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Objective To investigate the change rule of T1ρ value in the process of lumbar intervertebral disc degeneration(IVDD)based on Pfirrmann grading by Meta-analysis.Methods PubMed,EMBASE,Cochrane Library,CNKI,Wanfang Data,VIP and Sinomed were searched to collect studies on quantitative assessment of IVDD using T1ρ imaging technology.The retrieval time limit was from the establishment of the database to December 20,2022.Meta-analysis was performed using RevMan 5.4 and Stata 14.0 software.Results A total of 12 articles were included,and the numbers of Pfirrmann grade Ⅰ-Ⅴ lumbar discs were 316,1 460,769,430 and 98,respectively.T1ρ relaxation time decreased gradually with the increase of the grade of degeneration.The T1ρ values of grade Ⅰlumbar discs were significantly higher than those of grade Ⅱ lumbar discs[weighted mean difference(WMD)=14.55,95%confidence interval(CI)6.35-22.75,P<0.01],and the T1ρ values of grade Ⅱ lumbar discs were significantly higher than those of grade Ⅲlumbar discs(WMD=34.20,95%CI 27.05-41.34,P<0.01).The T1ρ values of grade Ⅲ lumbar discs were significantly higher than that of grade Ⅳ lumbar discs(WMD=22.94,95%CI 17.08-28.80,P<0.01).The T1ρ values of grade Ⅳ lumbar discs were significantly higher than that of grade Ⅴ lumbar discs(WMD=9.35,95%CI 6.81-11.89,P<0.01).Conclusion T1ρ imaging technology can objectively and quantitatively evaluate degeneration at different stages,especially sensitive to IVDD in the early and middle stages,which can provide imaging evidence for clinical diagnosis of early IVDD.
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BACKGROUND:High-methionine diet can cause liver injury in Cbs+/-mice,and hyperhomocystinemia is related to the occurrence and progression of various liver-related diseases,such as hepatic steatosis,autoimmune hepatitis,and alcoholic fatty liver disease.MicroRNAs(miRNAs)are involved in various cellular processes including cell survival,differentiation and autophagy,which are of great significance. OBJECTIVE:To investigate the critical role of miR-144-3p on Cbs+/-mouse hepatocyte autophagy induced by high methionine die. METHODS:(1)Ten male cystathione-β-synthase normal(Cbs+/+)mice and another 10 male mice with single gene knockout(Cbs+/-)of similar body mass,4 weeks of age,were fed a high-methionine diet and executed after 12 weeks to take liver tissue.(2)Human hepatocytes(HL-7702)were cultured in vitro and divided into control[0 μmol/L homocysteine(Hcy)],Hcy(100 μmol/L Hcy),mimic-NC(transfected with mimic-NC),mimic-NC + Hcy(mimic-NC transfecton+100 μmol/L Hcy),miR-144-3p mimic(transfected with miR-144-3p mimic),and miR-144-3p mimic + Hcy(miR-144-3p mimic transfection+100 μ mol/L Hcy),inhibitor-NC(transfected with inhibitor-NC),inhibitor-NC + Hcy(inhibitor-NC transfection + 100 μmol/L Hcy),miR-144-3p inhibitor(transfected with miR-144-3p inhibitor),and miR-144-3p inhibitor + Hcy(miR-144-3p inhibitor transfection + 100 μmol/L Hcy).Quantitative real-time PCR was used to detect the expression of miR-144-3p in liver tissue and hepatocytes.After transfection of miR-144-3p mimic or inhibitor,quantitative real-time PCR and western blot were used to detect the transfection efficiency of miR-144-3p and its effect on the expression of autophagy-related proteins LC3B and p62.The levels of alanine transferase and aspartate aminotransferase in hepatocyte supernatants were determined by enzyme linked immunosorbent assay.The correlation between the expression of miR-144-3 in hepatocyte and the levels of alanine transferase and aspartate aminotransferase in hepatocyte supernatants were analyzed by Pearson correlation analysis. RESULTS AND CONCLUSION:Compared with the Cbs+/+ group and control group,the expression of miR-144-3p in the liver tissue of the Cbs+/-group and in hepatocytes of the Hcy group was decreased(P<0.01).The expression of LC3B-Ⅱ/Ⅰ was decreased in hepatocyte after transfection of miR-144-3p mimic,while the protein expression of p62 was increased(P<0.01).The opposite results were obtained after transfection of miR-144-3p inhibitor(P<0.01).Compared with the mimic-NC group,the levels of alanine transferase and aspartate aminotransferase were decreased in the miR-144-3p mimic group(P<0.01),while the opposite results were obtained in the inhibitor-NC group(P<0.01).The expression of miR-144-3p in hepatocytes was negatively correlated with the levels of alanine transferase(P<0.01,r=-0.887 6)and aspartate aminotransferase(P<0.01,r=-0.829 9)in the supernatant of hepatocytes.To conclude,Hcy promotes hepatocyte autophagy by inhibiting the expression of miR-144-3p,which subsequently aggravates liver injury.
