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Objective: To explore the influencing factors of pregnancy-induced hypertensive disorders in pregnancy (HDP) with organ or system impairment in pregnant women, and to analyze and compare the differences of HDP subtypes in different regions of China. Methods: A total of 27 680 pregnant women with HDP with complete data from 161 hospitals in 24 provinces, autonomous regions and municipalities were retrospectively collected from January 1, 2018 to December 31, 2018. According to their clinical manifestations, they were divided into hypertension group [a total of 10 308 cases, including 8 250 cases of gestational hypertension (GH), 2 058 cases of chronic hypertension during pregnancy] and hypertension with organ or system impairment group [17 372 cases, including 14 590 cases of pre-eclampsia (PE), 137 cases of eclampsia, 2 645 cases of chronic hypertension with PE]. The subtype distribution of HDP in East China (6 136 cases), North China (4 821 cases), Central China (3 502 cases), South China (8 371 cases), Northeast China (1 456 cases), Southwest China (2 158 cases) and Northwest China (1 236 cases) were analyzed. By comparing the differences of HDP subtypes and related risk factors in different regions, regional analysis of the risk factors of HDP pregnant women with organ or system impairment was conducted. Results: (1) The proportions of HDP pregnant women with organ or system impairment in Northeast China (79.05%, 1 151/1 456), Central China (68.42%, 2 396/3 502) and Northwest China (69.34%, 857/1 236) were higher than the national average (62.76%, 17 372/27 680); the proportions in North China (59.18%, 2 853/4 821), East China (60.85%, 3 734/6 136) and South China (59.56%, 4 986/8 371) were lower than the national average, and the differences were statistically significant (all P<0.05). (2) Univariate analysis showed that the proportions of primiparas, non-Han, non-urban household registration, irregular prenatal examination and PE history in the hypertension with organ or system impairment group were higher than those in the hypertension group, and the differences were statistically significant (all P<0.05). Multivariate logistic regression analysis showed that primiparas, non-Han, non-urban household registration, irregular prenatal examination and PE history were independent risk factors for HDP pregnant women with organ or system impairment (all P<0.05). (3) Primipara: the rates of primipara in Northeast China, North China and Southwest China were higher than the national average level, while those in South China, Central China and Northwest China were lower than the national average level. Non-Han nationality: the rates of non-Han nationality in Northeast China, North China and Northwest China were higher than the national average, while those in East China, South China and Central China were lower than the national average. Non-urban household registration: the rates of non-urban household registration in Northeast China, North China, and Southwest China were lower than the national average, while those in East China, Central China were higher than the national average. Irregular prenatal examination: the rates of irregular prenatal examination in North China, South China and Southwest regions were lower than the national average level, while those in Northeast China, Central China and Northwest China were higher than the national average level. History of PE: the incidence rates of PE in Northeast China, North China, South China and Southwest China were lower than the national average level, while those in Central China and Northwest China were higher than the national average level. Conclusions: Primiparas, non-Han, non-urban household registration, irregular prenatal examination, and PE history are risk factors for HDP pregnant women with organ or system impairment. Patients in Northeast, Central and Northwest China have more risk factors, and are more likely to be accompanied by organ or system function damage. It is important to strengthen the management of pregnant women and reduce the occurrence of HDP.
Subject(s)
Humans , Pregnancy , Female , Hypertension, Pregnancy-Induced/diagnosis , Retrospective Studies , Pre-Eclampsia/epidemiology , Risk Factors , IncidenceABSTRACT
Objective: To describe the gene mutation profile of newly diagnosed pediatric B-acute lymphoblastic leukemia (B-ALL) and analyze its effect on minimal residual disease (MRD). Methods: A total of 506 newly diagnosed B-ALL children treated in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from September 2018 to July 2021 were enrolled in this retrospective cohort study. The enrolled children were divided into MRD ≥1.00% group and <1.00% group according to MRD results on the 19th day since chemotherapy, and MRD ≥0.01% group and <0.01% group according to MRD results on the 46th day. Clinical characteristics and gene mutations of two groups were compared. Comparisons between groups were performed with chi-square test or Fisher's exact test. Independent risk factors of MRD results on the 19th day and the 46th day were analyzed by Logistic regression model. Results: Among all 506 patients, there were 318 males and 188 females. On the 19th day, there were 114 patients in the MRD ≥1.00% group and 392 patients in the MRD <1.00% group. On the 46th day, there were 76 patients in the MRD ≥0.01% group and 430 patients in the MRD <0.01% group. A total of 187 gene mutations were detected in 487 (96.2%) of 506 children. The most common gene mutations were signal transduction-related KRAS gene mutations in 111 cases (22.8%) and NRAS gene mutations in 99 cases (20.3%). Multivariate analysis showed that PTPN11 (OR=1.92, 95%CI 1.00-3.63), KMT2A (OR=3.51, 95%CI 1.07-11.50) gene mutations and TEL-AML1 (OR=0.48, 95%CI 0.27-0.87), BCR-ABL1 (OR=0.27, 95%CI 0.08-0.92) fusion genes and age >10 years (OR=1.91, 95%CI 1.12-3.24) were independent influencing factors for MRD ≥1.00% on the 19th day. BCORL1 (OR=2.96, 95%CI 1.18-7.44), JAK2 (OR=2.99, 95%CI 1.07-8.42) and JAK3 (OR=4.83, 95%CI 1.50-15.60) gene mutations and TEL-AML1 (OR=0.43, 95%CI 0.21-0.87) fusion gene were independent influencing factors for MRD ≥0.01% on the 46th day. Conclusions: Children with B-ALL are prone to genetic mutations, with abnormalities in the RAS signaling pathway being the most common. Signal transduction related PTPN11, JAK2 and JAK3 gene mutations, epigenetic related KMT2A gene mutation and transcription factor related BCORL1 gene mutation are independent risk factors for MRD.
