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ObjectiveTo explore the therapeutic effect and mechanism of Guipitang on rats with myocardial ischemia. MethodFifty SD rats were divided into five groups： a control group， a model group， low and high-dose Guipitang （7.52， 15.04 g·kg-1） groups， and a trimetazidine group （0.002 g·kg-1）. By intragastric administration of vitamin D3 and feeding rats with high-fat forage and injecting isoproterenol， the rat model of myocardial ischemia was established. After drug treatment of 15 d， an electrocardiogram （ECG） was performed to analyze the degree of myocardial injury. A fully automatic biochemical analyzer was used to detect the changes in the serum levels of total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C）. Hematoxylin-eosin （HE） staining and Masson staining were used to observe myocardial histopathological changes. TdT-mediated dUTP nick end labeling （TUNEL） staining was used to detect cardiomyocyte apoptosis. Western blot was adopted to detect the protein levels of extracellular signal-regulated kinase 1/2 （ERK1/2）， phospho-ERK1/2 （p-ERK1/2）， p38 mitogen-activated protein kinase （p38 MAPK）， phospho-p38 MAPK （p-p38 MAPK）， B-cell lymphoma-2 （Bcl-2）-associated X （Bax）， Bcl-2， and cleaved cysteine aspartate proteolytic enzyme （cleaved Caspase-3）. ResultCompared with the control group， the ECG S-T segment decreased in the model group. The serum levels of TC， TG， and LDL-C were increased significantly （P<0.05）. The arrangement of myocardial tissue was disordered， and the proportion of cardiomyocyte apoptosis increased. The protein levels of cleaved Caspase-3， Bax， and p-p38 MAPK in the heart were increased， and the Bcl-2 expression was decreased （P<0.05）. Compared with the model group， the S-T segment downward shift was restored in the low and high-dose Guipitang groups and trimetazidine group， and the levels of TC， TG， and LDL-C were decreased. The protein expression of cleaved Caspase-3 and Bax in the heart dropped， and p-p38 MAPK and p-ERK1/2 protein expressions increased significantly （P<0.05）. The degree of myocardial injury was alleviated， and the proportion of cardiomyocyte apoptosis decreased. Bcl-2 protein expression was increased significantly in the low-dose Guipitang group （P<0.05）. ERK1/2 and p38 MAPK proteins had no significant difference among different groups. ConclusionGuipitang could alleviate myocardial injury and inhibit cardiomyocyte apoptosis in rats by activating the expression of ERK1/2 and p38 MAPK.
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Objective:To compare the predictive value of parameters extracted from circular region-of-interest (ROI) with whole-liver histogram on gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced T 1 map for postoperative liver failure in patients with liver focal lesions. Methods:The data of patients who underwent Gd-EOB-DTPA-enhanced MRI for focal liver lesions in Zhongshan Hospital, Fudan University from March 2016 to March 2018 were analyzed retrospectively. Forty patients were enrolled, including 30 males and 10 females, aged (56.6±12.1) years. According to the occurrence of postoperative liver failure, forty patients were divided into liver failure group ( n=14) and control group ( n=26). The parameters extracted from circular ROIs and whole liver histogram on T 1 map before Gd-EOB-DTPA enhancement and in hepatobiliary phase (HBP) were compared between the two groups. The receiver operating characteristic (ROC) curve was used to evaluate the value of these parameters in predicting postoperative liver failure. Results:The mean, standard deviation, median and 95% quantile of T 1 HBP in histogram parameters of liver failure group were significantly higher than those of control group (all P<0.05). The three parameters extracted from circular ROIs were not effective in predicting liver failure after hepatectomy (all P>0.05). Among all the liver histogram parameters, the area under the ROC curve of the 95% quantile before T 1 enhancement for predicting postoperative liver failure was 0.702 (95% CI: 0.523-0.881), the standard deviation of T 1 HBP was 0.739 (95% CI: 0.568-0.910), and the 95% quantile of T 1 HBP was 0.721 (95% CI: 0.540-0.903). The predictive efficacy were good (all P<0.05). Among them, the predictive performance of T 1 HBP standard deviation was the best, the area under the ROC curve was 0.739, the sensitivity was 85.7%, the specificity was 57.7%, and the best threshold was 54.8 ms. Conclusions:When Gd-EOB-DTPA enhanced T 1 mapping is used to predict postoperative liver failure in patients with focal liver lesions, the whole-liver histogram analysis is superior to the conventional circular ROI-based statistical method.