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BACKGROUND:Quercetin plays an important role in the proliferation and differentiation of bone marrow mesenchymal stem cells,but less research has been done on its mechanism of promoting the migration of bone marrow mesenchymal stem cells. OBJECTIVE:To study the effect of quercetin on the migration of human bone marrow mesenchymal stem cells through in vitro experiments,and to explore the regulatory role of CCR1 and CXCR4. METHODS:Human bone marrow mesenchymal stem cells were selected as experimental subjects.CCK8 assay was used to detect the effect of quercetin on the proliferative activity of human bone marrow mesenchymal stem cells.Cell scratch assay and Transwell assay were used to detect the in vitro invasive and migratory abilities of human bone marrow mesenchymal stem cells after quercetin treatment,respectively.The role of quercetin in relation to CCR1 and CXCR4 was demonstrated with the help of molecular docking technology.Western blot assay and real-time fluorescence quantitative PCR were used to detect the migration-related chemokine expression after quercetin treatment. RESULTS AND CONCLUSION:(1)5 and 10 μmol/L quercetin could significantly promote the proliferation of human bone marrow mesenchymal stem cells,and the drug concentration of 10 μmol/L resulted in the highest cell proliferation efficiency.(2)To better explore the dose-effect relationship of quercetin affecting the migration of human bone marrow mesenchymal stem cells,5 and 10 μmol/L quercetin were selected for the subsequent experiments,and ligustrazine was used as the positive control drug,and the experiments were divided into blank control group,5 μmol/L quercetin group,10 μmol/L quercetin group,and 100 μmol/L ligustrazine group.(3)In vitro migration and invasion ability of human bone marrow mesenchymal stem cells were elevated in a concentration-dependent manner after quercetin treatment,and the migration effect of 10 μmol/L quercetin group was better than that of ligustrazine group.(4)The molecular docking results suggested that there was a strong interaction between quercetin and CCR1 and CXCR4.(5)Quercetin could up-regulate the expression of CCR1 and CXCR4 proteins and mRNA.(6)This study confirmed at the cellular level that quercetin could promote the migration of human bone marrow mesenchymal stem cells by targeting CCR1 and CXCR4.
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@#Objective To analyze the distribution of common allergens in children with allergic rhinitis(AR)in Hangzhou,and to provide reference for its prevention and treatment.Methods From January 2020 to December 2022,13 521 children who were diagnosed with AR and underwent in vitro serum specific immunoglobulin E(sIgE)detection in Affiliated Hangzhou First People's Hospital,School of Medicine,Westlake University were selected as the research objects.The positive rates of allergens in children with AR of different genders,ages and seasons were compared.Results Among 13 521 children,the positive rate of sIgE was 54.49%(7367/13 521),of which 64.82%were allergic to only one allergen.Among the 19 common allergens,the top three overall positive rates were household dust mite(44.27%),milk(14.62%),and mixed grass(4.82%).The positive rates of allergens of house dust mites,cat hair dander,mulberry,mold combination,tree pollen combination,amaranth,cockroach,milk,shrimp,crab,pineapple,shellfish and mango in male children were significantly higher than those in female children(P<0.05).The positive rates of allergens of house dust mite,mixed grass,cat hair dander,mulberry,mold combination,egg white,shrimp,crab,pineapple,cashew nuts and shellfish in different age groups were statistically significant(P<0.05).July and August were the two months with the highest allergen positive rate.The allergen positive rates of house dust mite,dog and cat hair dander were the highest in summer,and the allergen positive rate of plants was consistent with the flowering season.The sIgE concentration of house dust mite(77.87%)was mainly grade 3 and above.The sIgE concentration of other allergens was mainly grade 1 and 2.Conclusion Dust mites and milk are the most common allergens in children with AR in Hangzhou,and the distribution of allergens varies with gender,age and season.Allergen detection can provide a more accurate plan for the diagnosis,prevention and treatment of AR.
