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Objective:To analyze and explore the independent risk factors of 28-day mortality in patients with septic myocardial injury.Methods:A retrospective cohort study was conducted to collect clinical data of 505 patients diagnosed with sepsis related myocardial injury admitted to the intensive care unit (ICU) of the Affiliated Hospital of Jining Medical University from January 2015 to December 2020. According to the 28-day survival status of patients, they were divided into survival group and death group. COX multivariate regression analysis was used to analyze the influencing factors of the 28-day mortality rate of sepsis related myocardial injury patients, and receiver operating characteristic (ROC) curves were drawn to evaluate the effectiveness of independent risk factors in predicting the 28-day mortality rate of sepsis related myocardial injury patients.Results:A total of 505 patients with sepsis myocardial injury were included, of which 282 survived on 28 days and 223 died, with a mortality rate of 44.16%. COX multivariate regression analysis showed that Sequential Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score, blood lactate (LAC), oxygenation index (PaO 2/FiO 2), admission heart rate, and albumin were independent risk factors for sepsis associated myocardial injury mortality at 28 days (all P<0.05). ROC curve analysis showed that the area under the ROC curve (AUC) of SOFA score was 0.766 2, and the 95% confidence interval (95% CI) was 0.724 5-0.807 9; The predictive value of 28-day mortality in sepsis associated myocardial injury patients was superior to APACHE Ⅱ score, LAC, PaO 2/FiO 2, admission heart rate, and albumin [The AUC values were 0.754 1(0.711 5-0.796 7), 0.752 6(0.710 1-0.795 1), 0.697 0(0.649 7-0.744 2), 0.623 2(0.573 7-0.672 7), and 0.620 3(0.570 8-0.669 7), respectively]. Conclusions:SOFA score, APACHE Ⅱ score, LAC, PaO 2/FiO 2, admission heart rate, and albumin are independent risk factors for the 28-day mortality rate of sepsis related myocardial injury. Clinical practice should identify these factors early, intervene early, and improve patient prognosis.
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Objective:To investigate the changes of quadriceps femoris thickness with the length of stay in intensive care unit (ICU) in patients with sepsis, and to evaluate the diagnostic value of muscle changes in mortality.Methods:A prospective study was conducted, and 92 patients with sepsis who were admitted to the ICU of the Affiliated Hospital of Jining Medical College from January 2020 to December 2021 were enrolled. The thickness of quadriceps femoris [including the quadriceps femoris muscle thickness at the midpoint of the anterior superior iliac spine and the upper edge of the patella (M-QMLT), and at the middle and lower 1/3 of the patella (T-QMLT)] measured by ultrasound 1 day (D1), 3 days (D3), and 7 days (D7) after admission to the ICU were collected. The atrophy rate of quadriceps femoris was calculated 3 and 7 days after admission to the ICU compared with 1 day [(D3-D1)/D1 and (D7-D1)/D1, (TD3-TD1)/TD1 and (TD7-TD1)/TD1, respectively]. The demographic information, underlying diseases, vital signs when admission to the ICU and in-hospital mortality of all patients were recorded, and the differences of the above indicators between the two groupswere compared. Multivariate Logistic regression was used to analyze the influence of quadriceps femoris muscle thickness and atrophy rate on in-hospital mortality of septic patients. The receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of quadriceps femoris muscle thickness and atrophy rate on in-hospital mortality of septic patients.Results:A total of 92 patients with severe sepsis were included, of which 41 patients died in hospital, 51 patients discharged. The in-hospital mortality was 44.6%. The muscle thickness of quadriceps femoris in severe septic patients decreased with the prolongation of ICU stay, and there was no significant difference between the two groups at the first and third day of ICU admission. The muscle thickness of quadriceps femoris at different measuring positions in the survival group was significantly greater than those in the death group 7 days after admission to the ICU [M-QMLT D7 (cm): 0.50±0.26 vs. 0.39±0.19, T-QMLT D7 (cm): 0.58±0.29 vs. 0.45±0.21, both P < 0.05]. The atrophy rate