1.Portal vein thrombosis in liver cirrhosis: Risk factors and protection strategies
Wenjuan FENG ; Ning ZHOU ; Yulu WANG ; Zhaoqin BAI
Journal of Clinical Hepatology 2024;40(1):169-174
Portal vein thrombosis (PVT) is one of the common complications during the natural course of liver cirrhosis and has an important influence on the progression of liver cirrhosis. This article mainly summarizes the research advances in the risk factors for PVT. There are many risk factors for PVT, and Virchow’s triad, namely venous stasis, hypercoagulability, and vascular endothelial injury and systemic inflammation caused by surgery or trauma, are considered the main reasons for the development and progression of PVT. At present, more prospective studies are still needed to validate the predictive models for the risk of PVT that have certain application prospects in clinical practice. Cirrhotic patients with PVT tend to have a poor prognosis, and complete obstructive PVT is associated with increased mortality after liver transplantation. Recent studies have shown that prophylactic anticoagulant therapy is safe and effective in patients with liver cirrhosis and can thus help with the prevention and treatment of PVT.
2.Exploring the Mechanism of Baihe Dihuang Decoction in the Treatment of Alzheimer's Disease Based on Network Pharmacology, Molecular Docking and Animal Experiment
Ru JIA ; Xiaoru ZHOU ; Yan CHEN ; Shuling ZHANG ; Zhaokai LAI ; Yulu WANG
Chinese Journal of Modern Applied Pharmacy 2024;41(8):1027-1037
OBJECTIVE
To explore the mechanism of Baihe Dihuang decoction in the treatment of Alzheimer's disease(AD) based on network pharmacology, molecular docking and animal experiment.
METHODS
TCMSP were used to predict the active components and targets of Baihe Dihuang decoction and disease-related targets were collected from GeneCards, OMIM and DRUGBANK databases, respectively. Target protein interactions were analyzed with STRING database and biological function and pathway were analyzed with Metascape database. Lastly relevant results were analyzed with Cytoscape 3.8.0. AutoDock vina software was used for molecular docking to analyze the binding energy of the active components and key targets of Baihe Dihuang decoction. PyMOL software were used to visualize the optimal docking results. ICR male mice were randomly divided into control group, model group, Rolipram group, low, medium and high dose group of Baihe Dihuang decoction. After 14 days of administration, the neurobehavioral scores of mice in each group were collected, and the expression of related proteins in brain tissue was detected, ELISA and Western blotting were used to detect the expression of the key protein cAMP, PKA, p-CREB and BDNF. At last, the adverse reaction of Baihe Dihuang decoction was observed by vomiting experiment.
RESULTS
A total of 13 active components and 39 key targets were collected from network pharmacology. The docking results showed that the first 10 core targets all performed well and their effects were closely related to PRKACA. Compared with the control group, the model group mice's recognition rate of new objects and the spontaneous alternation reaction rate were significantly reduced, the escape latency was significantly prolonged, and the target quadrant stay time, the number of crossing platforms were significantly reduced; cAMP, PKA, p-CREB and BDNF in the hippocampus of mice was significantly decreased. Baihe Dihuang decoction could reverse the behavior of AD mice and the expression of cAMP, PKA, p-CREB and BDNF. In the vomiting experiment, the anesthesia recovery time of the Rolipram group was significantly prolonged, while that of the Baihe Dihuang decoction group was not significantly affected.
CONCLUSION
The mechanism of Baihe Dihuang decoction in the treatment of AD may be related to its influence on cAMP-PKA and regulation of cAMP-PKA-CREB-BDNF signal pathway, and the adverse reactions are milder than those of clopramide.