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OBJECTIVE@#Melittin, a cell-penetrating peptide, improves the efficiency of many non-viral gene delivery vectors, yet its application in viral vectors has not been well studied. The non-pathogenic recombinant adeno-associated virus (rAAV) vector is an ideal in vivo gene delivery vector. However, its full potential will only be achieved after improvement of its transduction efficiency. To improve the transduction efficiency of rAAV2 vectors, we attempted to develop a melittin-based rAAV2 vector delivery strategy.@*METHODS@#The melittin peptide was inserted into the rAAV2 capsid either in the loop VIII of all viral proteins (VPs) or at the N terminus of VP2. Various rAAV2-gfp or -fluc vectors were subjected to quantitative real-time polymerase chain reaction and Western blot assays to determine their titers and integrity of capsid proteins, respectively. Alternatively, the vectors based on wild-type capsid were pre-incubated with melittin, followed by transduction of cultured cells or tail vein administration of the mixture to C57BL/6 and BALB/c nude mice. In vivo bioluminescence imaging was performed to evaluate the transgene expression.@*RESULTS@#rAAV2 vectors with melittin peptide inserted in the loop VIII of VPs had low transduction efficiency, probably due to dramatically reduced ability to bind to the target cells. Fusing the melittin peptide at the N-terminus of VP2 produced vectors without the VP2 subunit. Interestingly, among the commonly used rAAV vectors, pre-incubation of rAAV2 and rAAV6 vectors with melittin significantly enhanced their transduction efficiency in HEK293 and Huh7 cells in vitro. Melittin also had the ability to increase the rAAV2-mediated transgene expression in mouse liver in vivo. Mechanistically, melittin did not change the vector-receptor interaction. Moreover, cell counting kit-8 assays of cultured cells and serum transaminase levels indicated melittin had little cytotoxicity.@*CONCLUSION@#Pre-incubation with melittin, but not insertion of melittin into the rAAV2 capsid, significantly enhanced rAAV2-mediated transgene expression. Although further in vivo evaluations are required, this research not only expands the pharmacological potential of melittin, but also provides a new strategy to improve gene therapy mediated by rAAV vectors.
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Ratones , Animales , Humanos , Meliteno/genética , Dependovirus/genética , Serogrupo , Células HEK293 , Ratones Desnudos , Ratones Endogámicos C57BL , Transgenes , Vectores Genéticos/genéticaRESUMEN
Lipid homeostasis is considered to be related to intestinal metabolic balance, while its role in the pathogenesis and treatment of ulcerative colitis (UC) remains largely unexplored. The present study aimed to identify the target lipids related to the occurrence, development and treatment of UC by comparing the lipidomics of UC patients, mice and colonic organoids with the corresponding healthy controls. Here, multi-dimensional lipidomics based on LC-QTOF/MS, LC-MS/MS and iMScope systems were constructed and used to decipher the alteration of lipidomic profiles. The results indicated that UC patients and mice were often accompanied by dysregulation of lipid homeostasis, in which triglycerides and phosphatidylcholines were significantly reduced. Notably, phosphatidylcholine 34:1 (PC34:1) was characterized by high abundance and closely correlation with UC disease. Our results also revealed that down-regulation of PC synthase PCYT1α and Pemt caused by UC modeling was the main factor leading to the reduction of PC34:1, and exogenous PC34:1 could greatly enhance the fumarate level via inhibiting the transformation of glutamate to N-acetylglutamate, thus exerting an anti-UC effect. Collectively, our study not only supplies common technologies and strategies for exploring lipid metabolism in mammals, but also provides opportunities for the discovery of therapeutic agents and biomarkers of UC.
