pregnancy-related anxiety in the third trimester and birth outcomes was analyzed by using the Process procedure. Results: The mean age of 2 833 pregnant women was (26.60±3.60) years old. After adjusting for confounding factors, pregnancy-related anxiety in the third trimester increased the risk of small-for-gestational-age (OR=1.32, 95%CI:1.00-1.74). A total of 5 methylation factors were extracted, and the factor 5 was loaded with FKBP5 CpGs 18-21. Pregnancy-related anxiety in the third trimester was negatively correlated with the factor 5 (β=-0.24,95%CI:-0.44--0.05). The factor 5 was positively correlated with the gestational age (β=0.17, 95%CI:0.06-0.27). In addition, the factor 2 (β=0.02,95%CI:0.00-0.04) and factor 3 (β=0.03,95%CI:0.01-0.05) were positively correlated with 5-min Apgar score after delivery. However, this study did not found the mediating role of the scores of the factor characterized by FKBP5 in the relationship between pregnancy-related anxiety and birth outcomes. Conclusion: Pregnancy-related anxiety in the third trimester may reduce the methylation level of FKBP5 CpGs 18-21 in placental tissues and is associated with the risk of small-for-gestational-age.

The output efficiency of the National Science Foundation′s rehabilitation funding from 2009 to 2018 / 中华物理医学与康复杂志

Objective:To analyze and compare rehabilitation research funded by China′s National Natural Science Foundation (NSFC) with that funded by America′s National Institutes of Health (NIH) so as to provide references for future funding.Methods:Articles reporting rehabilitation research funded by the NSFC and the NIH were retrieved from the NSFC′s Science Output Service website and the NIH′s Project Report website and analyzed.Results:From 2009 to 2018 the NSFC funded 421 rehabilitation studies which resulted in a published report while the NIH funded 312. In 2018, the NSFC budget (US$3.89 million) was 8.46 times that of 2009 (US$460, 000), while the NIH′s grant budget (US$36.08 million) was 2.17 times that of 2009 (US$16.62 million). The number of published papers resulting from the Chinese and American studies was 1111 and 2571 respectively. Their impact factors mainly ranged between 0 and 3 points. Among the journals with an impact factor of 6 or more, published papers from the United States (297) were much more numerous than those from China (18). The number of SCI papers per million US dollars increased by 2.25 times in China and 0.05 times in the US.Conclusions:Both China and the United States have been investing more in rehabilitation medicine research, and that has resulted in more published papers. There is still a gap in funding and output between the two countries.

Association between inflammation activity of left atrial epicardial adipose tissue measured by 18F-FDG PET/CT and atrial fibrillation / 中华心血管病杂志