of quadriceps femoris muscle thickness at different measuring positions 3 and 7 days after admission to ICU in the survival group was significantly lower than those in the death group [(D3-D1)/D1: (8.33±3.44)% vs. (9.74±3.91)%, (D7-D1)/D1: (12.21±4.76)% vs. (19.80±6.15)%, (TD3-TD1)/TD1: (7.83±4.26)% vs. (10.51±4.75)%, (TD7-TD1)/TD1: (11.10±5.46)% vs. (20.22±6.05)%, all P < 0.05]. Multivariate Logistic regression analysis showed that M-QMLT D7, T-QMLT D7, (D3-D1)/D1, (D7-D1)/D1, (TD3-TD1)/TD1, (TD7-TD1)/TD1 were independent risk factors for in-hospital mortality (all P < 0.05). The results were stable after adjusting for confounding factors. ROC curve analysis showed that (TD7-TD1)/TD1 [area under the ROC curve (AUC) was 0.853, 95% confidence interval (95% CI) was 0.773-0.934] was superior to (D7-D1)/D1, T-QMLT D7, M-QMLT D7, (TD3-TD1)/TD1 and (D3-D1)/D1 [AUC was 0.821 (0.725-0.917), 0.692 (0.582-0.802), 0.683 (0.573-0.794), 0.680 (0.569-0.791), 0.622 (0.502-0.742)]. Conclusions:For septic patients in ICU, bedside ultrasound monitoring of quadriceps femoris muscle thickness and atrophy rate has a certain predictive value for in-hospital mortality, and a certain guiding significance in clinical treatment and predicting the prognosis of sepsis.
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Objective:To investigate the relationship between the arterial blood lactic acid level after entering the intensive care unit (ICU) and the 28-day mortality of patients with septic shock.Methods:The clinical data of 303 patients with septic shock hospitalized in the department of critical medicine of the Affiliated Hospital of Jining Medical College from April 2015 to June 2019 were analyzed retrospectively. According to the blood lactate (Lac) level, the patients were divided into <4 mmol/L group ( n=203), 4-10 mmol/L group ( n=69) and >10 mmol/L group ( n=31). The baseline characteristics of the patients were analyzed. Multiple logistic regression analysis was used to analyze the independent influencing factors of the 28-day mortality of patients with septic shock. The receiver operating characteristic (ROC) curve was used to analyze the predictive value of the Lac level after entering the ICU for 28-day mortality, and Kaplan-Meier survival curve was performed according to the best cut-off value. Results:A total of 303 patients with septic shock were included, with 179 died in 28 days, and the total mortality was 59.08%. There were 203, 69, 31 patients in Lac<4 mmol/L, 4-10 mmol/L and >10 mmol/L group, respectively. There were significant differences in Acute Physiology and Chronic Health Evalution Ⅱ (APACHE Ⅱ), Sequential Organ Failure Assessment (SOFA), oxygenation index (PaO 2/FiO 2), abdominal infection, the proportion of vasoactive drugs use among the three groups ( P<0.05). Multiple logistic regression analysis showed that the independent influencing factor of the 28-day mortality of septic shock were age, SOFA, use of mechanical ventilation, lactic acid (Lac). ROC curve analysis showed that the area under the ROC curve (AUC) for predicting 28-day mortality of patients with septic shock was 0.604 5 (95% CI: 0.540 8-0.668 2). When the optimal cut-off value was 3.55 mmol/L, the sensitivity was 0.508 4, the specificity was 0.733 9, the positive likelihood ratio was 1.910 3 and the negative likelihood ratio was 0.669 9. According to the best cut-off value of entrance Lac, patients were divided into high Lac group (≥3.55 mmol/L) and low Lac group (<3.55 mmol/L), and their 28-day mortality rates were 73.39%(91/124) and 49.16%(88/179). Kaplan-Meier survival curve showed that the 28-day cumulative survival rate of the high Lac group was significantly lower than that of the low Lac group ( P<0.001). Multiple logistic regression analysis showed that after adjusting for confounding factors, the 28 d mortality increased to 1.22 times for each increase of 1 mmol/L of Lac [odds ratio ( OR)=1.22, 95% confidence interval (95% CI) was 1.08-1.37, P=0.001 4]. The 28 d mortality in high Lac group was 3.53 times higher than that in low Lac group ( OR=3.53, 95% CI was 1.36-7.09, P=0.000 4). Conclusions:In patients with ICU septic shock, the arterial blood Lac level after admission was associated with 28-day mortality. Patients with septic shock whose arterial blood Lac level exceeded 3.55 mmol/L within 1 hour of entering the room had a significantly increased risk of death.