Subject(s)
Child , Female , Male , Humans , High-Throughput Nucleotide Sequencing , Neoplasm, Residual/genetics , Retrospective Studies , Genomics , Precursor Cell Lymphoblastic Leukemia-LymphomaABSTRACT
OBJECTIVE@#To establish HL-60 cells and adriamycin resistant HL-60 cells (H-60/ADR) in which the expression of homologous box gene 1 (SIX1) was inhibited, and investigate the effect of inhibiting the expression of SIX1 on the drug resistance.@*METHODS@#Lentivirus was used to transfect HL-60 and HL-60/ADR cells, and the cell lines stably inhibiting the expression of SIX1 were screened by puromycin. CCK-8 assay was used to detect the proliferation ability of cells in each group, apoptosis kit was used to detect the cell apoptosis, and real-time quantitative PCR was used to detect the expression level of drug-resistant related genes.@*RESULTS@#HL-60 and HL-60/ADR stably transfected cell lines with down-regulation of SIX1 expression were successfully constructed. Compared with control group, the inhibition of SIX1 expression significantly inhibited the proliferation of HL-60 and HL-60/ADR cells (P <0.05), increased the apoptosis rate (P <0.05), and the sensitivity of cells to adriamycin increased after inhibition of SIX1 expression.@*CONCLUSION@#Inhibition of SIX1 expression can improve cell sensitivity to adriamycin, and its role in reversing drug resistance may be related to the promotion of apoptosis gene expression.
Subject(s)
Humans , HL-60 Cells , Drug Resistance, Neoplasm/genetics , Leukemia, Myeloid, Acute , Doxorubicin/pharmacology , Apoptosis , Cell Proliferation , Homeodomain Proteins/geneticsABSTRACT
Objective: To construct a prediction model of pathologic complete response (pCR) in locally advanced rectal cancer patients who received programmed cell death protein-1 (PD-1) antibody and total neoadjuvant chemoradiotherapy by using radiomics based on MR imaging data and to investigate its predictive value. Methods: A clinical diagnostic test study was carried out. Clinicopathalogical and radiological data of 38 patients with middle-low rectal cancer who received PD-1 antibody combined with total neoadjuvant chemoradiotherapy and underwent TME surgery from January 2019 to September 2021 in our hospital were retrospectively collected. Among 38 patients, 23 were males and 15 were females with a median age of 68 (47-79) years and 13 (34.2%) a chieved pCR. These 38 patients were stratified and randomly divided into the training group (n=26) and test group (n=12) for modeling. All the patients underwent rectal MRI before treatment. The clinical, imaging and radiomics features of all the patients were collected, and the clinical feature model and radiomics model were constructed. The receiver operating characteristic (ROC) curves of each model were drawn, and the constructed model was evaluated through the area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value and negative predictive value. Results: There were no significant differences in age, gender, primary location of tumor and postoperative pathology between the two groups (all P>0.05). Forty-one features were extracted from region of interest in each modality, including 9 first-order features, 24 gray level co-occurrence matrix features and 8 shape features. From 38 patients, 41 features were extracted from each imaging modality of baseline and preoperative DWI and T2WI images, totally 164 features. Only 4 features were preserved after correlation analysis between each pair of features and t-test between pCR and non-pCR subjects. After LASSO cross validation, only the first-order skewness of the baseline DWI image before treatment and the volume in the baseline T2WI image before treatment were retained. The area under the curve, sensitivity, specificity, positive and negative predictive values of the prediction model established by applying these two features in the training group and the test group were 0.856 and 0.844, 77.8% and 100.0%, 88.2% and 75.0%, 77.8% and 66.7%, 88.2% and 100.0%, respectively. The decision curve analysis of the radiomics model showed that the strategy of this model in predicting pCR was better than that in treating all the patients as pCR and that in treating all the patients as non-pCR. Conclusion: The pCR prediction model for rectal cancer patients receiving PD-1 antibody combined with total neoadjuvant radiochemotherapy based on MRI radiomics has the potential to be used in clinical screening or rectal cancer patients who can be spared from radical surgery.