Objective: To explore the association between inflammation activity of left atrial epicardial adipose tissue (LA-EAT) measured by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and atrial fibrillation (AF). Methods: A total of 78 patients with AF, who underwent 18F-FDG PET/CT in the Nuclear Medicine Department of the Third Affiliated Hospital of Soochow University due to abnormally elevated levels of tumor indicators or malignant tumors from March 2018 to December 2019, were enrolled in this retrospective study. According to the examination date of PET/CT and basic characteristics of AF patients (gender, age), a 1∶1 propensity score matching was used to enroll a non-AF control group (78 patients). The maximum standard uptake value of left atrial epicardial tissue (LA-EAT FDG SUVmax) and total EAT volume (V-EAT) were measured by 18F-FDG PET/CT. Left ventricular ejection fraction (LVEF) and left atrial diameter (LAD) were obtained by echocardiography. Blood lipids and biomarkers of inflammation were measured. The differences of clinical data and EAT-related indicators were compared between the AF group and control group. Logistic multivariate regression analysis was used to determine the related factors of AF. Then the receiver operating characteristic (ROC) curve was used to determine the cutoff value of LA-EAT FDG SUVmax on the diagnosis of AF. Univariate and multivariate logistic regression analysis were used to analyze the relationship between the increase of LA-EAT FDG SUVmax and AF. Results: The age was (66.9±10.2) years and there were 55 males (70.5%) in the AF group. The age was (66.9±8.0) years, and there were 52 males (66.7%) in the control group (both P>0.05). The LAD ((44.2±5.8) mm vs. (35.4±4.4) mm), V-EAT ((122.1±42.0) cm3 vs. (91.6±34.5) cm3), and LA-EAT FDG SUVmax ((1.6±0.3) vs. (1.4±0.2)) values were significantly higher, while LVEF ((60.1±4.7)% vs. (63.9±2.9)%) was lower in the AF group than in the control group (P all<0.001). Multivariate logistic regression analysis showed that LAD (OR=1.340, 95%CI 1.195-1.502), V-EAT (OR=1.016, 95%CI 1.001-1.031), and LA-EAT FDG SUVmax (OR=1.375, 95%CI 1.095-1.723) were positively correlated with AF, LVEF (OR=0.781, 95%CI 0.659-0.926) was negatively correlated with AF(P all<0.05). The area under the ROC curve of LA-EAT FDG SUVmax for diagnosis of AF was 0.680 (95%CI 0.597-0.764, P<0.001), and the best cut-off value was 1.415 with a sensitivity of 65.4% and specificity of 61.5%. After adjusting for high-density lipoprotein cholesterol, LVEF, LAD and V-EAT, LA-EAT FDG SUVmax≥1.415 was independently associated with AF (OR=2.982, 95%CI 1.122-7.926, P=0.010). Conclusions: The inflammatory activity of LA-EAT measured by 18F-FDG PET/CT is an independent risk factor of AF, and the increased inflammatory activity of LA-EAT is positively correlated with AF.

Notch1 mediates breast cancer epithelial-mesenchymal transition through Slug / 西安交通大学学报(医学版)

Objective: To investigate the mechanism of Nocth1 in regulating epithelial-mesenchymal transition (EMT) in breast cancer. Methods: Jagged1 or shRNA was applied to regulate Notch signaling expression. EMT process and migration and invasion in breast cancer were determined. Moreover, Slug luciferase reporter assay was used to investigate the effect of Notch1 on Slug expression. And Slug expression was regulated by shRNA. The effects of Slug on Notch1 mediated breast cancer EMT process and migration and invasion were determined. Results: Jagged1 activated Notch signaling and promoted EMT process and migration and invasion in breast cancer. Overexpression of Notch1 could induce Slug promoter activation, and Slug overexpression could reverse the inhibition of Notch1 shRNA on breast cancer's EMT process and migration and invasion. Conclusion: Notch1 regulates EMT process, migration and invasion in breast cancer through targeting the Slug promoter.

Rehabilitation research supported by the NSFC between 2009 and 2018 / 中华物理医学与康复杂志

Objective:To investigate research into medical rehabilitation supported by China′s Natural Science Foundation (NSFC) between 2009 and 2018.Methods:Medical rehabilitation research projects supported by the NSFC between 2009 and 2018 were compiled. The project leaders, funding, awardee organization, research area and results were collected and analyzed.Results:There were 348 researchers who were supported in 421 projects during the period studied. They received ￥168.541 million and made 1395 achievements between 2009 and 2018. Neurological rehabilitation was the most popular research area, followed by musculoskeletal rehabilitation, while cardiopulmonary and pain rehabilitation were rarely covered.Conclusions:Rehabilitation medicine has been developed actively, but NSFC support has still been insufficient.

Outcomes of reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation for 10 patients with myelofibrosis / 中华血液学杂志

Objective@#To evaluate the efficacy of reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation (RIC-allo-HSCT) for patients with myelofibrosis (MF).@*Methods@#The clinical data of 10 patients with myelofibrosis (MF) who underwent RIC-allo-HSCT.@*Results@#Of all 10 patients, 6 were male and 4 women, with a median age of 28.5 (22-54). Using fludarabine/busulfan plus total body irradiation (FB+TBI) pretreatment scheme based. Hematopoiesis reconstitution was achieved in 9 patients (90%). The median time of neutrophil and platelet engraftment was 13.5 (10-22) day and 16.5 (13-40) day, respectively. Acute GVHD occurred in 4 cases while chronic GVHD in 5 cases. The prospective OS for 3 years was (90.0±8.5)% after a median follow-up time of 17 months. Transplant related mortality was 1 case.@*Conclusion@#RIC-HSCT with FB+TBI is a feasible and effective alternative for MF patients.