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Objective: To investigate the application of single-molecule PCR (SM-PCR) in the detection of plasma ctDNA for the treat-ment of patients with advanced lung adenocarcinoma. Methods: In total, 30 patients diagnosed with advanced lung adenocarcinoma were enrolled between June 2017 and May 2018. ctDNA fragments of the target genes (EGFR, KRAS, BRAF, ALK, HER2, and TP53) from the blood samples were enriched by SM-PCR, and DNA libraries were prepared. Finally, a high-throughput sequencing was performed. The EGFR detection of tumor tissue samples was performed using real-time fluorescence PCR based on the amplification refractory mutation system (ARMS) and consistency in the results of EGFR mutation detection in the plasma and tissue was compared. Results:The results of both the methods were consistent (Kappa=0.867, P<0.001). The McNemar's test also indicated that the results are not statistically different (P=0.500). Conclusions: SM-PCR can be used for the detection of plasma EGFR mutations. The target detection sites are more comprehensive and multiple mutations can be detected at the same time. Results of the analysis are more precise and can be absolutely quantified.
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OBJECTIVE To develop a new method for detecting 22q11.2 deletion syndrome (22q11.2 DS) in clinical settings. METHODS Specific primers and fluorescence probes were designed to target the TBX1 gene within the 22q11.2 deletion region and a reference gene RPP30. Multiplexed droplet digital PCR (ddPCR) was run to detect the 22q11.2 microdeletion by calculating the ratio of positive droplet number of TBX1/RPP30. RESULTS Three cases of 22q11.2 microdeletion previously confirmed by array comparative genome hybridization were successfully identified. Subsequently, the ddPCR detected two further cases of 22q11.2 microdeletion among 14 children with congenital heart diseases. CONCLUSION The ddPCR technique has provided a rapid and cost-effective method for detecting 22q11.2 microdeletion in clinical settings.
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Objective To study the impact of earthquake disasters on the mental health of military medical personnel during emergency rescue. Methods Three hundred military medical personnel who participated in the emergency rescue of earthquake disasters in five military hospitals in Shaanxi Province were selected as the study subjects, and their mental health levels were analyzed using the Mental Symptom Checklist 90 (SCL-90). Results In this survey, a total of 300 SCL-90 questionnaires were issued, 300 were recovered, and the effective recovery rate was 100%. Only 30.67%(92/300) of people participated in emergency disaster rescue during investigation, 31.33% (94/300) had psychological problemsafter arriving in the earthquake-stricken area after one week, such as somatization, obsessive-compulsive disorder, anxiety, and horror. SCL-90 scores were 0.45±0.03, 1.13±0.13, 0.79 ±0.08, 1.07±0.09, 1.01±0.14. The psychological stress response rates of the emergency response of military medical staff of different characteristics were different. Among them, the stress response rates of military personnel with different degrees (specialty, bachelor or above) and whether they have participated in rescue work were 74.07% (40/54), 21.95% (54/246), 15.22% (14/92), 38.46% (80/208).The difference was statistically significant (χ2=55.913,16.018, P<0.01). Conclusions The medical staff of the army participating in the earthquake disaster rescue has psychological pressure due to many injuries, environmental risks, lack of supplies, etc. The medical unit should provide adequate training in theory and practice to its personnel and focus on the mental health of rescue workers, give timely psychological counseling to ensure the successful completion of the rescue.