3.Mechanism of Chaihu Shugan Powder in Treatment of Depression Based on Network Pharmacology,Molecular Docking and Experimental Verification
Haiying TENG ; Yuyan YU ; Xiaoru ZHOU ; Yulu WANG
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(10):31-38
Objective To predict the mechanism of Chaihu Shugan Powder against depression based on network pharmacology and molecular docking technology;To verify them through animal experiment of chronic unpredictable mild stress(CUMS)depression model rats.Methods TCMSP was used to screen the active components of Chaihu Shugan Powder and the related targets were obtained.Disease targets were retrieved by DisGeNET,GeneCards and GEO databases.The protein-protein interaction(PPI)network construction,GO and KEGG pathway enrichment analyses were conducted to determine the action pathway of Chaihu Shugan Powder against depression.Molecular docking of main active components and potential targets was performed.The depression model was established by CUMS combined with solitary rearing method,in which Chaihu Shugan Powder and PI3K specific inhibitor LY294002 were used to intervene depression model rats.Western blot and qPCR were respectively used to detect the action pathway related proteins and mRNAs.ELISA was used to detect the contents of monoamine neurotransmitters 5-HT and NE in hippocampal tissue,and their pathways of action were integrated and analyzed.Results Totally 118 active components of Chaihu Shugan Powder against depression and 74 potential targets were screened;KEGG pathway enrichment analysis indicated that action pathway of Chaihu Shugan Powder against depression were closely related to PI3K-Akt signaling pathway,AGE-RAGE signaling pathway in diabetic complications,etc.Molecular docking showed that quercetin,kaempferol,β-sitosterol,isorhamnetin,naringenin had good binding activity with AKT1,PIK3CA,GSK3B,IL6,IL1B.The animal experiments showed that Chaihu Shugan Powder could improve the depression-like behavior of model rats,increase the phosphorylation levels of PI3K and Akt in hippocampal tissue,down-regulate the expression of GSK3β,and increase the contents of 5-HT and NE.LY294002 could reverse the effect of Chaihu Shugan Powder.The results of integration analysis showed that PI3K/Akt signaling pathway of Chaihu Shugan Powder was closely related to metabolism of 5-HT and NE.Conclusion Chaihu Shugan Powder can exert antidepressant effects by activating the PI3K/Akt signaling pathway,inhibiting the expression of GSK3β,and increasing the levels of monoamine neurotransmitters 5-HT and NE.
4.Establishment of mouse models of lymphoma with dual-labeled EBV-immortalized lymphoblastoid cell lines by intravenous versus subcutaneous injection
Lanlan FANG ; Ting DONG ; Ying ZHOU ; Yulu SUN ; Yang GAO ; Yunqing XIONG ; Chaojiang GU
Chinese Journal of Clinical Oncology 2023;50(24):1243-1247
Objective:To establish a green fluorescent protein(GFP)and firefly luciferase(Luc)double-labeled Epstein-Barr virus(EBV)infec-ted B lymphoblastoid cell lines(B-LCL)and apply them to mouse models,then compare the advantages and disadvantages of models inocu-lated by intravenous(IV)or subcutaneous(SC).Methods:B lymphoblastoid cell lines double-tagged with GFP/Luc(B-LCL-GL)were con-structed through lentivirus transduction,puromycin intervention.Subcutaneous xenograft and hematogenous metastasis models were re-spectively established by subcutaneous or intravenous injection of B-LCL-GL cells at three concentrations in(NOD)/Prkdcscid/IL-2Rγnull(NPG)mice for in vivo bioluminescence imaging.Results:In the B-LCL-GL group,the ratio of the GFP-positive cell population was 92.5%,and the average luminescence intensity was as high as 4.80E+08 Photons/s,which was considerably higher than that of untreated B-LCLs.In the hematogenous metastasis models,tumor bioluminescence was initially located in the peritoneal area and then spread throughout the en-tire body between 7 and 28 days.In the subcutaneous xenograft models,strong central and weak peripheral tumor-related biolumines-cence signal was detected on day 7 in the three groups,which then spread throughout the body on day 28 in the high-dose group.Taken to-gether,there was no significant difference in tumor progression between the two routes of administration when using the same dose of B-LCL-GL cells.However,the survival analysis indicated that the IV injection group,in which all the mice ultimately died,had a shorter time frame for testing than that of the SC injection group,in which the mice survived until day 100 in the low-dose and medium-dose groups,thus allowing for long-term testing.Conclusions:GFP and Luc dual-positive B-LCLs were successfully established to generate hematogenous metastasis and subcutaneous xenograft models,which allow the monitoring of the location and size of lymphomas in vivo.It provide plat-form for the study of tumor characteristics and selecting anti-tumor drugs.