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Objective:To study the impacts of pre-pregnancy body mass index (BMI), gestational diabetes mellitus (GDM) and gestational weight gain (GWG) on perinatal outcomes and mode of delivery.Methods:From November 2016 to December 2017, single-pregnancy women in early pregnancy (<13 weeks) regularly checked-up at our hospital were enrolled in this prospective cohort study and followed up until delivery. They were assigned into four groups according to pre-pregnancy BMI: obese group (≥28.0 kg/m 2), overweight group(24.0-<28.0 kg/m 2), normal group (18.5-<24.0 kg/m 2) and underweight group(<18.5 kg/m 2). A 75-g oral glucose tolerance test was performed at 24-28 weeks of pregnancy to screen for GDM. The optimal GWG was 11.0-16.0 kg for underweight group, 8.0-14.0 kg for normal group, 7.0-11.0 kg for overweight group and 5.0-9.0 kg for obesity group. The effects of pre-pregnancy BMI, GDM and GWG on perinatal outcomes and delivery mode were evaluated using multivariate logistic regression methods. Results:A total of 802 pregnant women were included. The incidences of pre-pregnancy overweight and obesity were 21.8% and 8.9%, respectively. The incidence of GDM was 14.1%. 57.2% of the participants experienced excessive GWG. The incidences of macrosomia, low birth weight and premature birth were 7.1%, 2.7% and 2.2%, respectively. The incidence of Cesarean delivery (C-section) was 37.7%. Pre-pregnancy obesity [adjusted odds ratio ( AOR)=4.355, 95% confidence interval ( CI) 1.900-9.980] and excessive GWG ( AOR=3.799, 95% CI 1.796-8.034) were independent risk factors for macrosomia. Excessive GWG was a protective factor for low birth weight ( AOR=0.279, 95% CI 0.084-0.928) and inadequate GWG was a risk factor for low birth weight ( AOR=10.954, 95% CI 3.594-33.382) and premature birth ( AOR=8.796, 95% CI 2.628-29.438). Compared with the normal group, overweight group had an increased risk of C-section ( AOR=1.817, 95% CI 1.119-2.949). Compared with pregnant women without pre-pregnancy overweight/obesity, GDM nor excessive GWG, any combination of two of the above-mentioned three factors increased the risks of macrosomia ( AOR=3.908, 95% CI 1.630-9.370) and C-section ( AOR=2.269, 95% CI 1.325-3.886). The risks of macrosomia and C-section were the highest when all three factors existed. Conclusions:Pre-pregnancy obesity and excessive GWG are independent risk factors for macrosomia and pre-pregnancy overweight is a risk factor of C-section. Exposure to any two of the three factors (pre-pregnancy overweight/obesity, GDM and excessive GWG) increases risks of macrosomia and C-section and the highest risk is observed when all three factors are present.
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Objective:To study the clinical features, diagnosis, treatment and genetic characteristics of neonatal-onset protein C deficiency (PCD).Methods:The clinical data of a newborn patient with severe PCD admitted to our neonatal department was reviewed. Databases including CNKI, Wanfang Database, CMB, VIP database, PubMed, Embase and SCI database were searched using" infantile", " neonate ", "newborn", "protein C deficiency" and "purpura fulminans" as key words. Published cases of PCD were analyzed.Results:The patient was a full-term female infant who developed multiple symptoms within 2 days after birth. The symptoms included thrombocytopenia, intracranial hemorrhage, purpura fulminans (PF), disseminated intravascular coagulation (DIC), celiac hemorrhage, hypertension, portal and iliac vein thrombosis, purulent meningitis and retinal detachment. Protein C activity was less than 10%. Genetic tests showed compound heterozygous mutations c.314G>T (p.c105f) of paternal origin and c.1218G>A (p.m406i) of maternal origin in PROC gene. According to ACMG guidelines, the mutations were strongly suspected pathogenic variants and consistent with an autosomal recessive (AR) inheritance pattern. The patient was discharged after 6 weeks of treatment at parents' request of withdrawal. A total of 25 articles on 29 patients with relatively complete clinical data were retrieved, including 18 males and 11 females. 4 patients were preterm and 25 full-term. 28 patients showed symptoms within 7 days after birth. The common clinical features were cutaneous PF and splanchnic thrombi. 22 cases documented protein C activity and ranged from 0 to 25%. 16 patients had PROC gene abnormalities and compound heterozygous mutations were found in 10 patients. Among the 22 patients with prognostic data, 11 died (9 within 3 months after birth), the remaining survivors suffered from sequelae including severe intellectual motor development disorder, epilepsy and blindness.Conclusions:The main clinical manifestations of neonatal-onset PCD include PF, DIC, multi-organ hemorrhage and thrombus. The disease is acute and severe, with rapid progression, poor prognosis and high fatality rate. Protein C activity and PROC gene testing may help establish the diagnosis.
