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Objective The potential mechanism of hepatotoxicity induced by rhubarb was preliminarily explored by network pharmacology and verified by cell experiments.Methods Based on network pharmacology,component collection and target prediction are carried out through multiple databases.PPI network construction,GO enrichment analysis and KEGG pathway analysis were combined with software to systematically predict the mechanism of hepatotoxicity induced by rhubarb.The pathway information predicted by network pharmacology was verified by primary hepatocyte experiments and Western blot experiments.Results The results of network pharmacology showed that RH was the main component of hepatotoxicity induced by rhubarb.Seventeen core targets of hepatotoxicity induced by rhubarb were obtained.KEGG results suggested that DNA damage and apoptosis were one of the key mechanisms of hepatotoxicity induced by rhubarb.The results of primary hepatocytes and Western blot showed that RH could inhibit the viability of primary hepatocytes in a time-dose dependent manner.ABT and SFP can significantly reduce the toxicity of RH on primary liver cells in mice,and RFP can increase the toxicity of RH to mouse primary liver cells.Upregulation of γ-H2AX and PARP-1 protein in primary liver cells of mice after treatment with different concentrations of RH.Conclusion RH in rhubarb can significantly inhibit the viability of mouse primary hepatocytes,and its toxicity to mouse primary hepatocytes is mainly caused by the metabolic activation of RH by CYP 2C9.RH can activate PARP-1 protein,phosphorylate H2AX,induce DNA damage and apoptosis in mouse primary hepatocytes.
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Objective To analyse the differential metabolites and related metabolic pathways in stable angina pectoris of coronary artery heart disease with spleen deficiency and phlegm turbidity syndrome by serum metabolomics.Methods This study observed 60 patients with stable angina pectoris of coronary artery heart disease with spleen deficiency and phlegm turbidity syndrome and 60 healthy volunteers in the same period.Liquid chromatography-mass spectrometry(LC-MS)was performed on the serum metabonomics.The differential metabolites were identified by multivariate statistical analysis of the original spectrogram and original data,and enrichment analysis of KEGG metabolic pathway was analyzed.Results A total of 60 patients in the group of stable angina pectoris of coronary artery heart disease with spleen deficiency and phlegm turbidity syndrome participated in the study,and a total of 60 healthy volunteers in the control group participated in the study.There was no statistical difference in general information and biochemical indicators between the two groups(P>0.05);Eighteen differential metabolites were found respectively,including phenylacetaldehyde,orthophosphate,guanosine,diethyl phosphate,2-dehydro-d-gluconate,guanine and 5-(2-hydroxyethyl)-4-methylthiazole down-regulated expression,taurocholate,2-propylglutaric acid,8-amino-7-oxononanoate,l-tyrosine,s-sulfo-l-cysteine,cyclohexanecarboxylic acid,porphobilinogen,(r)-acetoin,octanoylglucuronide,melatonin and solanine up-regulated expression,involving phenylalanine metabolism,thiamine metabolism,purine metabolism.Conclusion The differential metabolites reveal the metabolic essence of stable angina pectoris of coronary artery heart disease with spleen deficiency and phlegm turbidity syndrome from the micro level,and can provide clues for clinical early warning of patients with stable angina pectoris of coronary artery heart disease with spleen deficiency and phlegm turbidity syndromet.