Clinical Study on Osteoporosis Treated by Taoshi Jiangu Decoction / 广州中医药大学学报

Objective To observe the therapeutic effect of Taoshi Jiangu Decoction for osteoporosis(OP). Methods A total of 120 cases of OP patients were randomly divided into treatment group and control group ,60 cases in each group. Patients in the treatment group were treated with Taoshi Jiangu Decoction orally,and those in the control group were treated with Caltrate D and Alendronate Sodium Tablets orally. Four weeks constituted one treatment course, and the treatment for the two groups covered 3 courses. The therapeutic effect of the two groups was evaluated by the changes of traditional Chinese medicine(TCM)syndrome scores,urine hydroxyproline (U-HYP),serum bone Gla-protein (BGP or osteocalcin),serum alkaline phosphatase (ALP),urine calcium (U-Ca),tartrate resistant acid phosphatase (TRAP), bone mass density(BMD) and quantitative CT(QCT) before and after treatment. Results (1)After treatment, the TCM syndrome scores of the two groups were decreased(P<0.05 compared with those before treatment),and the decrease in the treatment group was superior to that of the control group (P < 0.05). (2)After treatment,the levels of bone formation indexes of ALP and BGP were increased,and the levels of bone resorption indexes of U-HYP,U-Ca and TRAP were decreased in the two groups (P<0.05 compared with those before treatment). The effects of the treatment group were superior to those of the control group,the difference being statistically significant(P < 0.05).(3)After treatment,BMD of lumbar vertebrae 2-4 (L2-L4),neck of femur,Wards triangle and trochanter of femur,and QCT values of left neck of femur were obviously increased in the two groups (P < 0.05 compared with those before treatment). The treatment group showed stronger effect on increasing BMD and QCT values than the control group, the difference being statistically significant (P < 0.05). Conclusion Taoshi Jiangu Decoction can restrain bone absorption , promote bone formation and increase BMD, showing certain therapeutic effect for OP.

Clinical and epidemiological characteristics of multidrug-resistant Acinetobacter baumannii strains / 西安交通大学学报(医学版)

Objective To confirm the species of multidrug-resistant Acinetobacter baumannii (MRAB)strains collected from our hospital by specific PCR amplification,and further investigate their distribution,antibiotic resistance and molecular classification characteristics.Methods We collected 47 MRAB clinical strains which had been identified by VITEK-2 system,followed by species confirmation using specific primers sp2F,sp4F and sp4R through PCR amplification.Antibiotic resistance characteristics were detected using VITEK-2 system.And the homology of MRAB isolates was analyzed using multilocus sequence typing (MLST).Results We confirmed 46 out of 47 strains as A .baumannii .All of them were multidrug-resistant strains,and the majority of them were found in sputum samples from patients in intensive care units (ICUs).MLST analysis found 4 ST types,namely ST195,ST218,ST368 and ST208.The last two types had the closest genetic relationship.Conclusion SpecificPCR amplification is a rapid and accurate method to identify A .baumannii .The MRAB strains in our hospital are mainly distributed in ICUs and are susceptible to only a few antibiotics such as tigecycline.

Clinical and epidemiological characteristics of multidrug-resistant Acinetobacter baumannii strains / 西安交通大学学报(医学版)

Objective To confirm the species of multidrug-resistant Acinetobacter baumannii (MRAB)strains collected from our hospital by specific PCR amplification,and further investigate their distribution,antibiotic resistance and molecular classification characteristics.Methods We collected 47 MRAB clinical strains which had been identified by VITEK-2 system,followed by species confirmation using specific primers sp2F,sp4F and sp4R through PCR amplification.Antibiotic resistance characteristics were detected using VITEK-2 system.And the homology of MRAB isolates was analyzed using multilocus sequence typing (MLST).Results We confirmed 46 out of 47 strains as A .baumannii .All of them were multidrug-resistant strains,and the majority of them were found in sputum samples from patients in intensive care units (ICUs).MLST analysis found 4 ST types,namely ST195,ST218,ST368 and ST208.The last two types had the closest genetic relationship.Conclusion SpecificPCR amplification is a rapid and accurate method to identify A .baumannii .The MRAB strains in our hospital are mainly distributed in ICUs and are susceptible to only a few antibiotics such as tigecycline.