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Objective:To explore the clinical characteristics of neonate with arrhythmia and the potential risk factors for cardiac insufficiency.Methods:Research data were collected from the cases of neonate with arrhythmia from January 2017 to June 2021 at the Neonatology Department at Children′s Hospital Capital Institute of Pediatrics.A retrospective analysis was conducted to summarize the clinical features and analyze the risk factors of arrhythmia leading to cardiac insufficiency.Results:A total of 90 cases were enrolled, with a male to female ratio of 1.43∶1(53∶37), and the median gestational age was 39(37, 40)weeks; with 16(17.8%) premature infants, 74 full-term infants(82.2%), and the median onset age was 3(0, 11)days.In this group, 63.3% cases(57/90)were irregular rhythmic arrhythmias, of which 66.7%(38/57)were atrial premature contractions, 23.3%(21/90) were tachyarrhythmias, and 13.3%(12/90)were bradyarrhythmias.Additionally, 80.0%(72/90)of the cases had no typical clinical manifestations.Besides, 37.7%(34/90)of the patients had single infection factor, and 4.4%(4/90)of the patients had infection with perinatal hypoxia asphyxia.The ratio of the premature birth, maternal autoimmune diseases and the tachyarrhythmia were higher in heart failure group than those in normal heart function group(71.4% vs.13.3%, P<0.001; 28.6% vs.3.6%, P=0.006; 100% vs.16.9%, P<0.001). The random forest model showed that the factors of premature delivery and maternal autoimmune disease had the greatest influence on cardiac function, and the analysis of 21 tachyarrhythmias showed that the duration of arrhythmia had the greatest influence on cardiac function. Conclusion:Atrial premature contraction is the most common in neonate with arrhythmia, and with non-typical clinical manifestations.The infection and the infection combined with perinatal asphyxia are the main influencing factors of neonate with arrhythmia.Premature delivery, maternal autoimmune disease and the duration of tachyarrhythmias are the main risk factors of neonatal arrhythmias leading to cardiac dysfunction.
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Objective:To explore the clinical characteristics of neonate with arrhythmia and the potential risk factors for cardiac insufficiency.Methods:Research data were collected from the cases of neonate with arrhythmia from January 2017 to June 2021 at the Neonatology Department at Children′s Hospital Capital Institute of Pediatrics.A retrospective analysis was conducted to summarize the clinical features and analyze the risk factors of arrhythmia leading to cardiac insufficiency.Results:A total of 90 cases were enrolled, with a male to female ratio of 1.43∶1(53∶37), and the median gestational age was 39(37, 40)weeks; with 16(17.8%) premature infants, 74 full-term infants(82.2%), and the median onset age was 3(0, 11)days.In this group, 63.3% cases(57/90)were irregular rhythmic arrhythmias, of which 66.7%(38/57)were atrial premature contractions, 23.3%(21/90) were tachyarrhythmias, and 13.3%(12/90)were bradyarrhythmias.Additionally, 80.0%(72/90)of the cases had no typical clinical manifestations.Besides, 37.7%(34/90)of the patients had single infection factor, and 4.4%(4/90)of the patients had infection with perinatal hypoxia asphyxia.The ratio of the premature birth, maternal autoimmune diseases and the tachyarrhythmia were higher in heart failure group than those in normal heart function group(71.4% vs.13.3%, P<0.001; 28.6% vs.3.6%, P=0.006; 100% vs.16.9%, P<0.001). The random forest model showed that the factors of premature delivery and maternal autoimmune disease had the greatest influence on cardiac function, and the analysis of 21 tachyarrhythmias showed that the duration of arrhythmia had the greatest influence on cardiac function. Conclusion:Atrial premature contraction is the most common in neonate with arrhythmia, and with non-typical clinical manifestations.The infection and the infection combined with perinatal asphyxia are the main influencing factors of neonate with arrhythmia.Premature delivery, maternal autoimmune disease and the duration of tachyarrhythmias are the main risk factors of neonatal arrhythmias leading to cardiac dysfunction.
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Objective:To explore the feasibility of predicting axillary lymph node metastasis of breast cancer using radiomics analysis based on dynamic contrast-enhanced (DCE) MRI.Methods:The retrospective study enrolled 163 patients (163 lesions) with breast cancer diagnosed by core needle biopsy from January 2013 to December 2013 in Peking University First Hospital. The status of axillary lymph nodes in all patients was pathologically confirmed, and they had complete preoperative breast MRI images. Among the 163 patients, 94 patients were confirmed with axillary lymph node metastasis, and 69 patients without axillary lymph node metastasis. They were randomly divided into the training dataset ( n=115) and testing dataset ( n=48) in a 7∶3 ratio. The radiomics analysis was performed in the training dataset, including image preprocessing and labeling, radiomics feature extraction, radiomics model establishment and model predictive performance inspection. Model performance was tested in the testing dataset. Receiver operating characteristic curve and area under curve (AUC) was used to analyze the model prediction performance. Results:Of the 1 075 features extracted from the training dataset, principal component analyses (PCA) features 8, 41 and 67 were selected by random forest classifier. The radiomics model including 3 PCA features reached an AUC of 0.956 (95%CI 0.907-0.988), with sensitivity of 91.2%, specificity of 100% and accuracy of 94.8%. In the testing dataset, the radiomics model including 3 PCA features reached an AUC of 0.767 (95%CI 0.652-0.890), with sensitivity of 80.8%, specificity of 72.7% and accuracy of 77.1%.Conclusion:It is feasible to predict axillary lymph node metastasis using radiomics features based on DCE-MRI of breast cancer.