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Objective:To explore the feasibility of cardiac T 2 weighted dark blood sequence (T 2W-DB) based on artificial intelligence assisted compression-sensing(ACS) in clinical cardiac MR examination, compared with the conventional cardiac fast spin-echo T 2W-DB sequence. Methods:A total of 38 patients referred for cardiac MR examination in Tongji Hospital were enrolled prospectively from August to December 2021. The conventional T 2W-DB scan and the single-shot ACS T 2W-DB scan were acquired at continuous short-axial slices covering the whole left ventricle in all patients, and the acquisition time of each scan was recorded. The image quality of the two sequences was evaluated by the objective quantitative parameters and the subjective scoring methods, respectively. The signal to noise ratio (SNR), the contrast to noise ratio of the interventricular septum to blood pool (CNR), and the sharpness of the images were calculated. The subjective scoring was to evaluate the overall image quality, the effect of blood pool suppression, the visibility of right ventricular free wall, left ventricular free wall, and interventricular septum with a 5-point Likert scale. The intraclass correlation coefficient and Kendall W were calculated to evaluate the interobserver agreement of the objective quantitative parameters and subjective scoring. The paired t-test or Wilcoxon test was used to compare the difference in acquisition time, objective quantitative parameters and subjective scoring between the conventional T 2W-DB and the single-shot ACS T 2W-DB. Results:The inter-observer agreement between the single-shot ACS T 2W-DB and conventional T 2W-DB was good in all the objective quantitative parameters and subjective scoring of image quality ( P<0.05 for all). Compared with conventional T 2W-DB, acquisition time of single-shot ACS T 2W-DB was remarkably shortened [(85.8±14.7) s vs. (16.9±3.0) s, t=35.42, P<0.001]. Compared with SNR (66.4±29.0) and CNR(61.8±28.6) of conventional T 2W-DB, single-shot ACS T 2W-DB had significantly higher SNR(110.8±36.8, t=-8.13, P?0.001) and CNR(88.2±31.1, t=-5.89, P?0.001). Compared with conventional T 2W-DB, single-shot ACS T 2W-DB had better blood pool inhibition effect (4.6±0.6 vs. 4.7±0.5, Z=-2.64, P=0.008). There was no significant difference in overall image quality, visibility of right ventricular free wall, left ventricular free wall, and interventricular septum between the two sequences( P>0.05 for all). Conclusions:In cardiac MR examination, compared with the conventional T 2W-DB sequence, the single-shot ACS T 2W-DB sequence can significantly shorten the acquisition time and obtain better image quality.
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ObjectiveTo reveal the targets and molecular mechanisms of the action of Qiangxin Decoction （强心汤） for the treatment of chronic heart failure based on the combination of network pharmacology and molecular docking. MethodsThe active ingredients of Qiangxin Decoction were retrieved from TCMSP database， and the targets of chronic heart failure were screened by searching GeneCards， OMIM， TTD， PharmGkb， and DrugBank databases， and the intersections were taken to obtain the intersecting targets of Qiangxin Decoction for the treatment of chronic heart failure. STRING platform was used to construct the protein-protein interaction network （PPI）， Cytoscape 3.8.0 software was used to calculate the network topology to screen the core targets， and R 4.2.3 was used to construct the “active ingredient-target” network by analyzing the GO enrichment analysis and KEGG pathway enrichment analysis. AutoDock 1.5.7 was used for molecular docking to predict the binding performance of active ingredients and core targets. ResultsSeventy-five intersecting targets were identified for the treatment of chronic heart failure with Qiangxin Decoction， among which the core targets were estrogen receptor 1 （ESR1， degree value=7）， nuclear receptor coactivator 1 （NCOA1， degree value=8）， glucocorticoid receptor （NR3C1， degree value=7）， and nuclear receptor coactivator 2 （NCOA2， degree value=7）. GO enrichment analysis showed that the top 3 items with the smallest P value in molecular function were G protein-coupled amine receptor activity， postsynaptic neurotransmitter receptor activity， and neurotransmitter receptor activity （P＜0.01）； the top 3 items with the smallest P value in biological process were adenylyl cyclase-activated adrenergic receptor signaling pathway， adrenergic receptor signaling pathway， and adenylyl cyclase-regulated G protein-coupled receptor signaling pathway （P＜0.01）； the top 3 items with the smallest P values in cellular composition were components of the postsynaptic membrane， synaptic membrane， and presynaptic membrane （P＜0.01）. KEGG enrichment analysis showed that the top 5 key signaling pathways were neuroactive ligand-receptor interactions， calcium signaling pathway， dopaminergic synapses， cocaine addiction， and cyclic guanosine monophosphate-protein kinase G （cGMP-PKG） signaling pathway. The molecular docking results showed that lignans and isoflavones had lower binding energies and more structural stability with the four core targets （ESR1， NCOA1， NR3C1， NCOA2）. ConclusionThe treatment of chronic heart failure by Qiangxin Decoction was associated with neuroactive ligand-receptor interactions， calcium signaling pathway， dopaminergic synapses， chemoattractant-receptor activation， cGMP-PKG signaling pathway， lipids and atherosclerosis， and cAMP signaling pathway， and lignans and isoflavones may be the core active compounds in its treatment of chronic heart failure.