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Antibodies/therapeutic use , Magnetic Resonance Imaging/methods , Neoadjuvant Therapy/methods , Programmed Cell Death 1 Receptor , Rectal Neoplasms/therapy , Retrospective StudiesABSTRACT
Objective To testify the link between the increase of inducible nitric oxide synthase (iNOS) and monocarboxylate transporter 1 (MCT1) expression in the M1 phenotype microglia under ischemic condition. Methods Photothrombosic ischemia stroke model was applied in 6 mice. BV2 cells were treated with low glucose medium contained 5mmol/L glucose for 2 hours. Immunofluorescent staining and Western blotting were used to check the responses from microglia in the mouse brains subjected to ischemia and BV2 cells were treated with low-glucose treatment. Application of RNA interference or plasmid transfection were used to regulate the MCT1 expression in BV2 cells. Results The expression levels of iNOS, MCT1 and arginase-1 (ARG1) increased in the ischemic side compared to the non-ischemic side of mice brain(P<0.01). In the BV2 cells exposed to low-glucose condition, iNOS and MCT1 levels increased(P<0.001), whereas ARG1 level decreased(P<0.01). RNA interference interfered the expression of MCT1 and then decreased the iNOS expression(P<0.01), while overexpression of MCT1 through plasmid transfection increased iNOS expression(P<0.01), while the ARG1 expressions in both conditions were not changed significantly. Conclusion After microglia polarized into inflammatory phenotype during ischemia period, iNOS production is related with MCT1 expression, and MCT1 is in the upstream of iNOS pathway.
ABSTRACT
Farnesoid X receptor (FXR) has been identified as an inhibitor of platelet function and an inducer of fibrinogen protein complex. However, the regulatory mechanism of FXR in hemostatic system remains incompletely understood. In this study, we aimed to investigate the functions of FXR in regulating antithrombin III (AT III). C57BL/6 mice and FXR knockout (FXR KO) mice were treated with or without GW4064 (30 mg/kg per day). FXR activation significantly prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT), lowered activity of activated factor X (FXa) and concentrations of thrombin-antithrombin complex (TAT) and activated factor II (FIIa), and increased level of AT III, whereas all of these effects were markedly reversed in FXR KO mice. In vivo, hepatic AT III mRNA and protein expression levels were up-regulated in wild-type mice after FXR activation, but down-regulated in FXR KO mice. In vitro study showed that FXR activation induced, while FXR knockdown inhibited, AT III expression in mouse primary hepatocytes. The luciferase assay and ChIP assay revealed that FXR can bind to the promoter region of AT III gene where FXR activation increased AT III transcription. These results suggest FXR activation inhibits coagulation process via inducing hepatic AT III expression in mice. The present study reveals a new role of FXR in hemostatic homeostasis and indicates that FXR might act as a potential therapeutic target for diseases related to hypercoagulation.
Subject(s)
Animals , Mice , Antithrombin III , Blood Coagulation , Hepatocytes , Liver , Mice, Inbred C57BL , Mice, Knockout , Receptors, Cytoplasmic and Nuclear/geneticsABSTRACT
This study investigated the differential mechanisms of Rehmanniae Radix and Rehmanniae Radix Praeparata in improving diabetes in mice through AMPK-mediated NF-κB/NLRP3 signaling pathway. The diabetic mouse model was established with high-fat diet coupled with streptozotocin(STZ, intraperitoneal injection, 100 mg·kg~(-1), once a day for three consecutive days), after which the mice were randomly divided into model group, low-dose(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix groups, low-dose(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix Praeparata groups, catalpol group(250 mg·kg~(-1)), 5-hydroxymethylfurfural(5-HMF) group(250 mg·kg~(-1)), metformin group(250 mg·kg~(-1)), with the normal group also set. The organ indexes of heart,liver, spleen, lung, kidney and pancreas were calculated after four weeks of administration. The pathological changes and fibrosis of pancreas, kidney and liver in mice were observed by hematoxylin-eosin(HE) staining and Masson staining. Western blot was used to determine the expression levels of Toll-like receptor-4(TLR4), nuclear factor-κB(NF-κB), Nod-like receptor protein 3(NLRP3),interleukin-1β(IL-1β), adenosine monophosphate-activated protein kinase(AMPK), phosphorylated AMPK(p-AMPK) in the pancreas, kidney and liver of mice. Compared with the model group, the administration groups witnessed significant decrease in the liver,spleen, kidney, pancreas and fat indexes of diabetic mice, and there was no significant difference in heart and lung indexes. The pathological states and fibrosis of pancreatic, kidney and liver tissues were significantly improved after administration. Additionally, the expression levels of TLR4, NF-κB and NLRP3 in pancreas, kidney and liver of diabetic mice were significantly lowered. The expression levels of p-AMPK/AMPK were enhanced significantly in kidney and liver of mice in Rehmanniae Radix group while in pancreas, kidney and liver in Rehmanniae Radix Praeparata group. This suggests that Rehmanniae Radix and Rehmanniae Radix Praeparata differ in the mechanism of regulating energy metabolism of multiple organs and thereby exerting anti-inflammatory effects to alleviate symptoms of diabetic mice.