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Objective:To investigate the regulatory effects of mitofusin 1 (MFN1) on lipopolysaccharide (LPS)-induced Raw264.7 mouse macrophages pyroptosis and to provide reference for further study on the prevention of inflammation and fibrosis caused by macrophage dysfunction.Methods:Raw264.7 mouse macrophages were cultured in vitro and used to construct a model of LPS-induced pyroptosis. CCK-8 staining, PI staining, LDH release assay and Western blot were used to verify the Raw264.7 pyroptosis induced by LPS. MFN1 expression was detected by Western blot. DCFH-DA probe was used to detect the synthesis of total reactive oxygen species (ROS); Mito-SOX was used to detect mitochondrial ROS; JC-1 mitochondrial membrane potential was detected by fluorescence probe to reflect mitochondrial damage. Based on Ubibrowser database, it was predicted that MFN1 could bind to a variety of E3 ubiquitin ligases. Then, immunofluorescence and co-immunoprecipitation (CO-IP) were used to analyze MFN1 ubiquitination. An overexpression plasmid for MFN1 was constructed and transfected into Raw264.7 cells to detect the changes in pyroptosis and mitochondrial function. Results:LPS could induce the pyroptosis of Raw264.7 cells and mitochondrial dysfunction. MFN1 expression was decreased after LPS stimulation. Ubiquitinated MFN1 was detected by CO-IP. Ubiquitination inhibitor MG-132 inhibited LPS-induced expression of pyroptosis-related proteins including NLRP3, Pro-caspase-1, Caspase-1, IL-1β and IL-18 and improved mitochondrial function. MFN1 overexpression relieved the mitochondrial dysfunction and pyroptosis of Raw264.7 cells induced by LPS.Conclusions:The ubiquitination of MFN1 induced by LPS was involved in mitochondrial dysfunction and macrophage pyroptosis, suggesting that MFN1 was a potential target for the treatment of macrophage-induced inflammation and related diseases.
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Objective:To compare the imaging features of renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE3 gene fusion (Xp11.2 RCC) with chromophobe RCC.Methods:From November 2016 to January 2020, 28 patients with Xp11.2 RCC and 28 patients with chromophobe RCC confirmed by pathology were retrospectively analyzed in Peking University First Hospital. All 23 patients underwent preoperative CT examination, and 5 patients underwent routine MRI in each group. The clinical and imaging features were observed and recorded. The CT features including side, location, size, boundary, shape, uniform density, composition (solid, cystic-solid, cystic), hemorrhage, calcification, lymph node metastasis of the lesions and distant metastasis were observed, and the CT value of the solid part of the tumor at each stage was measured. On MRI images, the signal of the lesion in each sequence and enhancement mode were observed. The differences in clinical and imaging characteristics between the 2 groups were compared using independent samples t test or χ 2 test. Results:The Xp11.2 RCC more frequently affected young [(27±10) years] patients, while chromophobe RCC more frequently involved middle-aged [(37±7) years] patients asymptomatically, and the difference was statistically significant ( t=-4.99, P<0.001). The lesion size of Xp11.2 RCC [(5.4±2.2) cm] were significantly smaller than that of chromophobe RCC [(6.9±1.8) cm] ( t=-2.93, P=0.005). There were significant differences in the density and composition of lesions between Xp11.2 RCC and chromophobe RCC (χ 2=4.60, 18.67, P=0.032,<0.001). There were no significant differences in the side, location, boundary, shape, hemorrhage, calcification, fat, lymph node metastasis and distant metastasis between the 2 kind of lesions (all P>0.05). The CT values of solid components in Xp11.2 RCC in cortico-medullary phase and delayed phase were higher than those in chromophobe RCC, and the difference were statistically significant ( t=11.80, 20.15, both P<0.001). Five cases of Xp11.2 RCC showed iso- or slightly hyperintense signal on T 1WI and slightly hypointense signal on T 2WI. Two cases showed delayed enhancement after enhancement, and 3 cases showed a slight decrease in delayed phase enhancement. Conclusion:Compared with chromophobe RCC, Xp11.2 RCC has certain characteristics in imaging manifestations (lesion size, density uniformity, composition, CT value of post-enhanced cortico-medullary phase and delayed phase). Imaging manifestations combining the clinical manifestations (age of onset) are helpful for preoperative diagnosis of Xp11.2 RCC.