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Autophagy is an intracellular degradation process that maintains cellular homeostasis. It is essential for protecting organisms from environmental stress. Autophagy can help the host to eliminate invading pathogens, including bacteria, viruses, fungi, and parasites. However, pathogens have evolved multiple strategies to interfere with autophagic signaling pathways or inhibit the fusion of autophagosomes with lysosomes to form autolysosomes. Moreover, host cell matrix degradation by different types of autophagy can be used for the proliferation and reproduction of pathogens. Thus, determining the roles and mechanisms of autophagy during pathogen infections will promote understanding of the mechanisms of pathogen‒host interactions and provide new strategies for the treatment of infectious diseases.
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Autophagy , Bacteria , Host-Pathogen Interactions , Lysosomes , Signal TransductionABSTRACT
Objective:To evaluate the independent prognostic value of minute ventilation/carbon dioxide production slope (VE/Vco 2 slope)on heart failure after acute myocardial infarction. Methods:131 patients with acute myocardial infarction (AMI) treated in the cardiology department of China-Japan Friendship Hospital from September 2018 to September 2019 were collected and followed up 3 months after discharge. They were divided into heart failure (HF) group and non-heart failure (NHF) group. All the patients underwent cardiopulmonary exercise test (CPET) before discharge.Results:Three months after discharge, the VE/Vco 2 slope was higher in HF group than in NHF group (36.7±3.8 vs 29.7±4.0, P=0.014). The best VE/Vco 2 slope cutoff for the prediction of heart failure after 3 month was 33.05 with a sensitivity of 81.4% and a specificity of 80.6% [area under curve (AUC) was 0.844, P<0.001]. VE /Vco 2 slope level was an independent predictor of heart failure in patients with acute myocardial infarction after discharge ( OR=1.245, 95% CI: 1.021-1.366, P=0.019). Other independent indicators related to heart failure included N-terminal pro-B type natriuretic peptid (NT-proBNP) level ( OR=1.283, 95% CI: 1.019-1.399, P=0.033). Conclusions:VE/Vco 2 slope yielded strong, independent predictive value for heart failure at 3 month after discharge to AMI patients.
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Ferroptosis, as a newly discovered cell death form, has become an attractive target for precision cancer therapy. Several ferroptosis therapy strategies based on nanotechnology have been reported by either increasing intracellular iron levels or by inhibition of glutathione (GSH)-dependent lipid hydroperoxidase glutathione peroxidase 4 (GPX4). However, the strategy by simultaneous iron delivery and GPX4 inhibition has rarely been reported. Herein, novel tumor microenvironments (TME)-activated metal-organic frameworks involving Fe & Cu ions bridged by disulfide bonds with PEGylation (FCSP MOFs) were developed, which would be degraded specifically under the redox TME, simultaneously achieving GSH-depletion induced GPX4 inactivation and releasing Fe ions to produce ROS
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Cerebral small vessel disease refers to a series of clinical, imaging and pathological syndromes caused by various diseases affecting small arteries, arterioles, capillaries, venules, and venules in the brain, thereby causing ischemia or hemorrhage in brain tissue. At present, intravenous thrombolytic therapy is the first choice for the treatment of acute ischemic stroke, however a large number of studies have shown that the presence of cerebral small vessel disease before acute ischemic stroke increases the risk of intravenous thrombolysis. In this article, the recent research progresses about the relationship between cerebral small vessel disease and hemorrhagic transformation after venous thrombolysis in acute ischemic stroke are reviewed, aiming to provide a new reference for clinical intravenous thrombolytic therapy.
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Cerebral small vessel disease refers to a series of clinical, imaging and pathological syndromes caused by various diseases affecting small arteries, arterioles, capillaries, venules, and venules in the brain, thereby causing ischemia or hemorrhage in brain tissue. At present, intravenous thrombolytic therapy is the first choice for the treatment of acute ischemic stroke, however a large number of studies have shown that the presence of cerebral small vessel disease before acute ischemic stroke increases the risk of intravenous thrombolysis. In this article, the recent research progresses about the relationship between cerebral small vessel disease and hemorrhagic transformation after venous thrombolysis in acute ischemic stroke are reviewed, aiming to provide a new reference for clinical intravenous thrombolytic therapy.