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OBJECTIVE:To control the risk of off-label drug use,and to provide reference for rational drug use. METHODS:Outpatient prescriptions were selected by stratified equal proportion sampling method from a third grade class A hospital during Jun. 2015-Jun. 2016. According to the latest edition of drug instruction issued by CFDA,the off-label prescriptions were screened and analyzed statistically. According to Micromedex tools and literatures report,guidelines,off-label drug use and related severe ADR were analyzed. RESULTS:Of 3 025 outpatient prescriptions,11.2% of prescriptions(339 pieces)were considered as off-label prescriptions,including without indication(88.7%),over dose(6.0%),beyond route of administration(3.2%)and beyond adapt-to-the-crowd(2.1%). Gastroesophagedal reflux was the main diagosis(16.0%). 1.5% of off-label drug use were supported by FDA-approved labels,83.8% of them were supported by international and national guidelines,12.4% of them were supported by expert consensus,and 2.4% of them were supported by other literature report. Thirteen items of off-label drug use had been included in Micromedex,recommendation grade and evidence intensity of which varied. Eight drugs of off-label drug use were reported to result in serious ADR. CONCLUSIONS:All off-label drug use in outpatient department of this hospital is supported by evidence-based medical evidence. But the quality of evidence varies. In the practice,physicians and pharmacists should balance the benefit and risk of off-labed drug use carefully.
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Objective@#To investigate the factors that impacts of therapeutic effect in advanced non-small cell lung cancer (NSCLC) patients with mild tumor enlargement and the rational therapeutic strategy for them.@*Methods@#The clinicopathological features and prognostic data of advanced NSCLC patients whose sum of tumor longest diameters with 0 to 20% increase were retrospectively explored, and the Cox proportional hazards model was used to analyze the independent prognostic factors in patients.@*Results@#The median progression-free survival (PFS) of 54 patients with the original regimen was 87 days, significantly less than 168 days of the median PFS of 49 patients with replacing regimen (P<0.001). The median PFS of other chemotherapeutic regiems (154 days) and the targeted therapy (287 days) were longer than the origional therapy (P<0.05 for all). The left 7 patients received radiotherapy. Receiver operating characteristic (ROC) curve indicated a significant difference in the PFS when the maximal cut-off value of tumor enlargement ratio was 7%. Univariate analysis of patients with targeted therapy after disease progression showed that gender, pathological type, clinical stage, lung metastasis and tumor enlargement ratio were the prognostic factors (all of P<0.05). Multivariate analysis showed that the tumor enlargement ratio was an independent prognostic factor (P=0.001). Single factor analysis showed that the chemotherapeutic regimens before and after disease progression were prognostic factors of patients received chemotherapy after disease progression (P<0.05). Cox multivariate analysis showed that the chemotherapeutic regimen after disease progression was an independent prognostic factor of patients (P=0.004). In the patients whose tumor enlargement ratio was 0 to 7%, Univariate analysis showed that chemotherapeutic regimen before tumor enlargement was a prognostic factor (P=0.030), while Cox multivariate analysis showed that it was not an independent prognostic factor (P=0.560). In the patients whose tumor enlargement ratio was 7.1% to 20%, single factor analysis showed that pathological type, bone metastasis and chemotherapeutic regimen after disease progression were prognostic factors (all of P<0.05), and Cox multivariate analysis showed that all of them were independent prognostic factors of these patients (all of P<0.05).@*Conclusions@#To the advanced NSCLC patients whose tumor enlargement ratio is 0 to 20%, the PFS of patients receive replacing regimen is longer than that of patients receive original regimen. There is a significant difference in the PFS when the maximal cut-off value of tumor enlargement ratio is 7%. To patients undergo second-line chemotherapy before disease progression and the tumor enlargement ratio is 7.1% to 20%, the PFS of patients receive replacing regimen is significantly extended. Dual drug replacing regimen is especially benefit to the adenocarcinoma patients without bone metastasis.