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Objective:To explore the feasibility of classification between carcinoma in situ and invasive carcinoma of breast using intratumoral and peritumoral radiomics based on breast dynamic contrast-enhanced (DCE) MRI.Methods:The retrospective study included consecutive invasive breast carcinoma pathological diagnosed by core needle biopsy or surgery from January 2013 to December 2013 and carcinoma in situ of breast diagnosed by surgery from January 2013 to December 2015 in Peking University First Hospital. All patients had pretreatment breast MRI images. A total of 251 cases (251 lesions) were included, with 208 invasive breast carcinoma and 43 carcinoma in situ of breast. They were all females and median age was 53 (23-82) years old. Patients were randomly divided into the training ( n=176) and testing dataset ( n=75) in a 7∶3 ratio. In the training dataset, combined with DCE mask and early enhancement images, intratumoral and peritumoral area were semi-automatic segmentation, and radiomics features were extracted and dimension reduction, finally a prediction model was established. Model performance was tested in the testing dataset. Receiver operating characteristic (ROC) curve and area under curve (AUC) were used to analyze the model prediction performance. Results:The prediction models established by intratumoral, peritumoral and intratumoral combined with peritumoral radiomics had good performance. The AUC of intratumoral, peritumoral and intratumoral combined with peritumoral radiomics prediction models in differentiating breast carcinoma in situ and invasive carcinoma were 0.865, 0.896 and 0.922 in the testing dataset, there was no significant difference in pairwise comparisons ( P>0.05). The sensitivity of intratumoral, peritumoral and intratumoral combined with peritumoral radiomics prediction models were 77.4%, 87.1%, 83.9%, the specificity were 92.3%, 84.6%, 100%, and the accuracy were 80.0%, 85.3%, 86.7%. Conclusion:It is potential feasible for classification between carcinoma in situ and invasive carcinoma of breast using intratumoral and peritumoral radiomics based on breast DCE MRI.
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Objective:To summarize and analyze the clinical characteristics of patients with infective endocarditis (IE) complicated with cerebral hemorrhage.Methods:The clinical data of 15 IE patients with intracerebral hemorrhage diagnosed in the Affiliated Hospital of Xuzhou Medical University from January 2010 to December 2021 were analyzed retrospectively, and their clinical characteristics were analyzed, including the mode of onset, cranial imaging characteristics, associated diseases, echocardiography, hematology, etiology, chest computed tomography (CT), cerebrospinal fluid characteristics, treatment methods and prognosis of patients.Results:Cerebral hemorrhage in IE patients were acute or subacute onset. Head CT scanning showed that cerebral hemorrhage usually occurred in the brain lobe, can be combined with rheumatic heart disease, congenital heart defect or immune system diseases, etc. Ultrasonic cardiogram can be used to determine the location of vegetations in the heart cavity, the damage of the valve and the hemodynamic changes. The hematologic examination showed elevated hemogram and increased erythrocyte sedimentation rate. Staphylococcus aureus or streptococcus viridans were often detected on the etiological examination. Lung infection was often seen on a chest CT, and inflammatory changes were seen in the cerebrospinal fluid. IE was treated with sufficient course of antibiotics and valve replacement with valve damage. The case fatality rate was 3/15.Conclusions:Young patients presented with lobar hemorrhage, headache, fever and rheumatic heart disease should be thought of the possibility of IE combined with cerebral hemorrhage. IE with intracerebral hemorrhage has a poor prognosis and a high mortality.
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The objective of this study is to elucidate the effects of gut microbiome imbalance on impaired cognitive function in schizophrenia patients， and to propose a new approach to improve cognitive impairment in schizophrenia patients. The cognitive impairment of schizophrenic patients is one of the major barriers that hinder patient social reintegration. With the emergence of microbiome-gut-brain axis， many researchers have found that there is a certain relationship between gut microbiome imbalance and impaired cognitive function in schizophrenia patients， so this paper reviews and summarizes such relationship found in previous studies， with a view to informing the exploration of new ways to improve cognitive impairment in schizophrenia patients.
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Objective: To investigate the role of Portulaca oleracea (POL) in promoting revascularization and re-epithelization as well as inhibiting iron aggregation and inflammation of deep tissue pressure injury (DTPI). Methods: The hydroalcoholic extract of POL (P) and aqueous phase fraction of POL (PD) were prepared based on maceration and liquid–liquid extraction. The number of new blood vessels and VEGF-A expression level were assessed using H&E stain and Western blot on injured muscle to examine the role of POL different extracts in vascularization. The iron distribution and total elemental iron of injured muscle were detected using laser ablation inductively coupled plasma mass spectrometry (ICP-MS) and Perls’ staining to determine whether POL extracts can inhibit the iron accumulation. Besides, the ability of POL extracts to promote wound healing by combining re-epithelization time, inflammation degree and collagen deposition area were comprehensively evaluated. Results: In vitro, we observed a significant increase in HUVEC cell viability, migration rate and the number of the tube after P and PD treatment (P < 0.05). In vivo, administration of P and PD impacted vascularization and iron accumulation on injured tissue, evident from more new blood vessels, higher expression of VEGF-A and decreased muscle iron concentration of treatment groups compared with no-treatment groups (P < 0.05). Besides, shorter re-epithelization time, reduced inflammatory infiltration and distinct collagen deposition were associated with administration of P and PD (P < 0.05). Conclusion: POL extract administration groups have high-quality wound healing, which is associated with increased new blood vessels, collagen deposition and re-epithelization, along with decreased iron accumulation and inflammatory infiltration. Our results suggest that that POL extract is beneficial to repair injured muscle after ischemia–reperfusion, highlighting the potential of POL in the DTPI treatment.