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Objective To prepare dual-targeted pH-sensitive DOX prodrug-microbubble complex and explore the characterization of complex with ultrasound as well as drug release in vitro . Methods Dual-targeted ligands ,cRGD and folate were conjugated with heparin using carbodiimide method ,and then the dual-targeted pH-sensitive DOX prodrug was synthesized by coupling DOX via a pH-sensitive hydrazone bond . The prodrug was combined with microbubbles to prepare complex by biotin-avidin system . The characterization of complex with/without ultrasound was investigated for size ,morphology and drug loaded capacity .In vitro drug release manner of complex with/without at different pH was analyzed . Results DOX content of the prodrug determined by UV Spectrophotometry was about 18 .9％ . Dynamic laser light scattering analysis( DLS) ,corresponding to transmission electron microscope( TEM ) findings ,revealed its inhomogeneous size distribution [ mean size ( 159 .7 ± 24 .5) nm and ( 1089 .0 ± 174 .9) nm ] . However ,the complex was dispersed into uniform fragment after ultrasound irradiation [ mean size ( 155 .9 ± 29 .8) nm , polymer dispersity index( PDI) 0 .22 ,Zeta potential - ( 20 .6 ± 3 .4) mV ] . The cumulative release rate of DOX from both complex and complex with ultrasound at pH 5 .0 were much faster than that at pH 7 .4 , displaying a pH-triggered release manner . Conclusions Dual-targeted pH-sensitive DOX prodrug-microbubble complex displays excellent drug release activity in acid environment . Uniform fragment and smaller particle size of complex could be achieved via ultrasound irradiation ,promoting DOX accumulation within tumor tissue and facilitating in vivo antitumor ability .
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Primary central nervous system lymphoma (PCNSL) is a rare,extranodal form of non-Hodgkin lymphoma that is confined to the central nervous system.It mainly involves the deep brain white matter,the lateral ventricle and the corpus callosum.A decline in cognitive function and headache are the typical clinical manifestations of the disease.We report a patient with PCNSL in bilateral middle cerebellar peduncles,whose clinical manifestations were only dizziness and unstable walking.Brain MRI manifestations were not typical in early time,with symmetrical hypointensity lesions on T1-weighted imaging,hyperintensity lesions on T2-weighted imaging,and edema zone around on FLAIR imaging.Enhanced scan showed marginal contrast enhancement,but no significant occupying effect.These changes were similar to the multiple characteristics of multiple sclerosis.The history of autoimmune diseases and cerebrospinal fluid examination highly indicated demyelinating disease.The differences of clinical manifestations,MRI characteristics,diagnosis,treatment and prognosis between PCNSL in bilateral middle cerebellar peduncles and multiple sclerosis were analyzed to imorove the understanding of the disease in clinical practice.
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Objective To analyze the technology competition situation in vaccine industry of Jilin Province from the visual angle of patents. Methods The Dawei Patents Database-covered patents data of vaccine industry in Jilin Province were analyzed by patent mapping, patent metrical analysis and social network analysis respectively. Re-sults The vaccine industry in Jilin Province was in a growing stage with a good development situation and a solid strength in its research institutions. Conclusion Stress should be laid on city development-driven production, pro-duction-driven city development, and optimizing industry policies for the development of vaccine industry in Jilin Province. Scientific research institutions should strengthen their collaboration in professionals, technologies, funds and markets in order to make breakthroughs in technologies and realize the economic value of patents.