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Objective:To investigate the expression, methylation and prognosis of DKK2 in non-small cell lung cancer, and also its effect and correlation with the sensitivity of hypofractionated radiotherapy sensitivity in non-small cell lung cancer.Methods:qPCR, online database and Kaplan-Meier survival curve were used to detect the expression, methylation and prognosis of DKK2 in NSCLC samples. A549 cells was set as the research objects, and cloning formation experiment and Western blot were used to evaluated the effects of DKK2 on hypofractionated radiotherapy in NSCLC.Results:Compared with the normal tissues, the expression of DKK2 mRNA in NSCLC samples was down-regulaged [ (0.00042±0.0001) vs (0.00065±0.0002), P<0.001]. Data taken from an online methylation database showed that compared with normal tissue, DKK2 hypermethylated in NSCLC, and its methylation was significantly negatively correlated with the mRNA expression. Downregulated DKK2 expression was inversely correlated with its methylation status ( P=0.034). The hypofractionated radiotherapy sensitivity of NSCLC patients was 53.3%. Compared with radiosensitivity group, DKK2 mRNA expression was significantly down-regulated in radioresistance group[ (0.00064±0.0002) vs (0.00043±0.0002), P<0.001]. The progression free survival of radiotherapy sensitive group was better than that of radiotherapy resistant group (median PFS: 21.4 months vs 4.6 months). Ectopic expression of DKK2 in A549 lines inhibited colony formation after irradiation with 4 Gy X-ray radiotherapy. Western blot further showed that restoration of DKK2 expression resulted in upregulation of DNA damage markers γ-H2AX[ (1.00±0.24) vs (3.22±0.41), P<0.001], and the difference was statistically significant. Conclusion:DKK2 expression is downregulated in NSCLC due to methylation, which may be acted as an important target to predict the hypofractionated radiotherapy sensitivity of NSCLC.
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With high incidence, high disability rate and serious impact on patients' quality of life, advanced primary angle-closure glaucoma (PACG) with cataract is a severe eye disease in China and its main treatment method is surgery.Phacoemulsification cataract extraction and intraocular lens implantation (PEI) combined with trabeculectomy has been used to treat advanced PACG with cataract, but there are many postoperative complications.Recently, combined PEI, goniosynechialysis (GSL) and goniotomy (GT) has been proven to be a safe and effective surgical treatment for advanced PACG with cataract.At present, the combined PEI+ GSL+ GT surgery has been widely applied, but there is still a lack of uniform standards for its clinical application.Therefore, it is necessary to formulate a detailed and complete recommendation of the surgical procedures for PEI+ GSL+ GT, to standardize its application in clinical practice.Based on the analysis of the existing problems, some glaucoma experts in China have formulated detailed and complete operation norms, as well as expert recommendations on surgical indications and contraindications, anesthetic methods, surgical techniques and perioperative medication to standardize the application process of PEI+ GSL+ GT in clinical practice.
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Minimally invasive glaucoma surgery (MIGS) has been successfully incorporated in clinical practice in recent years.Increasing evidence shows that MIGS also plays an increasingly important role in the treatment of primary angle-closure glaucoma (PACG). Surgical peripheral iridectomy (SPI) plus goniosynechialysis (GSL) and goniotomy (GT), as a new procedure, has been proven to be safe and effective in the treatment of PACG with no or mild cataracts.However, there is still a lack of uniform standards for indications, surgical procedures, and perioperative medication.Therefore, it is necessary to formulate a detailed and complete expert recommendations on surgical procedures to standardize the application of combined SPI+ GSL+ GT in the treatment.Some experts in glaucoma treatment and management in China have discussed the current problems and developing trend in MIGS for PACG and put forward the expert recommendations of standard process, including indications, anaesthetic methods, surgical site, operating procedure and rational administration of drugs in perioperation, in order to standardize the medical process of clinicians using combined SPI+ GSL+ GT in PACG treatment and lay a foundation for better evaluation of the efficacy of MIGS.