5.Research progress of digital integration of geriatric patients in the context of smart outpatient service
Yulu CHEN ; Liling XIE ; Tingting ZHOU ; Huanhuan HUANG ; Qinghua ZHAO ; Mingzhao XIAO
Chinese Journal of Modern Nursing 2023;29(4):538-542
This article reviews the overview of digital integration of geriatric patients and related influencing factors, the current situation of smart outpatient service, and the aging measures of smart outpatient service, with a view to providing reference for Chinese scholars to further study digital integration of geriatric patients.
6.Relation factor analysis for the short-term preservation of ipsilateral renal function after partial nephrectomy
Yixin HUANG ; Xiangpeng ZOU ; Zhiling ZHANG ; Kang NING ; Xin LUO ; Longbin XIONG ; Yulu PENG ; Zhaohui ZHOU ; Pei DONG ; Shengjie GUO ; Hui HAN ; Fangjian ZHOU
Chinese Journal of Surgery 2023;61(12):1099-1103
Objectives:To analyze the factors relative to the short-term preservation of ipsilateral renal function after partial nephrectomy.Methods:The clinical data of 83 patients who were treated with partial nephrectomy from December 2014 to December 2019 in the Department of Urology, Sun Yat-sen University Cancer Center were retrospectively analyzed. There were 54 males and 29 females, aging ( M (IQR)) 49 (17) years (range: 27 to 74 years). The ischemia time in operation was 25 (18) minutes (range: 10 to 67 minutes). Emission computed tomography scan and CT scan were performed before (within 1 month) and after (3 to 12 months) surgery. The volume of the ipsilateral and contralateral kidney was measured on the basis of preoperative and postoperative CT scans. The glomerular filtration rate (GFR) specifically in each kidney was estimated by emission computed tomography. Recovery from ischemia is determined by the formula: GFR preservation/volume saved×100%. Linear regression was used to explore the factors ralative to the short-term preservation of ipsilateral renal function after partial nephrectomy. Results:The GFR preservation of the ipsilateral kidney was 80.9 (25.2) % (range: 31.0% to 109.4%). The volume loss of the kidney resulted in a decrease of 12.0% (5.8 ml/(min×1.96 m 2)) of GFR, while the ischemic injury resulted in a decrease of 6.5% (2.5 ml/(min×1.96 m 2)) of GFR. The volume saved from the ipsilateral kidney was 87.1 (12.9) % (range: 27.0% to 131.7%). Recovery from ischemia was 93.5 (17.5) % (range:44.3% to 178.3%). In multivariate analysis, GFR preservation of the ipsilateral kidney was significantly correlated with the volume saved of the ipsilateral kidney ( β=0.383, 95% CI: 0.144 to 0.622, P=0.002). It was not related to the ischemia time ( β=0.046, 95% CI:-0.383 to 0.475, P=0.831). Conclusion:In the condition of limited ischemic time, in the short term ipsilateral renal function after partial nephrectomy is mainly determined by the loss of kidney volume, while ischemic injury only plays a minor role.