Subject(s)
Animals , Mice , AMP-Activated Protein Kinases/genetics , Diabetes Mellitus, Experimental/drug therapy , Diet, High-Fat/adverse effects , NF-kappa B/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein , Plant Extracts , Rehmannia , Signal Transduction , StreptozocinABSTRACT
OBJECTIVE@#To investigate the effect of glycolytic enzyme pyruvate kinase type 2 (PKM2) on the proliferation and apoptosis of human leukemia HL-60 cells.@*METHODS@#si-PKM2 plasmid was transfected into HL-60 cells (set as si-PKM2 group), and blank vector transfected cells were set as control group (si-Ctl group). The expression levels of PKM2 mRNA and protein in si-Ctl group and si-PKM2 group were detected by RT-qPCR and Western blot. CCK-8 cell detection kit was used to detect the proliferation ability of the cells in the two groups. Flow cytometry was used to detect the changes of cell cycle and apoptosis. Western blot and RT-qPCR were used to detect the changes of p-Akt and p-mTOR protein levels in PI3K/Akt/mTOR signaling pathway and the changes of glycolysis-related mRNA levels of the cells in the two groups. The changes in glucose consumption and lactic acid production of the cells were assayed. Over expressed PKM2, HL-60 cells were treated with PI3K inhibitor LY294002 or galactose, the changes in cell proliferation ability, cell cycle and apoptosis, as well as changes in glucose consumption and lactic acid production were detected.@*RESULTS@#Interfered by si-PKM2, mRNA and protein levels of PKM2 in si-PKM2 group significantly decreased, and proliferation ability of the cells was also reduced (P<0.05). After PKM2 knockdown, the cells were significantly blocked at G@*CONCLUSION@#PKM2 knockdown can inhibit the proliferation and induce apoptosis of HL-60 cells, and its molecular mechanism may be related to the PKM2-mediated PI3K/Akt/mTOR-glycolysis, which suggesting that PKM2 may serve as a molecular target for the prevention and treatment of leukemia.
Subject(s)
Humans , Apoptosis , Cell Proliferation , Glycolysis , Phosphatidylinositol 3-Kinases/metabolism , Pyruvate KinaseABSTRACT
Objective: Total neoadjuvant chemoradiotherapy is one of the standard treatments for locally advanced rectal cancer. This study aims to investigate the safety and feasibility of programmed cell death protein 1 (PD-1) antibody combined with total neoadjuvant chemoradiotherapy in the treatment of locally advanced middle-low rectal cancer with high-risk factors. Methods: A descriptive cohort study was conducted. Clinicopathological data of 24 patients with locally advanced middle-low rectal cancer with high-risk factors receiving PD-1 antibody combined with neoadjuvant chemoradiotherapy in Gastrointestinal Cancer Center, Unit III, Peking University Cancer Hospital between January 2019 and April 2021 were retrospectively analyzed. Inclusion criteria: (1) rectal adenocarcinoma confirmed by pathology; patient age of ≥ 18 years and ≤ 80 years; (2) the distance from low margin of tumor to anal verge ≤ 10 cm under sigmoidoscopy; (3) ECOG performance status score 0-1; (4) clinical stage T3c, T3d, T4a or T4b, or extramural venous invasion (EMVI) (+) or mrN2 (+) or mesorectal fasciae (MRF) (+) based on MRI; (5) no evidence of distant metastases; (6) no prior pelvic radiation therapy, no prior chemotherapy or surgery for rectal cancer; (7) no systemic infection requiring antibiotic treatment and no immune system disease. Exclusion criteria: (1) anticipated unresectable tumor after neoadjuvant treatment; (2) patients with a history of a prior malignancy within the past 5 years, or with a history of any arterial thrombotic event within the past 6 months; (3) patients received other types of antitumor or experimental therapy; (4) women who were pregnant or breast-feeding; (5) patients with any other concurrent medical or psychiatric condition or disease; (6) patients received immunotherapy (PD-1 antibody). The neoadjuvant therapy consisted of three stages: PD-1 antibody (sintilimab 200 mg, IV, Q3W) combined with CapeOx regimen for three cycles; long-course intensity modulated radiation therapy (IMRT) with gross tumor volume (GTV) 50.6 Gy/CTV 41.8 Gy/22f; CapeOx regimen for two cycles after radiotherapy. After oncological evaluation following the end of the third stage of treatment, surgery or watch and wait would be carried out. Surgical safety, histopathological changes and short-term oncological outcome were analyzed. Results: There were 15 males and 9 females with a median age of 65 (47-78) years. Median distance from the lower