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Objective:To evaluate the preliminary effectiveness and safety of surgical peripheral iridectomy (SPI) combined with goniosynechilysis (GSL) and goniotomy (GT) in the treatment of advanced primary angle-closure glaucoma (PACG).Methods:A multicenter observational case series study was performed.Thirty-five eyes of 27 patients with advanced PACG, who underwent SPI+ GSL+ GT with a follow-up of at least 6 months, were included from August 2021 to January 2022 at Zhongshan Ophthalmic Center, Handan City Eye Hospital, Shijiazhuang People's Hospital, West China Hospital of Sichuan University, and the Third Affiliated Hospital of Chongqing Medical University.The mean follow-up time was 9(7, 10) months.Pre- and post-operative best corrected visual acuity (BCVA) and intraocular pressure (IOP) were measured with an ETDRS chart and a Goldmann applanation tonometer, respectively.The number of anti-glaucoma medications applied before and after surgery was recorded, and the complications after surgery were analyzed.Success rate of surgery was calculated.Complete surgical success was defined as an IOP of 5-18 mmHg (1 mmHg=0.133 kPa) and 20% reduction from baseline without anti-glaucoma medication or reoperation.Qualified success was defined as achieving criterion of complete success under anti-glaucoma medications.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Zhongshan Ophthalmic Center, Sun Yat-sen University (No.2021KYPJ177). Written informed consent was obtained from each subject.Results:The mean preoperative IOP was (30.83±8.87)mmHg, which was significantly decreased to (15.69±3.70)mmHg at 6 months after the surgery ( t=8.588, P<0.001), with a 44.00% (34.78%, 60.00%) decline of 13.00(8.00, 21.00)mmHg.The median number of anti-glaucoma medications was significantly reduced from 2(0, 3) preoperatively to 0 (0, 1) postoperatively ( Z=-3.659, P<0.001). The mean preoperative and postoperative 6-month BCVA were 0.80(0.63, 1.00) and 0.80(0.60, 1.00), respectively, showing no significant difference ( Z=-0.283, P=0.777). Complete surgical success rate was 62.86%(22/35), and the qualified success rate was 91.43%(32/35). Surgical complications mainly included hyphema (6/35), IOP spike (3/35), and shallow anterior chamber (4/35). There was no vision-threatening complication. Conclusions:SPI+ GSL+ GT is preliminarily effective and safe in the treatment of advanced PACG, which provides a new option for PACG.
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Minimally invasive glaucoma surgery (MIGS) has been successfully incorporated in clinical practice in recent years.Increasing evidence shows that it also plays an important role in the treatment of primary angle-closure glaucoma (PACG). Goniosynechialysis (GSL) is a key surgical procedure used by MIGS for PACG, which involves separating the peripheral anterior synechia and reopening the angle.However, there is still a lack of uniform standards for indications and surgical procedures.Therefore, it is necessary to formulate a detailed and complete expert consensus on surgical procedures to standardize the application of clinicians in the treatment.
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AIM: To analyze the current status, hotspots and trends of studies on the treatments of diabetic retinopathy.METHODS: Relevant literatures on diabetic retinopathy in Chinese National Knowledge Infrastructure(CNKI)and Web of Science core collection database were retrieved from creation to June 15, 2023, and CiteSpace 6.2.R2 and VOSviewer were used to conduct visualized analysis with the country/issuing institution, research author and keywords.RESULTS: A total of 5 919 Chinese literatures and 11 475 English literatures were included. The top three countries with global publications are the United States, China and the United Kingdom, respectively. The top three institutions for issuing articles at abroad are Harvard Medical School, Harvard University and Johns Hopkins University, while the top three institutions for issuing articles in China are the Eye Hospital of China Academy of Chinese Medical Science, Hunan University of Chinese Medicine, and Zhongshan Ophthalmic Center of Sun Yat-sen University. The research results of high-frequency keywords in both Chinese and English show that the laser photocoagulation, vitrectomy, traditional Chinese medicine therapy, vascular endothelial growth factor and ranibizumab are research hotspots.CONCLUSIONS: In recent years, the research hotspots of diabetic retinopathy mainly focus on surgery, vascular protective agents, traditional Chinese medicine therapy, anti-vascular endothelial growth factor, etc., and the research trend mainly focuses on anti-vascular endothelial growth factor drugs.