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Objective To explore the value of echocardiography in evaluation of pulmonary venous in total anomalous pulmonary venous connection (TAPVC).Methods Fifty-five children with TAPVC were enrolled in the study.The data of echocardiography and CT angiography were retrospectively analyzed and compared with intraoperative findings.Results Totally 55 patients with TAPVC were classified into supra-cardiac type (n=24),cardiac type (n=20),infra-cardiac type (n=7) and mixed type (n=4) according to the sites of drainage of pulmonary venous in echocardiography.In 15 patients with obstruction of pulmonary vertical vein,the sites of obstruction in the supra-cardiac type mostly presented between vertical vein and superior vena cava or innominate vein,and the sites of obstruction in the infra-cardiac presented all between vertical vein and hepatic or portal vein.In 4 patients with pulmonary vein stenosis,3 cases with local pulmonary vein stenosis were all cardiac type,which presented between individual pulmonary vein and common confluence or right atrium;1 patient with diffuse pulmonary vein stenosis was infra-cardiac type.In 9 patients of abnormal individual pulmonary vein,8 cases were not detected by echocardiography,but all were detected by CT angiography.Conclusion Echocardiography is able to make more comprehensive evaluation for the pulmonary venous drainage,obstruction,and proximal stenosis of individual pulmonary vein in TAPVC.CT angiography is superior in evaluation of abnormalities of connection and amount of individual pulmonary vein,and imaging of distal pulmonary vein.
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OBJECTIVE:To control the risk of off-label drug use,and to provide reference for rational drug use. METHODS:Outpatient prescriptions were selected by stratified equal proportion sampling method from a third grade class A hospital during Jun. 2015-Jun. 2016. According to the latest edition of drug instruction issued by CFDA,the off-label prescriptions were screened and analyzed statistically. According to Micromedex tools and literatures report,guidelines,off-label drug use and related severe ADR were analyzed. RESULTS:Of 3 025 outpatient prescriptions,11.2% of prescriptions(339 pieces)were considered as off-label prescriptions,including without indication(88.7%),over dose(6.0%),beyond route of administration(3.2%)and beyond adapt-to-the-crowd(2.1%). Gastroesophagedal reflux was the main diagosis(16.0%). 1.5% of off-label drug use were supported by FDA-approved labels,83.8% of them were supported by international and national guidelines,12.4% of them were supported by expert consensus,and 2.4% of them were supported by other literature report. Thirteen items of off-label drug use had been included in Micromedex,recommendation grade and evidence intensity of which varied. Eight drugs of off-label drug use were reported to result in serious ADR. CONCLUSIONS:All off-label drug use in outpatient department of this hospital is supported by evidence-based medical evidence. But the quality of evidence varies. In the practice,physicians and pharmacists should balance the benefit and risk of off-labed drug use carefully.
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Objective To explore the influencing factors on short -term efficacy of intravenous thrombolysis with rt -PA.Methods The clinical data of the 95 acute ischemic stroke(AIS)patients who received thrombolytic therapy were analyze.Multivariate logistic regression analysis was used to determine the possible influencing factors. Results Fifty -six(58.95%)patients had favourable outcomes after thrombolytic therapy for 24 hours.Multivariate logistic regression analysis indicated that diabetes(OR =3.933,95% CI 1.199 ~12.897)and TOAST classification (OR =1.448,95% CI 1.032 ~2.032 )were the independent predictors of short -term outcome.Conclusion Diabetes and TOAST classification are the major influencing factors of short -term efficacy after intravenous thrombolysis with rt -PA.It should pay attention screening patients for intravenous thrombolysis therapy and predicting the efficacy of thrombolysis.