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Objective To compare the effect of anesthesia management between enhanced recovery after surgery (ERAS) protocol and traditional protocol on stress level of thyroid surgery.Methods Sixty-two patients receiving thyroid surgery from May 2016 to August 2016, 13 males and 49 females, aged 18-65 years, of ASA physical status Ⅰ or Ⅱ, were randomly divided into group ERAS (n=29) and traditional group (group C, n=33).Each group had its own anesthesia management protocol.Operation method, operation duration, the level of pain during emergence and on the first postoperative day, the occurrence rate of complications and the satisfaction evaluation of pain and nausea and vomiting after the operation day were recorded.C-reactive protein (CRP), serum cortisol, interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor (TNF-α) before and after the operation day were evaluated.Results The visual analogue scale (VAS) pain score in group ERAS was lower than that in group C during emergence [(0.42±0.83) points vs (0.95±1.16) points]and on the first postoperative day [(1.90±1.21) points vs (2.73±1.40) points] (P<0.05).Group ERAS was more satisfied with pain relief at first day after the surgery than that of group C (P<0.05).The level of CRP in group ERAS was lower than that in group C on the operative day and the first postoperative day (P<0.05).In group C, the level of CRP on the operative day and the first postoperative day were much higher than those before the surgery (P<0.05).The occurrence rate of complications between the two groups had no statistical difference.Conclusion The perioperative ERAS anesthesia management of thyroid surgery is safe and effective in pain management, patient satisfaction and accelerated recovery.
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OBJECTIVE:To observe the effects of Gegenqinlian colon positioning tablet(GGQLJC)on colon tissue PPAR-γ, NF-κB p65 protein expressions of model rabbits with damp-heat type ulcerative colitis(UC). METHODS:56 rabbits were random-ly divided into normal group(normal saline),model group(normal saline),sulfasalazine tablet(SASP)group(positive control, 0.300 g/kg),Gegenqinlian tablet (GGQL) group (0.225 g/kg) and GGQLJC high-dose,medium-dose,low-dose groups (1.036, 0.518,0.259 g/kg),8 in each group. Except for normal group,rabbits in other groups were cultured for damp-heat-type UC mod-el,intragastrically administrated in the second day of last administration,once a day,for 14 d. Disease activity index(DAI),co-lonic mucosal damage index (CMDI),histological damage (TDI) were scored;colon,spleen and thymus indexes were deter-mined;PPAR-γ,NF-κB p65 protein expressions in colon tissue were detected. RESULTS:Compared with normal group,DAI, CMDI,TDI scores and spleen index,colon index,NF-κB p65 protein level in colon tissue in model group were significantly in-creased(P<0.01);thymus index,PPAR-γprotein level in colon tissue were significantly reduced(P<0.01). Compared with mod-el group,above-mentioned indexes in each administration group were significantly improved (P<0.05 or P<0.01). Compared with GGQL group,DAI and TDI scores,spleen index,colon index,NF-κB p65 protein level in colon tissue in SASP group, GGQLJC high-dose,medium-dose groups were significantly decreased (P<0.05);PPAR-γ protein level in colon tissue in SASP group,GGQLJC high-dose,medium-dose groups were significantly increased (P<0.05 or P<0.01). CONCLUSIONS:GGQLJC has certain improvement effects on model rabbits with damp-heat type UC,which is superior to GGQL. The mechanism may be re-lated to increasing PPAR-γprotein level and decreasing NF-κB p65 protein level in colon tissue.
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Objective To explore the diagnostic and score value of ultrasound on hemophiliac arthropathy referring to MRI on the diagnosis and score of hemophiliac arthropathy Methods The ultrasound and MRI examinations were performed on 42 joints of 42 hemophilia patients 14 knees 14 ankles and 14 elbows The consistency of ultrasound and magnetic resonance imaging in the detection and score of joint diseases was compared Finally inter-and intra-observer agreement of ultrasound scoring system were tested Results The consistency of ultrasound and magnetic resonance imaging was excellent κ=0 763-0 896 P < 0 001 in the detection of early soft tissue lesions effusion or hemarthrosis synovial hypertrophy hemosiderin excellent κ=0 793 P <0 001 in the detection of cartilage loss poor κ=0 133 P = 0 132 in the detection of erosions and poor κ= 0 100 P = 0 137 in the detection of subchondral cysts The consistency of ultrasound and magnetic resonance imaging was good to excellentκ=0 684-0 833 P < 0 001 in the score of early soft tissue lesions effusion or hemarthrosis synovial hypertrophy and hemosiderin and poor to good κ=0 145 -0 635 P <0 001 in the score of advanced osteochondral lesions cartilage loss and bone erosions The inter-observer agreement was good to excellent κ=0 676-0 870 P <0 001 for early soft tissue lesions and moderate to excellent κ=0 421- 0 75 1 P < 0 001 for advanced osteochondral lesions The intra-observer agreement was good to excellent κ=0 705-0 885 P <0 001 for early soft tissue lesions and moderate to good κ=0 532 -0 732 P <0 001 for advanced osteochondral lesions Conclusions Ultrasound plays an important role in detecting early soft tissue changes effusion or hemarthrosis synovial hypertrophy hemosiderin and cartilage loss which helps follow-up and guide clinical treatment.