margin of the tumor to the anal verge was 4 (3-7) cm. The median maximal diameter of the tumor was 5.1 (2.1-7.5) cm. Twenty patients were cT3, 4 were cT4, 8 were cN1, 5 were cN2a, 11 were cN2b. Ten cases were MRF (+) and 10 were EMVI (+). All the patients were mismatch repair proficient (pMMR). During the neoadjuvant treatment period, 6 patients (25.0%) developed grade 1-2 treatment-related adverse events, including 3 immune-related adverse events. As of April 30, 2021, 20 patients (83.3%, 20/24) had received surgical resection, including 19 R0 resections and 16 sphincter-preservation operations. Morbidity of postoperative complication was 25.0% (5/20), including 2 cases of Clavien-Dindo grade II (1 of anastomotic bleeding and 1 of pseudomembranous enteritis), 3 cases of grade I anastomotic stenosis. Pathological complete response (pCR) rate was 30.0% (6/20) and major pathological response rate was 20.0% (4/20). None of Ras/Raf mutants had pCR or cCR (0/5), while 6 of 17 Ras/Raf wild-type patients had pCR and 3 had cCR, which was significantly higher than that of Ras/Raf mutants (P<0.01). Nine of 16 patients with Ras/Raf wild-type and differentiated adenocarcinoma had pCR or cCR. Among other 4 patients without surgery, 3 patients preferred watch and wait strategy because their tumors were assessed as clinical complete response (cCR), while another one patient refused surgery as the tumor remained stable. After a median follow-up of 11 (6-24) months, only 1 patient with signet ring cell carcinoma had recurrence. Conclusions: PD-1 antibody combined with total neoadjuvant chemoradiotherapy in the treatment of locally advanced rectal cancer has quite good safety and histopathological regression results. Combination of histology and genetic testing is helpful to screen potential beneficiaries.
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Antineoplastic Combined Chemotherapy Protocols , Apoptosis , Chemoradiotherapy , Neoadjuvant Therapy , Neoplasm Recurrence, Local , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Rectal Neoplasms/therapy , Retrospective Studies , Risk Factors , Treatment OutcomeSubject(s)
Animals , Humans , Mice , Angiotensin II , Hypertension/chemically induced , Mice, Inbred C57BL , Muscle, Smooth, Vascular , Myocytes, Smooth MuscleABSTRACT
Arachidonic acid (AA) is an ω-6 polyunsaturated fatty acid, which mainly exists in the cell membrane in the form of phospholipid. Three major enzymatic pathways including the cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 monooxygenase (CYP450) pathways are involved in AA metabolism leading to the generation of a variety of lipid mediators such as prostaglandins, leukotrienes, hydroxyeicosatetraenoic acids (HETEs) and epoxyeicoastrienoic acids (EETs). These bioactive AA metabolites play an important role in the regulation of many physiological processes including the maintenance of liver glucose and lipid homeostasis. As the central metabolic organ, the liver is essential in metabolism of carbohydrates, lipids and proteins, and its dysfunction is associated with the pathogenesis of many metabolic diseases such as type 2 diabetes mellitus, dyslipidemia and nonalcoholic fatty liver disease (NAFLD). This article aims to provide an overview of the enzymatic pathways of AA and discuss the role of AA-derived lipid mediators in the regulation of hepatic glucose and lipid metabolism and their associations with the pathogenesis of major metabolic disorders.
Subject(s)
Humans , Arachidonic Acid/metabolism , Diabetes Mellitus, Type 2 , Glucose/metabolism , Homeostasis , Lipid Metabolism , LiverABSTRACT
Prostaglandin E2 (PGE2), a bioactive lipid mediator, is one of the most important locally acting factors involved in a variety of physiological and pathophysiological processes. PGE2 binds with four EP receptors (EP1-4) to activate G protein-coupled receptor signaling responses. Recent functional and molecular studies have revealed that PGE2 plays an essential role in regulation of renal fluid transport via a variety of mechanisms. The water balance mainly depends on the regulation of aquaporin-2 (AQP2) by arginine vasopressin (AVP) in renal collecting duct principal cells. In recent years, increasing evidence suggests that PGE2 plays an important role in renal water reabsorption in the collecting ducts. In this paper, we reviewed the role of PGE2 and its receptors in the regulation of water reabsorption in the kidney, which may provide a new therapeutic strategy for many diseases especially nephrogenic diabetes insipidus.