PEG-rhG-CSF for peripheral blood stem cell mobilization in patients with relapsed or refractory malignant lymphoma / 中国肿瘤临床

Objective:To compare the efficacy and costs of pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) and granulocyte colony stimulating factor (G-CSF) for hematopoietic stem cell mobilization and hematopoietic recovery after transplantation in patients with relapsed or refractory malignant lymphoma. Methods:From July 2014 to October 2016, 15 patients with malignant lymphoma using peripheral blood stem cell mobilization (PBSCM) for autologous peripheral stem cell transplantation (APBSCT) were treated in our institution and enrolled in the PEG-rhG-CSF group (experimental group). We analyzed data from other 15 patients with malignant lymphoma mobilized with G-CSF who were treated in our institution from January 2013 to August 2015 (control group). Results:Patients in both groups were successfully mobilized. The median amounts of CD34+cells collected in the experimental and control groups were 16.2×106/kg and 8.9×106/kg, respectively (P=0.414), and the median amount of mononuclear cell (MNC) was 12.4×108/kg and 9.9× 108/kg, respectively (P=0.519). In the experimental and control groups, the mean durations of mobilization were 10.66±1.45 and 9.33±1.83 days (P=0.234), the mean durations of neutropenia during mobilization were 4.20±2.17 and 3.80±2.04 days (P=0.608), the mean durations of absolute neutrophil count recovery after APBSCT were 10.14±1.29 and 10.93±2.69 days (P=0.327), and the mean durations of platelet recovery were 10.36±2.27 and 12.27±3.38 days (P=0.121). Mobilization and hematopoietic recovery after APBSCT were not significantly different between the two groups. The cost was lower in the experimental group than that in the control group (RMB 3,960 yuan versus RMB 11,479.3±2,401.3 yuan). Conclusion:High-dose chemotherapy combined with PEG-rhG-CSF is a promising, effective, and low-cost mobilization regimen for patients with relapsed or refractory malignant lymphoma.

Association analysis of genetic variant of rs13331 in PSD95 gene with autism spectrum disorders: A case-control study in a Chinese population / 华中科技大学学报（医学）（英德文版）

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by high heritability. Recently, autism, the most profound form of ASD, has been increasingly attributed to synaptic abnormalities. Postsynaptic density 95 (PSD95), encoding PSD protein-95, was found essential for synaptic formation, maturation and plasticity at a PSD of excitatory synapse. It is possibly a crucial candidate gene for the pathogenesis of ASD. To identify the relationship between the rs13331 of PSD95 gene and ASD, we performed a case-control study in 212 patients and 636 controls in a Chinese population by using a polymerase chain reaction-restriction fragment length polymerase (PCR-RFLP) assay. The results showed that in genetic analysis of the heterozygous model, an association between the T allele of the rs13331 and ASD was found in the dominant model (OR=1.709, 95% CI 1.227-2.382, P=0.002) and the additive model (OR=1.409, 95% CI=1.104-1.800, P=0.006). Our data indicate that the genetic mutation C>T at the rs13331 in the PSD95 gene is strikingly associated with an increased risk of ASD.