7.Relation factor analysis for the short-term preservation of ipsilateral renal function after partial nephrectomy
Yixin HUANG ; Xiangpeng ZOU ; Zhiling ZHANG ; Kang NING ; Xin LUO ; Longbin XIONG ; Yulu PENG ; Zhaohui ZHOU ; Pei DONG ; Shengjie GUO ; Hui HAN ; Fangjian ZHOU
Chinese Journal of Surgery 2023;61(12):1099-1103
Objectives:To analyze the factors relative to the short-term preservation of ipsilateral renal function after partial nephrectomy.Methods:The clinical data of 83 patients who were treated with partial nephrectomy from December 2014 to December 2019 in the Department of Urology, Sun Yat-sen University Cancer Center were retrospectively analyzed. There were 54 males and 29 females, aging ( M (IQR)) 49 (17) years (range: 27 to 74 years). The ischemia time in operation was 25 (18) minutes (range: 10 to 67 minutes). Emission computed tomography scan and CT scan were performed before (within 1 month) and after (3 to 12 months) surgery. The volume of the ipsilateral and contralateral kidney was measured on the basis of preoperative and postoperative CT scans. The glomerular filtration rate (GFR) specifically in each kidney was estimated by emission computed tomography. Recovery from ischemia is determined by the formula: GFR preservation/volume saved×100%. Linear regression was used to explore the factors ralative to the short-term preservation of ipsilateral renal function after partial nephrectomy. Results:The GFR preservation of the ipsilateral kidney was 80.9 (25.2) % (range: 31.0% to 109.4%). The volume loss of the kidney resulted in a decrease of 12.0% (5.8 ml/(min×1.96 m 2)) of GFR, while the ischemic injury resulted in a decrease of 6.5% (2.5 ml/(min×1.96 m 2)) of GFR. The volume saved from the ipsilateral kidney was 87.1 (12.9) % (range: 27.0% to 131.7%). Recovery from ischemia was 93.5 (17.5) % (range:44.3% to 178.3%). In multivariate analysis, GFR preservation of the ipsilateral kidney was significantly correlated with the volume saved of the ipsilateral kidney ( β=0.383, 95% CI: 0.144 to 0.622, P=0.002). It was not related to the ischemia time ( β=0.046, 95% CI:-0.383 to 0.475, P=0.831). Conclusion:In the condition of limited ischemic time, in the short term ipsilateral renal function after partial nephrectomy is mainly determined by the loss of kidney volume, while ischemic injury only plays a minor role.
8.Accurate quantification of 3'-terminal 2'-O-methylated small RNAs by utilizing oxidative deep sequencing and stem-loop RT-qPCR.
Yan KONG ; Huanhuan HU ; Yangyang SHAN ; Zhen ZHOU ; Ke ZEN ; Yulu SUN ; Rong YANG ; Zheng FU ; Xi CHEN
Frontiers of Medicine 2022;16(2):240-250
The continuing discoveries of novel classes of RNA modifications in various organisms have raised the need for improving sensitive, convenient, and reliable methods for quantifying RNA modifications. In particular, a subset of small RNAs, including microRNAs (miRNAs) and Piwi-interacting RNAs (piRNAs), are modified at their 3'-terminal nucleotides via 2'-O-methylation. However, quantifying the levels of these small RNAs is difficult because 2'-O-methylation at the RNA 3'-terminus inhibits the activity of polyadenylate polymerase and T4 RNA ligase. These two enzymes are indispensable for RNA labeling or ligation in conventional miRNA quantification assays. In this study, we profiled 3'-terminal 2'-O-methyl plant miRNAs in the livers of rice-fed mice by oxidative deep sequencing and detected increasing amounts of plant miRNAs with prolonged oxidation treatment. We further compared the efficiency of stem-loop and poly(A)-tailed RT-qPCR in quantifying plant miRNAs in animal tissues and identified stem-loop RT-qPCR as the only suitable approach. Likewise, stem-loop RT-qPCR was superior to poly(A)-tailed RT-qPCR in quantifying 3'-terminal 2'-O-methyl piRNAs in human seminal plasma. In summary, this study established a standard procedure for quantifying the levels of 3'-terminal 2'-O-methyl miRNAs in plants and piRNAs. Accurate measurement of the 3'-terminal 2'-O-methylation of small RNAs has profound implications for understanding their pathophysiologic roles in biological systems.