Subject(s)
Humans , Aquaporin 2/metabolism , Biological Transport , Diabetes Insipidus, Nephrogenic , Dinoprostone , Water/metabolismABSTRACT
Objective:A systematical study on the anti-breast cancer mechanism of tryptanthrin in breast cancer-bearing mice was done by Label-free proteomics. Method:UPLC-MS was used to detect the expressed-proteins of tryptanthrin inhibiting breast cancer in mice, chromatographic separation was achieved on the Ionoptics nano UPLC C18 column (0.075 mm×250 mm, 1.6 μm), and gradient elution was performed with 0.1% formic acid aqueous solution-0.1% formic acid acetonitrile solution as mobile phase. Data acquisition was carried out in electrospray ionization (ESI) under the positive ion mode, the scanning range was m/z 100-1 700, MaxQuant 1.6.5.0 was used for database retrieval. Label-free proteomics with high resolution mass spectrometry was used to screen differentially expressed proteins between the model group of 4T1 breast cancer mice and oral administration group of tryptanthrin (100 mg·kg-1). The proteomics of tryptanthrin against breast cancer was carried out. Result:A total of 3 997 proteins were identified in this proteomics research, and 2 911 proteins were quantifiable. A total of 750 differentially expressed proteins were identified between the model group and the tryptanthrin group, 286 proteins were up-regulated and 464 proteins were down-regulated. Gene ontology analysis showed that these differentially expressed proteins were mainly involved in biological processes of proliferation, cell migration, apoptosis, immunity, angiogenesis, inflammatory regulation, etc. Kyoto encyclopedia of genes and genomes pathway analysis further indicated that these proteins were mainly concentrated in T cell receptors, B cell receptors, Toll-like receptors, nuclear transcription factor-κB (NF-κB), Ras proteins, interleukin-17, tumor necrosis factor, phosphatidylinositol 3-kinase/protein kinase B (PI3K-Akt), mitogen-activated protein kinase (MAPK) and other signaling pathways. Conclusion:The differentially expressed proteins closely related to anti-breast cancer effect of tryptanthrin on 4T1 breast cancer mice are effectively screened out, including up-regulating proteins of leukocyte differentiation antigen 14 (CD14), prostaglandin G/H synthase 2 (PTGS2), E3 ubiquitin-protein ligase and down-regulating proteins of CD44, heat shock 70 kDa protein 1A (HSPA1A), macrophage migration inhibitory factor (MIF), NF-κB, ribosomal protein S6 kinase alpha-4 (RPS6KA4) and high mobility group protein B1 (HMGB1). These findings suggest that tryptanthrin can inhibit breast cancer in mice mainly through regulating tumor inflammatory microenvironment.
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Objective To provide reliable indicators for effective prevention and control of COVID-19, we examined the biochemical indicators as well as anti-SARS-CoV-2 IgM and IgG antibodies in confirmed and suspected COVID-19 patients. Methods A total of 56 confirmed and suspected COVID-19 cases quarantined during January-March, 2020 in Gansu Provincial People′s Hospital and People′s Hospital of Xigu District, Gansu Province were included.Based on the results of nucleic acid testing and CT scan finding, they were divided into three groups: positive in both nucleic acid testing and CT scan finding; positive in nucleic acid testing but negative in CT scan finding; negative in both nucleic acid testing and CT scan finding.COVID-19 viral nucleic acid was detected and chest CT scan was performed.The following biochemical indicators were examined: total protein, albumin, total bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyltranspeptidase, creatine kinase and lactate dehydrogenase.SPSS 22.0 statistical software was used to analyze the differences in the biochemical indicators among these three groups, as well as the temporal trend of IgM and IgG antibodies at different points of time. Results There were significant differences in the mean values of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase between these three groups (P < 0.05), whereas no significant difference in the mean value of total protein and albumin (P>0.05).ROC curve indicated that aspartate aminotransferase had the largest maximum area under the curve (AUC, 0.834), whereas alanine aminotransferase had the highest sensitivity (1.0) and total bilirubin had the highest specificity (0.927).Thus, aspartate transaminase provided the best prediction for the diagnosis of COVID-19, with sensitivity of 0.786, specificity of 0.854, and the maximum AUC of 0.834.In 12 of 16 confirmed COVID-19 patients tested IgG positive after 10 days of diagnosis, and 10 of 10 confirmed COVID-19 patients tested IgG positive after 14 days of diagnosis. Conclusion Aspartate aminotransferase may be the most useful indicator in the diagnosis of COVID-19.
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OBJECTIVE@#To investigate the expression level of miR-181b in CD19+ B lymphocytes of patients with chronic lymphocytic leukemia (CLL), to analyze the relationship between its expression and the prognosis of CLL patients, and to predict the potential target gene of miR-181b in CLL by using bioinformatics.@*METHODS@#Eight-four patients with CLL treated in People's Hospital of Xinjiang Uygur Autonomous Region from June 2013 to June 2018 were selected. and 20 healthy people were selected as control group. RNA was extracted from CD19+B lymphocytes of peripheral blood by magnetic bead sorting, the expression level of miR-181b was detected, and it's expression differences in different IPI groups were analyzed. The correlation between the expression level of miR-181b and PFS of CLL patients also was analyzed. miR-181b target genes were predicted by online database and literatures, and gene annotation analysis and relevant signal pathway analysis were performed for candidate target genes.@*RESULTS@#The expression level of miR-181b in CLL patients was significantly lower than that in control group (P<0.01); The expression level of miR-181b in the low-risk group was higher than that in high-risk group and extremely high-risk group (P<0.05), but there was no statistical difference between low-risk group and medium-risk group (P=1.00). The expression level of miR-181b in medium-risk group was higher than that in high-risk group and extremely high-risk group (P<0.05), but there was no difference between high-risk group and extremely high-risk group (P=1.00). ROC curve results showed that the area under the curve (AUC) was 0.792 (P<0.01).When the expression level of miR-181b was at the threshold value of 0.279, it showed a better sensitivity (62.9%) and specificity (91.8%). Survival analysis results suggested that compared with the high expression group, the miR-181b low expression group had poor PFS (log rank: P=0.047). Prediction of miR-181b by using the starBase, targetscan and picTar database and its combination with literature reports indicated that CARD11, ZFP36L1, RUNX1, NR4A3, ATP1B1, PUM1 and PLAG1 related with blood diseases, and up-regulated CARD11 and ZFP36L1 participated in lymphoid tumor formation by promoting cell proliferation and inhibiting cell aging.@*CONCLUSION@#The expression level of miR-181b in CLL group are significantly lower than that in the controls group, and the low expression of miR-181b relates with poor prognosis of CLL patients. Through bioinformatics prediction and combined with literature reports, it is speculated that CARD11 and ZFP36L1 as target genes of miR-181b may be participated in the occurrence and development of CLL. Further experiments are needed to verify this result.