Early diagnostic value of circulating microRNA-1 on acute myocardial infarction in patients with chest pain / 中华危重病急救医学

Objective To evaluate the early diagnostic value of circulating microRNA-1 (miR-1) on acute myocardial infarction (AMI). Methods A prospective cohort study was conducted. The patients with chest pain admitted to the Second People's Hospital of Wuxi from November 2012 to June 2015 were enrolled. According to AMI diagnostic criteria, the patients were divided into AMI group and non-AMI group, and healthy individuals during the same period were served as heath controls. The venous samples of the onset patients were collected within 3 hours after admission. The plasma miR-1 was determined by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR), and the levels of plasma cardiac troponin I (cTnI) and MB isoenzyme of creatine kinase (CK-MB) were measured by electrochemiluminescence. The correlation between plasma miR-1 and cTnI as well as CK-MB was performed by Spearman analysis. The early diagnostic performance of plasma miR-1, cTnI, and CK-MB for AMI was estimated by receiver operating characteristic (ROC) curve analysis. Results There were 127 patients in AMI group, and 107 in non-AMI group, including 82 patients with angina pectoris, 2 with pulmonary embolism, 3 with aortic dissection, 2 with acute pericarditis, 3 with myocarditis, 13 with acute heart failure, and 2 with peptic ulcer. Ninety volunteers were served as healthy controls. There was no difference in clinical characteristics including gender and hyperlipidemia between AMI group and non-AMI group. The expressions of plasma miR-1, cTnI and CK-MB were significantly increased in AMI patients as compared with those of the healthy controls [miR-1 (2-ΔΔCt): 4.32±2.60 vs. 1.44±0.75 and 0.98±0.18, cTnI (μg/L): 3.23 (0.63, 10.70) vs. 0.02 (0.00, 0.17) and 0.00 (0.00, 0.00), CK-MB (U/L): 32.40 (14.20, 95.40) vs. 14.40 (11.20, 17.10) and 8.90 (8.28, 9.50), all P < 0.01]. The expression of plasma miR-1 had a significantly positive correlation with cTnI and CK-MB in AMI patients (r1 = 0.395, r2 = 0.490, both P < 0.000). It was demonstrated by ROC curve analysis that the area under ROC curve (AUC) for the diagnostic value of miR-1 on AMI was 0.905 [95% confidence interval (95%CI) = 0.860-0.950, P = 0.000], the sensitivity was 86.6%, and the specificity was 95.4%; the AUC for cTnI was 0.908 (95%CI = 0.870-0.946, P = 0.000), the sensitivity was 81.9%, and the specificity was 95.9%; the AUC for CK-MB was 0.795 (95%CI = 0.736-0.854, P = 0.000), the sensitivity was 63.0%, and the specificity was 92.9%. Conclusions Plasma miR-1 has the capacity in early diagnosis of AMI, superior to CK-MB, and equal to cTnI. It can provide additional diagnostic information beyond cTnI. The diagnostic accuracy for early AMI can be improved with the combination of plasma miR-1 and cTnI.

Association analysis of genetic variant of rs13331 in PSD95 gene with autism spectrum disorders: A case-control study in a Chinese population / 华中科技大学学报（医学）（英德文版）

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by high heritability. Recently, autism, the most profound form of ASD, has been increasingly attributed to synaptic abnormalities. Postsynaptic density 95 (PSD95), encoding PSD protein-95, was found essential for synaptic formation, maturation and plasticity at a PSD of excitatory synapse. It is possibly a crucial candidate gene for the pathogenesis of ASD. To identify the relationship between the rs13331 of PSD95 gene and ASD, we performed a case-control study in 212 patients and 636 controls in a Chinese population by using a polymerase chain reaction-restriction fragment length polymerase (PCR-RFLP) assay. The results showed that in genetic analysis of the heterozygous model, an association between the T allele of the rs13331 and ASD was found in the dominant model (OR=1.709, 95% CI 1.227-2.382, P=0.002) and the additive model (OR=1.409, 95% CI=1.104-1.800, P=0.006). Our data indicate that the genetic mutation C>T at the rs13331 in the PSD95 gene is strikingly associated with an increased risk of ASD.