Animals
;
High-Throughput Nucleotide Sequencing
;
Humans
;
Methylation
;
Mice
;
MicroRNAs/genetics*
;
Oxidative Stress
;
RNA, Small Interfering/metabolism*
;
Real-Time Polymerase Chain Reaction
9.Research on the application effect of OBE concept on the teaching of otorhinolaryngology nursing
Jie LIU ; Fanghong XIE ; Yin ZHOU ; Yulu CHEN
Chinese Journal of Medical Education Research 2022;21(2):232-236
Objective:To observe the application effect of outcome-based education (OBE) concept on the teaching of otorhinolaryngology nursing.Methods:A total of 97 nursing interns from the Department of Otorhinolaryngology in The Second Affiliated Hospital of Army Medical University were selected as the research objects. Among them, 46 ones from March 2017 to February 2019 were collected as the control group, and 51 ones from March 2019 to February 2021 as the observation group. The control group adopted traditional nursing clinical teaching, and the observation group adopted the nursing clinical teaching based on the OBE concept. All the nursing students had an internship for 3 weeks, and had an evaluation in terms of the clinical communication ability of the two groups of nursing students when they leave the department (the nursing students' clinical communication ability assessment scale), the daily life problem solving ability (simplified Chinese version of the daily life problem solving questionnaire), theoretical and operational assessment results, and the internship satisfaction (nursing student internship satisfaction scale). SPSS 19.0 was used for independent-sample t test. Results:When leaving the department, the observation group's clinical communication ability scores were significantly higher than those of the control group in such dimensions as establishing a harmonious relationship, keen listening, confirming patient problems, participating together, transmitting effective information, and verifying feelings ( P<0.05). The scores of simplified Chinese version of the daily life problem solving questionnaire of rational problem solving and positive problem orientation of the observation group were significantly higher than those of the control group ( P<0.05), while the scores of negative problem orientation, avoidance style and impulsivity/carelessness style were significantly lower than those of the control group ( P<0.05). The scores of theoretical and operational evaluations of the observation group were significantly higher than those of the control group ( P<0.05). The practice satisfaction scores on each dimension of the observation group, including clinical teaching, classroom teaching, and internship plan, support and resources were significantly higher than those of the control group ( P<0.05). Conclusion:The OBE concept applied in the teaching of otorhinolaryngology nursing can enhance the clinical communication ability and daily life problem-solving ability of nursing students, increase the theoretical and operational assessment results, and improve the satisfaction of internship.
10.Evaluation of the metabolism of PEP06,an endostatin-RGDRGD 30-amino-acid polypeptide and a promising novel drug for targeting tumor cells
Liyun NIU ; Huiyu ZHOU ; Yueru LIAN ; Ya GAO ; Yulu LIU ; Ruolan GU ; Zhuona WU ; Xiaoxia ZHU ; Hui GAN ; Zhiyun MENG ; Guifang DOU
Journal of Pharmaceutical Analysis 2022;12(5):766-773
PEP06 is a novel endostatin-Arg-Gly-Asp-Arg-Gly-Asp(RGDRGD)30-amino-acid polypeptide featuring a terminally fused RGDRGD hexapeptide at the N terminus.The active endostatin fragment of PEPO6 directly targets tumor cells and exerts an antitumoral effect.However,little is known about the kinetics and degradation products of PEP06 in vitro or in vivo.In this study,we investigated the in vitro metabolic stability of PEP06 after it was incubated with living cells obtained from animals of different species;we further identified the degradation characteristics of its cleavage products.PEP06 underwent rapid enzymatic degradation in multiple types of living cells,and the liver,kidney,and blood play important roles in the metabolism and clearance of the peptides resulting from the molecular degradation of PEP06.We identified metabolites of PEP06 using full-scan mass spectrometry(MS)and tandem MS(MS2),wherein 43 metabolites were characterized and identified as the degradation metabolites from the parent peptide,formed by successive losses of amino acids.The metabolites were C and N terminal truncated products of PEP06.The structures of 11 metabolites(M6,M7,M16,M17,M21,M25,M33,M34,M39,M40,and M42)were further confirmed by comparing the retention times of similar full MS spectrum and MS2 spectrum information with reference standards for the synthesized metabolites.We have demonstrated the metabolic stability of PEP06 in vitro and identified a series of potentially bioactive downstream metabolites of PEP06,which can support further drug research.


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