Subject(s)
Humans , Apoptosis Regulatory Proteins , Cell Proliferation , Leukemia, Lymphocytic, Chronic, B-Cell , Genetics , MicroRNAs , PrognosisABSTRACT
Objective To investigate the safety and effectiveness of bilateral transverse thoracic muscle plane (TTP) block (modified approach) combined with general anesthesia in off-pump coronary artery bypass grafting (OPCABG). Methods The clinical data of 60 patients undergoing OPCABG, selected from March to August 2019 in General Hospital of Northern Theater Command, were retrospectively analyzed and divided into TTP block with general anesthesia group (TTP+general anesthesia group, n=30) and general anesthesia group (n=30) according to anesthesia mode. Patients in TTP+general anesthesia group undergone bilateral TTP block (modified approach, 0.25% ropivacaine 20 ml each side) before anesthesia induction, and both groups were induced by routine anesthesia. The mean arterial pressure (MAP) and heart rate (HR) were recorded and analyzed before and after cutting, splitting and closing the sternum, and the total dosage of sufentanil at the end of operation was recorded. The levels of lactic acid and blood glucose in blood gas analysis of patients at the time they entered the room, the operation ended and at 2, 4, 6, 8, 10, 12, 16, 20 and 24 h after the operation were recorded. The visual analogue scale (VAS) scores in resting and moving state at 12, 24 and 48 h after operation were recorded. The numbers of patients who were first added analgesic drugs (pethidine) on the day, the first day and the second day after operations were recorded, and the occurrence of postoperative adverse reactions was recorded. Results Compared with general anesthesia group, the change rate of MAP and HR in TTP+general anesthesia group decreased slightly at each time point, but the difference was not statistically significant (P>0.05). The differences of lactic acid at 2 and 4 h after operation were statistically significant (P0.05); while the dosage of sufentanil in TTP+general anesthesia group was obviously decreased, and the number of patients who were added analgesics at the postoperative day was markedly reduced, both were with statistical significance (P0.05). The incidence of postoperative chills was obviously lower in TTP+general anesthesia group than in general anesthesia group with a statistical difference (P<0.05). Conclusion Bilateral TTP block (modified approach) combined with general anesthesia can provide good perioperative analgesia for patient undergoing OPCABG, reduce the use of opioids, and inhibit the stress response to a certain extent, thus having better safety and effectiveness.
ABSTRACT
OBJECTIVE@#To investigate the effects and molecular mechanisms of 2-12alkyl-6-methoxycyclohexa-2,5-diene-1,4-dione(DMDD) on diffuse large B lymphoma (DLBCL).@*METHODS@#In animal experiments, 4-week-aged BALB/C mice were divided into 5 groups, 20 mice in each group. Mice were inguinal injected with DLBCL cell line OCI-LY19 cells 0.1 ml at the concention of 1 × 10 /ml. Two days later, mice were treated with DMDD at the doses of 0, 1, 5, 25 and 125 mg/kg by intragastric administration respectively, once /2 days. Ten mice of each group were killed on the 18th day of administration, and the tumor tissues were weighed. The survival time of the remaining mice were recorded. In cell experiments, OCI-LY19 cells were added to 96-well culture plates, 100 μl 1×10 cells/ml per well, then 100 μl DMDD was added to the well and the final concentrations were 0, 1, 5, 25 and 125 μmol/L respectively. The cells were treated with DMDD for 0, 24, 48 and 72 h, three wells in each group. The cell proliferation activity was detected by MTS assay. According to the results of cell proliferation experiments, OCI-LY19 cells were treated with DMDD at the concentrations of 0 μmol/L, 5 μmol/L and 25 μmol/L for 24 h. The apoptosis rate was analyzed by flow cytometry, the nuclear type was observed by hoechst staining, the mitochondrial membrane potential was observed by JC-1 staining, cytotoxicity of drugs was evaluated by LDH release experiment, gene expression and transcription were analyzed by qPCR and Western blot.@*RESULTS@#Compared with 0 mg/kg drug group, DMDD at the dose of 1~125 mg/kg could inhibit the growth of tumor tissue in mice and prolong their survival time (P<0.01). Cell experiments showed: in DMDD group, the proliferation activity of OCI-LY19 cells was decreased significantly and the level of apoptosis was increased significantly (P<0.01), nuclear fragmentation, agglutination, apoptotic bodies occurred and mitochondrial membrane potential was decreased, the LDH release rate was increased significantly (P<0.01), the expressions of caspase-3 and bax genes and the phosphorylation level of Ikappa B alpha in cells were up-regulated significantly, the protein expression levels of bcl-2, bcl-xL, jak2 and stat3 were inhibited significantly (P<0.01).@*CONCLUSION@#DMDD can inhibit the expressions of JAK2, STAT3 and p-Ikappa B alpha in JAK2/STAT3 and NF-kappa B signal pathways, down-regulate BCL-2/BAX and activate Caspase-3, finally, activate the endogenous pathway of mitochondrial apoptosis in OCI-LY19 cells and promote the apoptosis of DLBCL cells, inhibit proliferation of OCI-LY19 cells. It has inhibitive effects on DLBCL.