Effect of vitamin E on renal suffering ischemia/reperfusion injury of rats model / 中国综合临床

Objective To investigate the effects of vitamin E (VE) on renal ischemia/reperfusion (I/R) injury of rats.Methods A total of 18 male Wistar rats were randomly divided into sham-operated group,I/R group,VE + I/R group,and each group of 6 rats.All the animals were killed at the end of 24 h of reperfusion.Nephridial tissue were examined by light microscopy,and the level of blood urea nitrogen(BUN) and serum creatinine (SCr) were measured.The protein expressions of tumor necrosis factor α (TNF-α) were detected by Western blotting.Results Compared with sham-operated group,tubulointerstitial pathological injury in I/R group was significantly aggravated,which was shown by HE and PAS stain.Compared with I/R group,the degree of morphological changes as well as renal dysfunction in VE + I/R group were obviously lessened.Meanwhile,the levels of BUN,SCr in I/R group,VE + I/R group were (10.13 ± 2.14) mmol/L and (7.67 ± 1.63) mmol/L,(80.33 ±7.15) μmol/L and (63.67 ±5.40) μ mol/L,significantly higher than those in shamed-operated group ((3.85 ± 0.21) mmol/L,(48.67 ± 3.61) μmol/L;P ＜ 0.05).And the level of BUN and SCr in VE + I/R group were significant lower than those in I/R group(P ＜0.05).Western Blotting showed that the protein expressions of TNF-α in VE + I/R group were obviously lower compared with those in group of I/R without VE treatment (P ＜ 0.05).Conclusion Vitamin E can attenuate over-expressions of TNF-α in kidney following I/R,thus protect against structural damages and renal dysfunction in I/R rat models.

Up-regulation of intermedin protects kidney from ischemia/reperfuston injury / 中华肾脏病杂志

Objective To investigate the effect of intermedin (IMD) on renal ischemia/ reperfusion (I/R) injury after the up-regulation of IMD. Methods A total of 24 healthy Wistar male rats were randomly divided into four groups,sham-operated group,I/R group,IMD gene transfection +I/R group and empty plamid +I/R group.All the animals were killed at the end of 24 h of reperfusion.Histological changes and renal function were estimated.The expression and site of IMD were determined by Immunohistochemistry method,semi-quantitative RT-PCR and Western blotting.The protein expressions of endothelin 1 (ET-1),tumor necrosis factor αt (TNF-α) were detected by Western blotting. Results Compared with sham-operated group,tubulointerstitial pathological injury was significant aggravated in I/R group (7.6±2.3) and empty plamid +I/R group (7.0±1.8),and such injury was improved in IMD+I/R group (1.5±0.8) (P＜0.05).Compared with I/R group and empty plamid +I/R group,the renal dysfunction of IMD +I/R group was obviously lessened [BUN:(7.73±1.03) mmol/L vs (10.13±2.14) mmol/L,(9.77±1.92) mmol/L; Scr:(58.50±3.27) μmol/L vs (80.33±7.15) μmol/L, (75.67±7.58) μmol/L,all P＜0.05].IMD expression was weak in the plasma of tubulointerstitial cells in sham-operated group,and was up-regulated in I/R group. Compared with I/R group, immunohistochemical IMD expression increased obviously (262.03±67.89 vs 175.57±48.06,P＜0.01).The mRNA expression of IMD in IMD+I/R group was up-regulated significantly by 60.7％,66.1％ and the protein expression of IMD in IMD+I/R group increased significantly by 51.4％,55.9％ as compared to I/R and empty plasmid +I/R group.Meanwhile,the protein expressions of ET-1 and TNF-αt in IMD+I/R group were obviously lower compared with those in I/R group (ET-1:0.08±0.02 vs 0.17±0.02; TNF-α:0.21±0.04 vs 0.35± 0.02,all P＜0.05). Conclusion IMD gene transfected into kidneys of rats prior to I/R surgery can attenuate the over-expressions of both ET-1 and TNF-o in I/R injured rat kidneys as well as the damages to the structure and function of the kidneys.