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AIM:To investigate the regulation mechanism for insufficient KChIP 2 expression induces Ito,f downregulation and arrhythmogene-sis in cardiac hypertrophy .METHODS:Bidirectional manipulations of MG 53 expression were performed by adenoviral overexpression of MG53 or knockdown of MG53 with RNA interference in neonatal rat ventricular myocytes with or without PE stimulation .Ito,f was re-corded with patch clamp in whole-cell mode 48 h after adenoviral transfection .Then the WT or MG53 knockout ( MG53 -/-) mouse model of left ventricular hypertrophy induced by transverse aortic constriction ( TAC) were used to detect the susceptibility to ventricu-lar arrhythmia.RESULTS: Here, we show muscle-specific MG53 regulates KChIP2 expression and Ito,f densities, where they are downregulated in hearts from MG53 knockout mice and MG53 knockdown rat cardiomyocytes , but upregulated in MG53 overexpressed cells.MG53 expression is decreased in phenylephrine ( PE)-induced cardiomyocyte hypertrophy and restoration of MG 53 rescues PE-induced downregulation of KChIP2 and Ito,f.Furthermore, MG53 is decreased in a mouse model of hypertrophy induced by transverse aortic constriction and ablation of MG 53 increases the susceptibility to ventricular arrhythmia by exaggerating Ito,f remodeling.CON-CLUSION:These findings establish MG53 as a novel regulator of Ito,f and its central role in arrhythmogenesis in hypertrophy .
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Objective To explore the relationship between osteoporosis knowledge and activities and fear of falling of elderly in the community.Method 420 elders in community were investigated with osteoporosis knowledge assessment tool (OKAT) and the modified survey of activities and fear of falling in the elderly (MSAFFE).Result The overall average score of MSAFFE was (25.36±4.58),and exercise capacity dimension scored higher (13.89±2.41).The overall average score of OKAT was (9.11±3.81).The correlation coefficient of MSAFFE and OKAT was-0.11～ 0.58(P＜0.05).The level of knowledge osteoporosis could explain 24％,18％,16％ variation of activities and fear of falling in each dimension.Conclusion The level of knowledge osteoporosis in the elderly is closely related to activity and fear of falling.Health education should be strengthened to improve the life quality of older people.
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Objective: This study aimed to examine the number of activated circulating endothelial cells (aCECs) in the peripheral blood of patients with non-small cell lung cancer (NSCLC), and investigate the relationship among aCECs, anti-angiogenic therapy, and prognosis of NSCLC patients. This study also aimed to identify novel predictive markers for anti-angiogenic therapy, and provide basic data and experimental basis for establishing an evaluation system for this therapy. Methods: A total of 142 NSCLC patients were randomly divided into the chemotherapy group (Group 1) and combined therapy group (i.e., chemotherapy plus endostatin, Group 2). The number of aCECs was measured using flow cytometry by detecting the expression status of CD105 and CD146 in the peripheral blood. The correlation between the changes in aCECs and efficacy of drug treatment was statistically analyzed using SPSS software. Results:The number of aCECs in Group 2 increased significantly at 8 and 29 d, two cycles, 50 and 71 d, and four cycles after treatment, respectively (P<0.05). In particular, aCECs amount in cases of progressive disease increased more significantly after combined therapy (P<0.05). A negative correlation was found between the treatment cycle and difference in aCECs amount before and after therapy (r=-0.970, P=0.001). A negative correlation was also observed between the difference in aCECs amount and time to tumor progression (TTP) (r=-0.351, P=0.039). Therefore, the difference in aCECs amount before and after therapy could serve as an important predictor for TTP in NSCLC patients. Conclusion:CD105 and CD146 reflected the activation status of endothelial cells, and responded to the drug treatment. Thus, CD105 and CD146 could act as ideal markers for aCECs. The number of aCECs increased during cancer progression, but significantly decreased after long-term treatment. Therefore, the change in aCECs amount may be a useful marker in predicting the efficacy of anti-angiogenic therapy.