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Important papers representing the advances in AIDS vaccine research were retrieved from Web of Sci-ence using HistCite.The citation chronological chart was plotted by analyzing the relation between their citation fre-quency and cited frequency , and analyzing their citation sequences , which shows the development rules and histori-cal development path in AIDS vaccine research , and provides a certain reference value for the researchers in related fields at home and abroad.
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A knowledge amount assessment index system was constructed by quantifying the knowledge-sharing will-ingness of staff in enterprises through case analysis according to the network centrality index. The effect of different staff on knowledge-sharing in enterprises was analyzed by calculating the index weight using the yaahp6 . 0 software and analyzing the correlation between its two factors.
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<p><b>OBJECTIVE</b>To evaluate the down stream involvement of the bile duct in hepatolithiasis.</p><p><b>METHODS</b>Mechanical damage to bile duct epithelia and long standing cholangitis as result of hepatolithiasis play an important role in the carcinogenesis of bile duct epithelia and stricture of the intra- and extra-hepatic bile duct. Macromorphological and microscopic changes in bile duct mucosa of 100 consecutive patients with hepatolithiasis were investigated using intra- or post-operative cholangioscopy. Biopsy specimens of lesions obtained during cholangioscopy were studied with immunohistochemical staining and flow cytometry to determine proliferative activity and DNA content. Five cases of well-proven cholangiocarcinoma were simultaneously studied as controls.</p><p><b>RESULTS</b>Of the 100 patients, those with chronic cholangitis accounted for 86% (86/100), proliferative lesions 11% (11/100), adenomatous polyps 1% (1/100), and adenocarcinoma 2% (2/100). The obvious mucosal lesion associated with hepatolithiasis was located down-stream of the bile duct, predominantly in the hilar region, e.g. orifices of the right/left hepatic duct and common hepatic duct (73% mucosa lesions in the hilar region). The intensity of cancer embryonic antigen stain and the proliferative cell nuclear antigen index increased with the development of bile duct lesions. Aneuploid DNA presented mainly in the high degree malignant adenocarcinomas (> 80% of cases).</p><p><b>CONCLUSIONS</b>The obvious mucosal lesions associated with hepatolithiasis were located down-stream of the bile duct, predominantly in the hilar region (73% of mucosal lesions). The proliferative activity of examined bile duct mucosa lesions increased with the development of pathological deterioration, which may contribute to the development of hilar bile duct stricture and hilar cholangiocarcinoma.</p>
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Adult , Aged , Humans , Middle Aged , Bile Ducts , Pathology , Carcinoembryonic Antigen , Cholangiocarcinoma , Lithiasis , Pathology , Liver Diseases , Pathology , Proliferating Cell Nuclear AntigenABSTRACT
Purpose To investigate the significance of tumor suppressor gene p15 and p16 expression in soft tissue leiomyosarcoma(LMS) and leiomyoma(LM). Methods Expressions of p15 and p16 was studied in 38 cases of LMS and 20 LM with immunohistochemical method. Results The abnormal expression rates of p15 and p16 in LMS were 18.4% and 42.1% respectively, and were significantly different. p15 abnormal expression rate in LM was 60%, significantly higher than in LMS. The total abnormal expression rate of p15 and p16 was 52.6% in LMS studied. Grade Ⅰ tumor had the significantly higher abnormal expression rate than that of grade Ⅱ or Ⅲ tumor. Fifteen cases of LMS were followed. The abnormal expression rate of p15 and p16 in recurrent group was 75%, significantly higher than that in non recurrent group. Conclusions Loss of expression of p16 protein is more frequent in LMS than that of p15, whereas deletion of p15 protein is more frequent in LM than in LMS. Loss of functions of p15 together with p16 participates in the tumorigenesis and progression of LMS, and is correlated with pathologic grading and prognosis of LMS.