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Hyperaldosteronism is a common disease that is closely related to endocrine hypertension and other cardiovascular diseases. Cytochrome P450 11B2 (CYP11B2), an important enzyme in aldosterone (ALD) synthesis, is a promising target for the treatment of hyperaldosteronism. However, selective inhibitors targeting CYP11B2 are still lacking due to the high similarity with CYP11B1. In this study, atractylenolide-I (AT-I) was found to significantly reduce the production of ALD but had no effect on cortisol synthesis, which is catalyzed by CYP11B1. Chemical biology studies revealed that due to the presence of Ala320, AT-I is selectively bound to the catalytic pocket of CYP11B2, and the C8/C9 double bond of AT-I can be epoxidized, which then undergoes nucleophilic addition with the sulfhydryl group of Cys450 in CYP11B2. The covalent binding of AT-I disrupts the interaction between heme and CYP11B2 and inactivates CYP11B2, leading to the suppression of ALD synthesis; AT-I shows a significant therapeutic effect for improving hyperaldosteronism.
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Objective:To explore the expression of long non-coding RNA LINC00630 in bladder cancer cell lines, and to explore the effect of interference with its expression in vitro on the proliferation and migration of bladder cancer cells.Methods:Real-time fluorescent quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of LINC00630 in bladder cancer cell lines 5637, BIU-87, T24, J82 and normal bladder epithelial cell line SV-HUC-1. The bladder cancer cell line with the highest LINC00630 expression was selected for follow-up experiments, then the cell line infected with the control lentivirus was used as the control group, and the cell line infected with the lentivirus that could interfere with the expression of LINC00630 was used as the experimental group. qRT-PCR was used to detect the expression of LINC00630 in the two groups of cells. MTS method and cell scratch test were used to detect the proliferation and migration abilities of cells in the two groups. qRT-PCR was used to detect the expression of neuregulin 1 (NRG1) mRNA in the two groups of cells, and Western blot was used to detect the expressions of NRG1 protein, cell proliferation-related proteins (cyclin D3 and CDK2) and cell migration-related proteins (Vimentin and N-cadherin) in the two groups of cells.Results:Compared with SV-HUC-1 cells (1.05±0.17), the expression of LINC00630 was significantly increased in all bladder cancer cell lines (all P < 0.01), and the expression was highest in J82 cells (relative expression 5.83±0.42). Compared with J82 cells of the control group, the expression of LINC00630 in J82 cells of the experimental group decreased (0.18±0.02 vs. 1.00±0.05, t=14.36, P < 0.01); from day 2 of transfection, the cell proliferation activity of the experimental group was lower than that of the control group (all P < 0.05). The cell scratch closure rate of the experimental group was lower than that of the control group [(27.4±7.1)% vs. (66.0±5.4)%, t = 4.31, P < 0.01]. Therelative expression of NRG1 mRNA in the experimental group was lower than that in the control group (0.34±0.03 vs. 1.07±0.24, t = 2.99, P < 0.05). Compared with the control group, the expressions of NRG1 protein, cell proliferation-related proteins and cell migration-related proteins in the experimental group were reduced. Conclusions:LINC00630 is up-regulated in bladder cancer cell lines, and interference with LINC00630 may inhibit the proliferation and migration of J82 cells by down-regulating the expression of NRG1 gene. LINC00630 may be a new molecular target for the treatment of bladder cancer.
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Objective:To observe the expression of microRNA (miRNA, miR) -7850 in renal cancer tissues, and to explore the effect of miR-7850 on the proliferation and migration of renal cancer cells and on the regulation of serine proteinase inhibitor B3 (SERPINB3) gene expression.Methods:Real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-7850 in renal cancer tissues and renal cancer cell lines. The renal cell carcinoma cell line with the lowest expression of miR-7850 was selected, and the negative control sequence (miR-NC) and miR-7850 mimics were transfected into renal cell carcinoma cells by Lipofectamine 2000 transfection reagent, respectively, which were defined as miR-NC group and miR-7850 group. qRT-PCR was used to detect the expression of miR-7850 in transfected renal cancer cells. The cell proliferation and migration ability after transfection were detected by cell counting kit-8 (CCK-8) method and transwell experiment. Bioinformatics prediction and dual luciferase reporter gene experiments were used to verify the target gene of miR-7850. qRT-PCR and Western blot were used to detect the expression of target genes in renal cancer cells after transfection.Results:Compared with adjacent tissues (5.95±0.44), the expression of miR-7850 in kidney cancer tissues (1.19±0.33) was lower ( P<0.01). Compared with immortalized proximal renal tubular epithelial cells (1.01±0.07), the expression of miR-7850 was lower in renal cancer cell lines ( P<0.05), and the lowest in A498 cells (0.13±0.01) ( P<0.01). The expression of miR-7850 in the miR-7850 group (7.46±0.93) was significantly higher than that in the miR-NC group (1.01±0.08) ( P<0.01), indicating successful transfection. Compared with the miR-NC group, the cell proliferation ability of the miR-7850 group was significantly reduced ( P<0.05). The number of migrating cells in miR-NC group and miR-7850 group were (139.50±12.31) and (75.09±16.05) cells, respectively, and the cell migration ability in miR-7850 group decreased significantly ( P<0.01). Bioinformatics technology shows that the target gene of miR-7850 was SERPINB3. The dual luciferase reporter gene experiment confirmed that miR-7850 can target the SERPINB3 gene ( P<0.05). Compared with the miR-NC group, the expression of SERPINB3 in cells of miR-7850 group was significantly reduced ( P<0.05), as well as the CDK4, CyclinD, Snail and Vimentin. Conclusions:miR-7850 is lowly expressed in renal cancer tissues and cell lines. miR-7850 can inhibit the proliferation and migration of renal cancer A498 cells, which may be related to its inhibition of SERPINB3 gene expression.
