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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 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 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 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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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 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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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 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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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 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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Visual object recognition in humans and nonhuman primates is achieved by the ventral visual pathway (ventral occipital-temporal cortex, VOTC), which shows a well-documented object domain structure. An on-going question is what type of information is processed in the higher-order VOTC that underlies such observations, with recent evidence suggesting effects of certain visual features. Combining computational vision models, fMRI experiment using a parametric-modulation approach, and natural image statistics of common objects, we depicted the neural distribution of a comprehensive set of visual features in the VOTC, identifying voxel sensitivities with specific feature sets across geometry/shape, Fourier power, and color. The visual feature combination pattern in the VOTC is significantly explained by their relationships to different types of response-action computation (fight-or-flight, navigation, and manipulation), as derived from behavioral ratings and natural image statistics. These results offer a comprehensive visual feature map in the VOTC and a plausible theoretical explanation as a mapping onto different types of downstream response-action systems.
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Objective:To discuss the clinical characteristics and genetic diagnosis of fetal familial hemophagocytic lymphohistiocytosis (FHL).Methods:Clinical data of a case of fetal FHL from Children's Hospital, Capital Institute of Pediatrics was analyzed, and related FHL cases at home and abroad were retrieved from PubMed, CNKI, and Wanfang databases using terms including "fetus", "neonate", and "familial hemophagocytic lymphohistiocytosis", from the establishment of the database to January 3, 2021, to summarize the characteristics of this disease.Results:This index case was found with fetal splenomegaly, free fluid in the abdominal cavity, and enlargement of the ventricle at 39 +3 weeks of gestation, and presented with fever, tachypnea, hepatosplenomegaly, skin ecchymosis and petechia, and lymphadenectasis after birth. Laboratory examination revealed pancytopenia, abnormal liver function, elevated ferritin and triglyceride, and decreased fibrinogen levels. CD107a excitation experiment showed decreased degranulation function of NK cell (ΔCD107a<5%). Hemophagocytosis was observed in the bone marrow smear. Genomic DNA sequence analysis demonstrated compound heterozygous mutations of c.118-308C>T and c.3002T>C in the UNC13D gene. All the above findings led to the diagnosis of FHL3. Despite chemotherapy with dexamethasone and cyclosporin, and symptomatic treatment after admission without hematopoietic stem cell transplantation, the baby died on day 52. A total of 15 papers related to fetal FHL, including 20 infants, were retrieved. Among these 21 cases (including the index case), the main clinical symptoms were fetal edema and hepatosplenomegaly, which may be accompanied by fetal distress and increased amniotic fluid volume, and postnatal fever, dyspnea, rash, and central nervous system involvement. Laboratory and imaging examination results were consistent with the diagnostic criteria for hemophagocytic hyperplasia. As far as we know, the reported fetal FHL gene mutations were PRF1 (FHL2) and UNC13D gene mutation (FHL3), in which reduced expression of perforin and granzyme can be detected, respectively. Dexamethasone, cyclosporin, etoposide, and other chemotherapy and symptomatic treatment are the primary treatments currently, and alternative therapies include intrauterine chemotherapy in the third trimester and postnatal hematopoietic stem cell transplantation. Among the 21 cases, including the index case, intrauterine death occurred in four cases, 13 children died at different times after birth, and only four children survived, among which the eldest one was 12 years old. Conclusions:FHL is a condition with atypical early signs, high mortality rate and treatment difficulties. Fetal FHL should be considered in differential diagnosis in fetuses with edema or hepatosplenomegaly besides hemolysis, infection, autoimmune diseases, and hereditary problems. Therefore, with immunotechnology and gene sequencing, early diagnosis and treatment can be prompted to improve the prognosis of this group of population.