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Objective: This work aimed to investigate the negative prognostic factors of bronchioloalveolar carcinoma (BAC) and adenocarcinoma with BAC characteristics, based on the 2004 pathological classification by the World Health Organization (WHO), which were further verified with the new pathological classification of lung adenocarcinoma (WHO 2011), to identify crucial factors that determine the prognosis of BAC and adenocarcinoma with BAC features, and to prove the coherence of the two pathological classi-fications in assessing clinical prognosis. Methods: Upon pathological diagnosis, some of the 193 cases of BAC or adenocarcinoma with BAC features were categorized into adenocarcinoma in situ (AIS) or minimally invasive adenocarcinoma (MIA), based on the 2011 WHO classification. Gender, age, tumor size, familial cancer history, smoking history, TNM stage, symptoms, duration of symp-toms, and the choice of treatment were recorded and analyzed for prognosis. The survival rate was calculated by Kaplan-Meier method. Log-rank test was introduced to compare the survival rate. Univariate and multivariate factors for the survival rate were analyzed by Cox proportional hazards regression model. Results:The overall 1-, 3-and 5-year survival rates were 84.3%, 60.6%, and 45.6%, respec-tively. Cox univariate analysis revealed that the tumor size, symptoms, TNM stage, pathological outcomes, and the choice of treatment were all prognostic factors. Cox multivariate analysis revealed that TNM stage was an independent prognostic factor for patients with BAC. Data from patients with AIS and MIA revealed better survival. Conclusion:The overall survival rate of BAC and adenocarcino-ma with BAC features are superior to that of other non-small cell lung cancer (NSCLC). The clinical symptoms are non-specific com-pared with other types of NSCLC. Clinical stage at diagnosis is a key prognostic factor, such that early correct diagnosis significantly improves survival. The new classification criteria of WHO, released in 2011, is more elaborate and more conducive to clinical practice.
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Objective To explore whether hypoxia-inducible factor-1α( HIF-1α )is involved in oxygenglucose deprivation (OGD)induced caspase-independent cell death in primary cortical neurons and whether their expression is infected by necrostatin-1 ( Nec-1 ).Methods ( 1 ) Primary cerebrocortical neurons were cultured for 14 days.Pretred z-VAD.Fmk (z-VAD)and Nec-1 with 0.1,1,5,10,25 and 50 μ mol/L before the neurons were exposed to OGD for 2 hours and reoxygenated for 12 hours,then cell viability was determined by measure LDH level.(2)Pretred z-VAD before the neurons were exposed to OGD for 2 hours,then reoxygenated for 0,2,6,12,24and 48 hours.Then western blot analysis protein level of HIF-1 α ;rt-PCR check its RNA level.(3)Pretred z-VAD and Nec-1 with 25μ mol/L before the neurons were exposed to OGD for 2 hours and reoxygenated for 12 hours.Then western blot analysis protein level of HIF-1 α; rt-PCR check its RNA level.Result ( 1 ) When cells were pretread Nec-1 with 5 μ mol/L(6.97 ± 0.06),the level of LDH was lower than cells untreated( 14.23 ± 0.08 ) (P＜ 0.05);At 25 μmol/L( 2.21 ± 0.05),the level of LDH was essentially the same as that of the control( 1.03 ±0.03 ) (P＞0.05).(2)The protein level of HIF-1 αwas different from normal (0.24 ±0.01 ) when exposed to OGD for 2 hours and reoxygenated for 2 hours (0.57 ± 0.09) and was highest after cells were exposed to OGD for 2 hours and reoxygenated for 12 hours(0.91 ± 0.08 ) (P＜ 0.05 ).The RNA level of HIF-1 α when cells were exposed to OGD was not deferent from normal (P ＞ 0.05 ).( 3 ) When cells were pretread with Nec-1 (0.32 ± 0.04 ),the protein level of HIF-1α were lower than untreated(0.83 ±0.03) (P＜0.05),but the RNA level of HIF-1α had no deference(P ＞ 0.05).Conclusion HIF-1α was involved in cell' s caspase-independent cell death;Nec-1 can protect neurons through inhibiting the expression of HIF-1α.