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Objective:To analyze the expression of long non-coding RNA (lncRNA) ZFPM2-AS1 in bladder cancer tissues and cell lines, and to observe the effect of down-regulating ZFPM2-AS1 on the migration and proliferation of bladder cancer cells and explore its molecular mechanism.Methods:Real-time quantitative fluorescent polymerase chain reaction (qRT-PCR) was used to detect the expression of ZFPM2-AS1 in 51 pairs of bladder cancer tissues and adjacent tissues, bladder cancer cell lines (J82, 5637, BIU-87, T24) and human normal bladder epithelial cells SV-HUC-1. The bladder cancer cells with the highest ZFPM2-AS1 expression were selected and transfected with the small interfering siRNA-ZFPM2-AS1 plasmid and the negative control plasmid, respectively, and defined as the experimental group and the control group. qRT-PCR was used to detect the expression of ZFPM2-AS1 in two groups of cells. Transwell migration test and tetramethylazozole blue (MTT) method were used to detect the cell migration ability and proliferation ability of the two groups. qRT-PCR was used to detect the expression of Up-frameshift mutant 1 (UPF1) mRNA in two groups of cells. Western blot was used to detect the expression of UPF1 and mTOR signaling pathway proteins in the two groups of cells.Results:The expression of ZFPM2-AS1 in bladder cancer tissues was significantly higher than that in adjacent tissues ( P<0.01). The expression of ZFPM2-AS1 in bladder cancer cell lines was significantly higher than that in human normal bladder epithelial cells ( P<0.01), and ZFPM2-AS1 had the highest expression in BIU-87 cells ( P<0.01). Compared with the control group, the expression of ZFPM2-AS1 in BIU-87 cells in the experimental group was significantly reduced [(1.01±0.06) vs (0.16±0.04), t=12.28, P<0.01]. Compared with the control group, the migration ability of BIU-87 cells in the experimental group was decreased ( P<0.05), and the proliferation ability of BIU-87 cells was significantly decreased from the second day ( P<0.05). Compared with the control group, UPF1 mRNA expression in BIU-87 cells in the experimental group was significantly decreased [(1.00±0.02) vs (0.28±0.04), t=15.49, P<0.01]. Western blot results showed that UPF1 protein expression and mammalian rapamycin target protein (mTOR), GRB2, IRS1 and p-PI3K signal pathway protein expression were decreased in BIU-87 cells. Conclusions:ZFPM2-AS1 is highly expressed in bladder cancer tissues and cell lines. Down-regulating ZFPM2-AS1 can inhibit the migration and proliferation of BIU-87 cells. The molecular mechanism may be related to the inhibition of UPF1 gene expression.