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Nonalcoholic steatohepatitis (NASH) is a spectrum of chronic liver disease characterized by hepatic lipid metabolism disorder. Recent reports emphasized the contribution of triglyceride and diglyceride accumulation to NASH, while the other lipids associated with the NASH pathogenesis remained unexplored. The specific purpose of our study was to explore a novel pathogenesis and treatment strategy of NASH via profiling the metabolic characteristics of lipids. Herein, multi-omics techniques based on LC-Q-TOF/MS, LC-MS/MS and MS imaging were developed and used to screen the action targets related to NASH progress and treatment. A methionine and choline deficient (MCD) diet-induced mouse model of NASH was then constructed, and Schisandra lignans extract (SLE) was applied to alleviate hepatic damage by regulating the lipid metabolism-related enzymes CES2A and CYP4A14. Hepatic lipidomics indicated that MCD-diet led to aberrant accumulation of phosphatidylethanolamines (PEs), and SLE could significantly reduce the accumulation of intrahepatic PEs. Notably, exogenous PE (18:0/18:1) was proved to significantly aggravate the mitochondrial damage and hepatocyte apoptosis. Supplementing PE (18:0/18:1) also deteriorated the NASH progress by up regulating intrahepatic proinflammatory and fibrotic factors, while PE synthase inhibitor exerted a prominent hepatoprotective role. The current work provides new insights into the relationship between PE metabolism and the pathogenesis of NASH.
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Objective:To investigate the role of microchromosome maintenance protein 5 (MCM5) in promoting malignant progression and its mechanism in glioblastoma.Methods:(1) Three freshly excised brain tissues from non-tumor patients and 3 grading IV glioblastoma tissues were collected in our hospital from September 2020 to September 2021; mass spectrometry and quantitative proteomic analysis were performed to screen differentially expressed proteins for functional enrichment analysis. (2) The target protein MCM5, which was highly expressed in glioblastoma, was screened on the basis of proteomics, and its expression in glioblastoma was verified using The Cancer Genome Atlas (TCGA) database and further validated at the mRNA level in the collected clinical specimens. (3) U251 cells were divided into negative control group, knockdown group-1 (si-1 group) and knockdown group-2 (si-2 group) by siNRA transfection. The regulation role of MCM5 in malignant phenotype of glioblastoma was detected by CCK-8 assay, clone formation assay, 5-ethynyl-2'-deoxyuridine (EdU)staining, Transwell invasion assay and flow cytometry. (4) The transcriptome data of glioma patients from TCGA database were used to explore the possible molecular mechanisms of MCM5 regulation in the malignant process of glioblastoma by gene set enrichment analysis (GSEA) algorithm.Results:(1) In clinical samples of glioblastoma, 322 up-regulated proteins and 94 down-regulated proteins were screened out; MCM5 was highly expressed in these 3 glioblastoma samples. (2) Based on TCGA database, results of 163 patients with glioblastoma and 207 patients with non-tumor brain tissues showed that MCM5 expression was statistically up-regulated in glioblastoma ( t=3.340, P<0.001). Real-time quantitative PCR results of 3 glioblastoma tissues and 3 non-tumor brain tissues clinically collected in our hospital also indicated that significantly increased MCM5 expression in glioblastoma was noted as compared with that in the non-tumor brain tissues ( t=3.876, P<0.001). (3) As compared with the negative control group, the si-1 and si-2 groups had significantly decreased MCM5 mRNA and protein expressions, significantly lower proliferation rate 5 d after inoculation, statistically decreased number of cell clones, significantly decreased proportion of EdU positive cells, and significantly increased proportion of cells at G1 phase, and significantly impaired migration ability ( P<0.05). (4) GSEA analysis showed that mRNA in MCM5 high expression group was enriched in DNA damage repair gene, E2F target gene, MYC target gene, epithelial-mesenchymal transformation (EMT), nterleukin 6-Janus kinase-signal transduction and transcription activation factor 3 (IL6-JAK-STAT3), interferon, KRAS, NOTCH, transforming growth factor-β (TGF-β), Wnt/β-Catenin and other characteristic genes. Conclusion:MCM5 is highly expressed in glioblastoma, and MCM5 regulates the malignant progression of glioblastoma through multiple mechanisms including E2F, MYC, EMT, and Wnt/β-Catenin.
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@#An innovative approach to quantitatively analyze the histamine and its precursor histidine simultaneously in biological matrices was established for the first time based on double adsorption combined with high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).The internal standard was 2-dihydroxybenzoic acid (DHB).The plasma and brain tissue homogenate was protein precipitated with 3-fold acetonitrile, and the supernatant was then sampled for injection analysis.The chromatographic separation of the target components was achieved on an amino chromatography column (ODS-SPXBridge? Amide).Gradient elution was carried out with the mobile phase consisting of solvent A (0.1% formic acid and 1mmol/L ammonium formate in water) and solvent B (acetonitrile).Mass spectrometry was employed for quantitative analysis with ESI ion source in multiple reaction monitoring (MRM) mode.In order to improve the specificity and accuracy, activated carbon and calcite were used for the double adsorption of biological matrices for the first time.The adsorbed matrix was then used for methodology validation.The results showed that histamine and histidine were linear in the quantitative range (correlation coefficient r ≥ 0.999).Accuracy, precision, extraction recovery, matrix effect and stability all met the requirements of biological sample analysis.All results suggested that the present method could not only be efficiently and reliably used for simultaneous quantitative analysis of histamine and histidine in biological samples, but also provide reference for the detection of other endogenous substances.