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Objective:To evaluate the accuracy of variation of carotid artery hemodynamic parameters combined with passive leg raising (PLR) test in predicting supine hypotension syndrome (SHS) after spinal anesthesia in the patients undergoing cesarean section.Methods:Sixty-four parturients who were at full term with a singleton fetus, at 37-42 weeks of gestation, aged 18-40 yr, with body mass index of 18-30 kg/m 2, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, undergoing elective cesarean section, were enrolled in this study.The variation of carotid artery diameter (ΔD), variation of velocity time integral (ΔVTI), and variation of carotid blood flow (ΔCBF) before and after PLR were measured using ultrasound.Patients were divided into SHS group and non-SHS group (NSHS group) according to whether SHS after spinal anesthesia occurred.Pearson correlation was used to analyze the correlation between ΔD, ΔVTI, ΔCBF and systolic blood pressure (SBP) after spinal anesthesia.The receiver operating characteristic curve was used to assess the accuracy of ΔD, ΔVTI and ΔCBF in predicting SHS. Results:ΔVTI was negatively correlated with SBP after spinal anesthesia ( r=-0.539, P<0.01), ΔCBF was negatively correlated with SBP after spinal anesthesia ( r=-0.475, P<0.05), and ΔD had no correlation with SBP after spinal anesthesia in group SHS ( P>0.05). The critical values of ΔCBF, ΔVTI, and ΔD combined with PLR in predicting SHS after spinal anesthesia were 15.5%, 10.1%, and 6.0%, respectively, the sensitivity was 92.9%, 57.1%, and 96.4%, respectively, and the specificity was 53.1%, 81.2%, and 75.0%, respectively, and the areas under the curve were 0.873, 0.681 and 0.846, respectively. Conclusion:The ultrasound-measured ΔCBF and ΔD of carotid artery combined with PLR can be used as a reliable method to predict SHS after spinal anesthesia in the patients undergoing cesarean section, and the ΔCBF combined with PLR has a higher accuracy.
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Objective:To evaluate the role of silent information regulator 1 (SIRT1) in electroacupuncture (EA)-induced reduction of central post-stroke pain (CPSP) and the relationship with nod-like receptor pyrin domain containing 3 (NLRP3) in rats.Methods:Fifty SPF healthy male Sprague-Dawley rats, aged 6 weeks, weighing 180-220 g, were divided into 5 groups ( n=10 each) using a random number table method: sham operation group (group Sham), CPSP group, CPSP+ sham EA group (group SEA), CPSP+ EA group (group EA) and CPSP+ EA+ SIRT1 inhibitor EX527 group (group EX527). Type Ⅳ collagenase was injected into the right ventral posterolateral nucleus to establish the model of CPSP in CPSP, SEA, EA and EX527 groups.At 24 h after the model was established successfully, 30 min EA (frequency 2/15 Hz) stimulation of Neiguan, Renzhong and Sanyinjiao was performed once a day for 5 consecutive days in EA group.EA was performed at the points 5 mm lateral to the acupoints of Neiguan, Renzhong and Sanyinjiao in group SEA, and the other procedures were similar to those previously described in group EA.SIRT1 inhibitor EX527 5 mg/kg was injected intraperitoneally at 30 min before EA stimulation in group EX527, and the other procedures were similar to those previously described in group EA.At 1 day before the establishment of model (T 0) and at 1, 3 and 5 days after the establishment of model (T 1-3), the thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) were measured.The animals were then sacrificed and brain tissues were taken for determination of the expression of SIRT1, NLRP3 and interleukin (IL)-18 and IL-1β. Results:Compared with Sham group, the TWL was significantly shortened and the MWT was decreased at T 1-3, the expression of SIRT1 was down-regulated, and the expression of NLRP3, IL-18 and IL-1β was up-regulated in CPSP, SEA, EA and EX527 groups ( P<0.05). Compared with CPSP group, the TWL was significantly prolonged and the MWT was increased at T 1-3, the expression of SIRT1 was up-regulated, and the expression of NLRP3, IL-18 and IL-1β was down-regulated in EA group ( P<0.05), and no significant change was found in the parameters mentioned above in group SEA ( P>0.05). Compared with EA group, the TWL was significantly shortened and the MWT was decreased at T 1-3, the expression of SIRT1 was down-regulated, and the expression of NLRP3, IL-18 and IL-1β was up-regulated in EX527 group ( P<0.05). Conclusion:SIRT1 is involved in the process of EA-induced reduction of CPSP, which is related to inhibiting NLRP3 expression in rats.
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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.