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Objective:To explore the molecular mechanism of microRNA (miRNA, miR)-1914-3p regulating the expression of ARL4C and affecting the invasion and proliferation of renal cancer cells.Methods:Real-time fluorescent quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression level of miR-1914-3p in tumor tissues and adjacent tissues of 53 renal cancer patients, 4 types of renal cancer cell lines (ACHN, OS-RC-2, 786-O, A498) and normal proximal renal tubular epithelial cell line (HK-2). The nonsense sequence (NC) and miR-1914-3p mimic were transiently transfected into renal cancer cells with the lowest miR-1914-3p expression by liposome method, namely the NC group and miR-1914-3p group. qRT-PCR was used to detect the expression level of miR-1914-3p in transfected cells. Transwell invasion test and cell counting kit-8 (CCK-8) were used to detect the invasion and proliferation ability of each group of cells. Bioinformatics software and dual luciferase gene report experiment were used to predict and test the targeted regulation mechanism of miR-1914-3p on target genes. qRT-PCR and Western blot was conducted to analyze the target gene expression level in cells of each group.Results:The expression level of miR-1914-3p in renal cancer tissue was significantly lower than that in adjacent tissues ( P<0.01). The expression level of miR-1914-3p in renal cancer cell lines was significantly lower than that in HK-2 cell lines ( P<0.01), and the expression of miR-1914-3p in OS-RC-2 cells was the lowest ( P<0.01). The expression of miR-1914-3p in the NC group and the miR-1914-3p group were (1.04±0.17) and (11.40±0.91), respectively. The expression level of miR-1914-3p in the miR-1914-3p group was significantly increased ( P<0.01), indicating that the transfection was successful. Overexpression of miR-1914-3p can significantly inhibit the invasion ( P<0.01) and proliferation ( P<0.05) of renal cancer OS-RC-2 cells. Dual luciferase gene report experiment indicated that the target gene of miR-1914-3p may be ADP-ribosylation factor-like 4C (ARL4C); miR-1914-3p can significantly inhibit the luciferase activity of wild-type ARL4C-3′UTR ( P<0.01). Overexpression of miR-1914-3p decreased the expression of ARL4C mRNA and protein in OS-RC-2 cells ( P<0.01), and decreased the expression of cell invasion phenotype proteins (Snail, Slug) and cell proliferation phenotype proteins (Mcm2, Mcm7) ( P<0.01). Conclusions:miR-1914-3p is low-expressed in renal cell carcinoma. It inhibits the invasion and proliferation of renal cell carcinoma OS-RC-2 cells through targeted interference with the expression of the oncogene ARL4C, and participates in the occurrence and development of renal cell carcinoma.
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Objective:To investigate the clinical efficacy of uterine compression suture in the treatment of postpartum hemorrhage resulting from uterine atony.Methods:100 patients with postpartum hemorrhage due to uterine atony who received treatment between May 2017 and May 2018 in the First People's Hospital of Yongkang were included in this study. They were randomly assigned to undergo either conventional uterine suture (control group, n = 50) or uterine compression suture (observation group, n = 50). Clinical efficacy was compared between the observation and control groups. Results:Total effective rate in the observation group was significantly higher than that in the control group [94.0% (47/50) vs. 68.0% (34/50), χ2 = 12.421, P < 0.01]. There was no significant difference in operative time between observation and control groups [(62.99 ± 10.87) minutes vs. (60.98 ± 8.12) minutes, t = 1.048, P > 0.05]. The amount of blood loss within 2 and 24 hours postpartum, abdominal circumference, and uterine height in the observation group were (216.85 ± 16.85) mL, (356.19 ± 25.71) mL, (98.56 ± 5.86) cm and (35.17 ± 2.33) cm respectively, which were significantly less or lower than those in the control group [(485.29 ± 28.41) mL, (596.38 ± 34.18) mL, (108.59 ± 2.65) cm, and (38.45 ± 4.19) cm, t = 85.652, 65.325, 16.584, 3.256, all P < 0.05]. The incidence of complications in the observation group was significantly lower than that in the control group [4.0% (2/50) vs. 28.0% (14/50), χ2 = 12.032, P < 0.01]. Conclusion:Uterine compression suture for the treatment of postpartum hemorrhage resulting from uterine atony has greater clinical efficacy and leads to lower incidence of complications than conventional suture technique.
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Objective:To explore the establishment of a cluster intervention strategy by multi-criteria decision analysis (MCDA) to provide a basis for the early removal of indwelling catheters in severe neurological patients.Methods:Through literature retrieval and MCDA, the catheter cluster intervention strategy was constructed, and the expert consultation was adopted to finally form 7 item cluster intervention strategies. The convenience sampling method was used to select 122 patients with severe neurological diseases as the research objects. A total of 61 patients with indwelling catheters from November 2018 to April 2019 were selected as the control group, and routine nursing care was performed according to indwelling catheters. A total of 61 patients with indwelling catheters from May 2019 to October 2019 were selected as the intervention group to compare the success rate of removing catheters, the number of days of indent catheters and the incidence of catheter-associated urinary tract infection ( CAUTI) in the two groups, as well as to analyze the indicators related to indent catheters in the intervention group with different diagnoses. Results:CAUTI incidence, successful catheter removal rate, indwelling days of catheter in the intervention group were 39.3% (24/61), 32.79% (20/61), 17 (14,22) days, which were significantly higher than 59.0% (36/61), 8.19% (5/61), 21 (15, 27) days in the control group, and the difference was statistically significant (χ 2 values were 4.723, 11.775, Z value was -9.211, P<0.05 or 0.01); In the intervention group, stroke patients′ indwelling time of catheter were 7-20 days, and the highest success rate of removing urinary catheters 36.6% (15/41), compared with other diseases, the difference was statistically significant ( Z values were -2.448, -2.109, P<0.05). Conclusion:MCDA construction of early catheter removal strategy can significantly shorten the indwelling time of the catheter in patients with severe neurological diseases, improve the success rate of early catheter extubation, reduce the CAUTI rate, to provide evidence-based basis for clinical nursing.