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Peptides that are composed of dextrorotary (d)-amino acids have gained increasing attention as a potential therapeutic class. However, our understanding of the in vivo fate of d-peptides is limited. This highlights the need for whole-body, quantitative tracking of d-peptides to better understand how they interact with the living body. Here, we used mouse models to track the movement of a programmed death-ligand 1 (PD-L1)-targeting d-dodecapeptide antagonist (DPA) using positron emission tomography (PET). More specifically, we profiled the metabolic routes of [64Cu]DPA and investigated the tumor engagement of [64Cu/68Ga]DPA in mouse models. Our results revealed that intact [64Cu/68Ga]DPA was primarily eliminated by the kidneys and had a notable accumulation in tumors. Moreover, a single dose of [64Cu]DPA effectively delayed tumor growth and improved the survival of mice. Collectively, these results not only deepen our knowledge of the in vivo fate of d-peptides, but also underscore the utility of d-peptides as radiopharmaceuticals.
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Primary angle-closure glaucoma (PACG) is a common subtype of glaucoma and one of the leading causes of blindness in Asia.Trabeculectomy has been recognized as an effective filtering surgery for PACG and is widely used in clinical practice, but its high risk of postoperative complications, especially bleb scarring over time can not be ignored.Nowadays, non-bleb-based minimally invasive glaucoma surgeries (MIGS) have attracted much attention.Surgeries opening, restoring, or expanding Schlemm canal to reconstruct aqueous humor outflow pathway is one of the MIGS and able to achieve moderate intraocular pressure (IOP) reduction, which has been widely used in the treatment of primary open-angle glaucoma (POAG) for a long time.However, based on the pathogenesis of PACG and its similar pathological changes in Schlemm canal to POAG, some retrospective studies and prospective single-arm studies discovered that Schlemm canal surgery combined with phacoemulsification and/or goniosynechialysis appears to lower IOP well and safe in PACG eyes in recent years.Whether Schlemm canal surgery is also suitable or effective for PACG is getting some attention and is still controversial up to now, mostly due to some differences in pathogenesis between PACG and POAG, it is necessary to perform randomized controlled trials to confirm the efficacy of Schlemm canal surgery for PACG and upgrade the therapeutic strategy of PACG.
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@#Objective To evaluate the mid-term safety, efficacy and feasibility of perventricular device closure for subarterial ventricular septal defect. Methods Clinical data of 97 patients diagnosed with subarterial ventricular septal defect through echocardiography in West China Hospital from September 2013 to December 2015 were retrospectively analyzed. There were 66 males and 31 females aged 3 (1.8, 5.9) years. All the patients underwent perventricular device closure under the guidance of transesophageal echocardiography using eccentric occlusion device. Possible complications such as residual shunt, valvular regurgitation, atrioventricular conduction block and arrhythmias were recorded during the 1-year, 3-year and 5-year follow-up. Results All the patients received perventricular device closure successfully except that 1 patient underwent open surgical repair under cardiopulmonary bypass 3 months later because of the migration of device. So the rate of complete closure was 99.0%. No residual shunt, moderate or severe valvular regurgitation, atrioventricular conduction block or arrhythmias were observed 5 years later. Conclusion Treating subarterial ventricular septal defect through perventricular device closure exhibits remarkable mid-term efficacy, safety and feasibility with high success rate.
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Objective:To explore national standard of occupational skills for assistive technology consultants in China based on the study of relevant international standards. Methods:After analyzing the international and some other national job content, work requirements, professional education and vocational training, and vocational standards of assistive technology consultants, the national occupational skills standard for assistive technology consultants in China was established referring to the compiling rules of national occupational skills standard. Results:According to the compiling rules of national occupational skills standard, the national occupational skills standard for assistive technology consultants in China included career situation, basic requirements, job requirements, and weight table, etc. Conclusion:The vocational development, structural framework and content of professional capacity for assistive technology consultants are studied. The draft of national occupational skills standard for rehabilitation assistive technology consultants has been compiled.