Protective mechanism of NALP3-siRNA on rat renal tubular epithelial cells from hypoxia/reoxygenation injury / 中华肾脏病杂志

Objective To explore the mechanism of protecting cells from hypoxia/ reoxygenation (H/R) injury by constructing specific small interference RNA (siRNA) to inhibit NALP3 expression in rat renal tubular epithelial cells (NRK-52E).Methods (1) To establish the H/R injury model of NRK-52E by regulating the pressure of N2 in incubator to hypoxia condition,the cells were cultured with hypoxia for 1 h and then with reoxygenation for 1 h,2 h,4 h,8 h,16 h and 24 h.The activity of lactae dehydrogenase (LDH) in the culture medium,cell count and cell viability,the expression of NALP3 were determined by biochemical method,trypan blue exclusion and Western blotting.(2) The siRNA was transfected into NRK-52E.The irrespective siRNA transfected group wasused as control.NALP3 expression was examined by Western blotting.(3) The cells were divided into 4 groups:control group,H/R group,irrespective siRNA transfected group and NALP3-siRNA transfected group.To establish the H/R injury model of NRK-52E by regulating the pressure of N2 in incubator to hypoxia condition,the cells were cultured with hypoxia for 1 h and then with reoxygenation for 4 h.And the expression of NALP3 was determined by Western blotting.(4)Cellular apoptosis was examined by Annexin V/PI staining and flow cytometry.NF-κB DNA binding activity,IκB-α,Bcl-2 and Bax expression were examined by EMSA and Western blotting.Results (1)Compared with the control group,the activity of LDH significantly increased,cell count and cell viability significantly decreased (all P＜0.05).The expression of NALP3 significantly increased and peaked at 4 h after H/R.(2)The specific siRNA could efficiently inhibit NALP3 expression in NRK-52E.Compared with the irrespective siRNA transfected group,the protein expression of NALP3 was significantly down-regulated in NALP3 siRNA transfected group (P＜0.05).(3)After hypoxia 1 h and reoxygenation 4 h,the activity of LDH and the expression of NALP3 increased.Compared with the irrespective siRNA transfected group,LDH concentration in media and the expression of NALP3 significantly decreased in NALP3-siRNA transfected group.(4)After hypoxia 1 h and reoxygenation 4 h,NF-κB DNA binding activity was increased,IκB-α phosphorylation and degradation,Bcl-2 and Bax were significantly up-regulated.However,compared with the irrespective siRNA transfected group,NF -κB DNA binding activity,IκB-α degradation and Bax/Bcl-2 were significantly decreased (P＜0.05) in NALP3-siRNA transfected group.At the same time,the ratio of apoptosis was significantly increased in three groups than that in control.Compared with the irrespective siRNA transfected group,the ratio of apoptosis in NALP3-siRNA transfected group was significantly decreased (P＜0.05).Conclusions H/R induces the expression of NALP3 in NRK-52E.The synthesized siRNA can inhibit the expression of NALP3 and protect NRK-52E from hypoxia/reoxygenation injury.The mechanism may be via inhibiting the activation of NF-κB,modulating expression of Bcl-2 and Bax,as well as decreasing cell apoptosis.

Effect of intermedin on the expressions of angiogenesis-related genes induced by renal ischemia reperfusion injury / 中华肾脏病杂志

Objective To investigate the effect of intermedin (IMD) on the expressions of angiogenesis-related genes induced by renal ischemia reperfusion injury (IRI).Methods Wistar rats were randomly divided into four groups: control group,IRI group,empty plasmid group and IMD plasmid group.One week after removing the right kidney,eukaryotic expression vector encoding rat IMD gene was transfected into the left kidney using an ultrasound-microbubble mediated system.Renal IRI model was induced by clamping left renal arteries for 45 minutes followed by reperfusion for 1 d,2 d,3 d,4 d,7 d and 14 d.The expressions of hypoxia inducible factor-1α (HIF-1o),vascular endothelial growth factor (VEGF) and angiopoietin receptor Tie-2 were examined by RT-PCR and Western boltting.Results Compared with control group,an increase in HIF-1α,VEGF and Tie-2 was observed in the IRI group at d 1,d 2 and d 3 (allP＜0.05).The expression of HIF-1o peaked at d 1 d(P＜0.05),while VEGF and Tie-2 at d 2 (P＜0.05),followed by a decrease that was similar to the control levels at d 4(P＞0.05).Compared with the IRI group,the expressions of HIF-1α,VEGF and Tie-2 of IMD group were much higher and all reached the peak at d 1 (P＜0.05),maintained at d 2-4 (P＜0.05),followed by a decrease at d 7(P＞0.05).The above indexes had no differences between empty plasmid group and IRI group(P＞0.05).Conclusions IMD pretreatment may play an important role in the process of repair and regeneration after renal ischemia reperfusion injury byimproving the expressions of angiogenesis-related genes(HIF-1α,VEGF and Tie-2) induced by renal ischemia reperfusion injury.