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Objective To investigate the location of receptor interacting protein 3( RIP3) in Necroptosis and its function in this signal passage, and explore the relationship between receptor interacting protein 1 ( RIP1 ) and RIP3 in nuclear translocation. Methods Primary cerebrocortical neurons were cultured for 12 days,then pre-treated with zVAD-fmk(20μ,mol/L) for half an hour to block apoptosis. ①Extracting nuclear and cytoplasmic protein after neurons were exposed to TNF for different time ,then protein levels of RIP3 were analyzed by western blot and immunofluorescence for qualitative observation;②In the following research,the neurons were treated with Nec-1 and shRlPl ,then the protein level of RIP1 and RIP3 with western blot were analyzed, cell viability were determined by measuring LDH levels. Results ①In signaling pathways of necroptosis, the protein level of RIP3 in cytoplasmic decreased gradually with prolonged TNF exposure, to the corresponding it rolled up in nucleus and a-chieved the peak in 12 hours of TNF treatment ( Cytoplasmic 0. 45 ± 0. 03 ,0. 41 ± 0. 02,0. 73 ± 0. 03 ,0. 90 ± 0.01,1.15 ±0.04,1.30 ±0.02,0.99 ±0.03,0.63 ±0. 03;Nucleus 0. 07 ±0.02,0. 26 ±0.02,0. 57 ±0. 02,0. 68 ± 0.02,0. 80 ± 0.01,0.92 ± 0.02,1.28 ± 0.03,0. 87 ± 0.02) (P < 0.01). ②Blocking the relationship between RIP1 and RIP3 with necrostatin-1 and shRIPl , nuclear translocation of RIP3 decreased and caused a great increase in cell viability( 1.00 ±0.05,0.39 ±0.03,0.50 ±0. 03) (P<0. 01). Conclusion RIP3 mainly locates in cy-tolymph of normal cells,it translocates into nucelus as necroptosis takes place. RIP1 function with RIP3 in nuclear translocation. Block nuclear translocation of RIP3 is a potential way to protect cells.
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Objective To explore the role of hypoxia inducible factor 1α(HIF-1α)-mediated signaling pathway in angiotensin Ⅱ(Ang Ⅱ)induced renal interstitial fibrosis. Methods Renal tubular epithelial cells were cultured and treated with different concentrations (10-9-10-6 mol/L)of Ang Ⅱ for 24 h and 48 h.Real-time quantitative PCR and Western blotting were preformed to detect the mRNA and protein expressions of HIF-1α,prolyl hydroxylase 2 (PHD2)and tissue inhibitor of metalloproteinase 1 (TIMP-1)in renal tubular epithelial cells. Results HIF-1αmRNA level was increased with Ang Ⅱ treatment in a concentration dependent manner.When cells were treated with Ang Ⅱ concentration at 10-7mol/L for 24 h,the mRNA level was markedly increased by 166%.Furthermore,by real-time quantitative PCR and Western blotting,compared with the control group,Ang Ⅱincreased the mRNA and protein levels of HIF-1α and TIMP-1 (P<0.05,respectively),while the mRNA and protein levels of PHD2 were decreased markedly (P<0.05,respectively)in renal tubular epithelial cells.Conclusion Ang Ⅱ reduces HIF-1αdegradation in renal tubular epithelial cells probably by reducing the expression of PHD2,which increases the expressions of HIF-1α and TIMP-1 involved in renal interstitial fibrosis.