Subject(s)
Animals , Mice , Apoptosis , Cell Line, Tumor , Cell Proliferation , Cyclohexenes , Pharmacology , Lymphoma, Large B-Cell, Diffuse , Drug Therapy , Pathology , Mice, Inbred BALB C , Signal TransductionABSTRACT
OBJECTIVE@#The aim of this study was to determine whether low calf circumference (CC) could predict nutritional risk and the cutoff values of CC for predicting nutritional risk in hospitalized patients aged ⪖ 80 years.@*METHODS@#A total of 1,234 consecutive patients aged ⪖ 80 years were enrolled in this study. On admission, demographic data, CC, and laboratory parameters were obtained. Patients with Nutritional Risk Screening 2002 (NRS-2002) total score ⪖ 3 were considered as having nutritional risk.@*RESULTS@#CC values were significantly lower in patients with nutritional risk compared to those in patients without nutritional risk [27.00 (24.50-31.00) vs. 31.00 (29.00-33.50], P < 0.001]. CC was negatively correlated with age and nutritional risk scores. Logistic regression analysis of nutritional risk revealed that body mass index, albumin level, hemoglobin level, cerebral infarction, neoplasms, and CC (OR, 0.897; 95% confidence interval, 0.856-0.941; P < 0.001) were independent impact factors of nutritional risk. Nutritional risk scores increased with a decrease in CC. In men, the best CC cutoff value for predicting nutritional risk according to the NRS-2002 was 29.75 cm. In women, the cutoff value was 28.25 cm.@*CONCLUSION@#CC is a simple, noninvasive, and valid anthropometric measure to predict nutritional risk for hospitalized patients aged ⪖ 80 years.
Subject(s)
Aged, 80 and over , Female , Humans , Male , Anthropometry , Methods , China , Hospitalization , Leg , Nutritional Status , Risk Assessment , MethodsABSTRACT
Adipose tissue is the energy storage organ of the body, and excess energy is stored in adipocytes in the form of lipid droplets. The homeostasis of adipose tissue is the basis for the body to maintain normal metabolic activity. Prostaglandin E (PGE) is an important lipid mediator in the body. It is synthesized in almost all tissues and participates in the regulation of many physiological processes such as blood pressure, glucose and lipid metabolism, and inflammation. PGE is abundant in white adipose tissue, where it is involved in the regulation of fat metabolism. PGE plays its biological role through binding to four G protein coupled receptors (prostaglandin E receptors), including EP-1, -2, -3, and -4. The EP4 subtype has been proved to play an important role in adipogenesis and adipose metabolism: it could inhibit adipogenesis while it was activated, whereas its knockout could promote lipolysis. This review summarized the relationship between EP4 and adipose metabolism, hoping to identify new targets of drug development for metabolic disorders.
Subject(s)
Humans , Adipocytes , Adipogenesis , Adipose Tissue , Metabolism , Receptors, Prostaglandin E, EP4 Subtype , PhysiologyABSTRACT
Prostaglandin E2 (PGE2) is a cyclooxygenase metabolite of arachidonic acid. It acts as a bioactive lipid and plays an important role in regulating many biological processes. PGE2 binds to 4 different G protein-coupled receptors including prostaglandin E2 receptor subtypes EP1, EP2, EP3 and EP4. The EP4 receptor is widely expressed in most of human organs and tissues. Increasing evidence demonstrates that EP4 is essential for cardiovascular homeostasis and participates in the pathogenesis of many cardiovascular diseases. Here we summarize the role of EP4 in the regulation of cardiovascular function and discuss potential mechanisms by which EP4 is involved in the development of cardiovascular disorders with a focus on its effect on inflammation.