Effects of intermedin pretreatment on associated repairing genes in the kidney of rats with renal ischemia-reperfusion injury / 中华肾脏病杂志

Objective To investigate the effects of intermedin (IMD) pretreatment on associated repairing genes of the rats with injured kidneys by ischemia reperfusion injury (IRI)during the repair and regeneration process.Methods A total of 144 healthy male Wistar rats were randomly divided into 4 gourps:sham opration group,IRI group,empty plasmid group (EP)and IMD group.After resection of right kidneys of the rats,plasmid was transfected into the left kidneys by using ultrasonic microbubble technology.After one week,the renal IRI models were programmed.The samples of renal tissues after 1 d,2 d,3 d,4 d,7 d and 14 d of reperfusion were harvested respectively,then the mRNA expressions of the Pax-2,ZO-1,Ncam,Wt-1 and vimentin in renal tissues were detected by RT-PCR; the protein expressions of Pax-2,Wt-1 and vimentin were analyzed by Western blotting and the protein expressions of ZO-1 and Ncam were measured by ELISIA.Results (1) Compared with the sham group,the mRNA and protein expression of Pax-2,ZO-1,Ncam,Wt-1 and vimentin of the rats in IRI group increased significantly from day 1 to day 3 (P＜0.05),which peaked at day 2.After day 4,the above expressions in IRI group returned to normal level.(2) In IMD group,the mRNA and protein expressions of Pax-2,Zo-1,Ncam,Wt-1 and vimentin were significantly higher than those in other 3 groups (P＜0.05) at the same time after IRI day 1 to day 4,with a maximum in day 2.(3) The above expressions in IRI group,EP group,IMD group had no significant differences compared with sham group after day 7 or day 14 respectively (P＞0.05),and either between IRI group and EP group,though the expressions of the genes in IRI group and EP group increased compared with sham group after day 4.(4) The above expressions between IRI group and EP group also had no significant difference (P＞0.05).(5) Changes of ZO-1 and Ncam protein expression detected by ELISA were similar to those abore mRNA and protein expression by RT-PCR and Western blotting.Conclusion IMD pretreatment plays an important role in up-regulation of the expressions of associated repair genes during the process of repair and regeneration after renal ischemia reperfusion injury.

Effect and mechanism of adrenomedullin on apoptosis of renal tubular epithelial cell in rats induced by renal ischemia reperfusion injury / 中华泌尿外科杂志

Objective To investigate the effect and mechanism of adrenomedullin (AM) on apoptosis of renal tubular epithelial cell in rats induced by renal ischemia reperfusion injury. Methods Thirty-two Wistar rats were randomly divided into 4 groups: control group, IRI group, empty plasmid group and AM group. One week after removing the right kidney, eukaryotic expression vector encoding rat AM gene was transfected into the left kidney using an ultrasound-microbubble mediated system. After 1 week the transfer efficiency was detected by immunohistochemical method . Renal IRI model induced by clamping left renal arteries for 45 min followed by reperfusion for 24 h. Tubular cell apoptosis was detected by TUNEL assay. Bcl-2, Bax and Fas expressions were examined by RT-PCR. The expressions of caspase-3, caspase-8 and caspase-9 were determined by Western bolt analysis. Results The expression of AM in the AM group was significantly higher than the empty plasmid group (0.51±0.09 vs 0.23±0.05; P0.05). Conclusion AM can reduce apoptosis of renal tubular epithelial cell induced by renal IRI, the mechanism of which might be achieved by inhibiting caspase-dependent intrinsic and extrinsic pathways.