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Objective:To analyze the compatibility rules of prescriptions containing Forsythiae Fructus based on data mining and explore the anti-inflammatory mechanism of Forsythiae Fructus based on network pharmacology，so as to provide reference for the rational clinical application of Forsythiae Fructus and the development of health foods and new Chinese medicines. Method:The prescriptions containing Forsythiae Fructus in the<italic> Dictionary of Traditional Chinese Medicine Prescriptions</italic> were collected，based on which a clinical prescription database was constructed. The Chinese herbs combined with Forsythiae Fructus and the corresponding indications were subjected to frequency statistics，association rule analysis，and complex network analysis using SPSS Statistics 26，IBM SPSS Modeler 18.0，and Gephi 9.2. The active components and targets of Forsythiae Fructus for anti-inflammation were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP），BATMAN-TCM，and SEA，and the targets related to anti-inflammation from GeneCards，Online Mendelian Inheritance in Man （OMIM），CTD，and GenCLiP3. Following the analysis of protein-protein interactions （PPI） with STRING，a PPI network was constructed. The enrichment analysis was performed using Metascape，and the active component-anti-inflammation target-signaling pathway network of Forsythiae Fructus was constructed by Cytoscape 3.8.2. Result:According to the inclusion and exclusion criteria，2 245 prescriptions containing Forsythiae Fructus were harvested，involving 512 Chinese herbs，with a total usage frequency of 27 314. The Chinese herbs that were most frequently combined with Forsythiae Fructus （>800 times） were Glycyrrhizae Radix et Rhizoma （1 483 times），Scutellariae Radix （964 times），and Angelicae Sinensis Radix （842 times）. Hence，the herbal pairs "Forsythiae Fructus-Scutellariae Radix" and "Forsythiae Fructus-Angelicae Sinensis Radix" were further explored. The prescriptions containing Forsythiae Fructus could be utilized for the treatment of 29 kinds of diseases，and three representative disease categories including "carbuncle，gangrene，sores and ulcers"，"ophthalmic diseases and syndromes" and "epidemic diseases" are selected for data mining. There were 19 association rules obtained with "Forsythiae Fructus-Glycyrrhizae Radix et Rhizoma-Lonicerae Japonicae Flos-Angelicae Sinensis Radix" as the core herb combination for "carbuncle，gangrene，sores and ulcers". The clustering analysis revealed one multi-herb clustering group，four herbal pairs，and single herb Lonicerae Japonicae Flos，the complex network analysis four herbal modules，and the factor analysis six common factors. There were 23 association rules obtained with "Forsythiae Fructus-Glycyrrhizae Radix et Rhizoma-Scutellariae Radix-Angelicae Sinensis Radix" as the core herb combination for "ophthalmic diseases and syndromes". The clustering analysis revealed two multi-herb clustering groups and four herbal pairs，the complex network analysis four herbal modules，and the factor analysis five common factors. There were 28 association rules obtained with "Forsythiae Fructus-Glycyrrhizae Radix et Rhizoma-Menthae Haplocalycis Herba-Lonicerae Japonicae Flos" as the core herb combination for "epidemic diseases". The clustering analysis revealed three multi-herb clustering groups，one herbal pair，and two single herbs Forsythiae Fructus and Glycyrrhizae Radix et Rhizoma，the complex network analysis four herbal modules，and the factor analysis five common factors. As demonstrated by network pharmacology-based analysis，the core anti-inflammation components of Forsythiae Fructus were quercetin，luteolin，and kaempferol，and the core targets were phosphoinositide-3-kinase regulatory subunit 1 （PIK3R1），protein kinase B 1 （Akt1），and epidermal growth factor receptor（EGFR）. The biological pathways were mainly concentrated in proteoglycans in cancer，pathways in cancer，and PI3K/Akt signaling pathway，with such functions as inhibition of transcription factors，regulation of enzyme activity，and inflammation-related gene expression involved. Conclusion:This study employed a variety of data mining techniques to objectively，intuitively，and scientifically uncover the compatibility rules of Forsythiae Fructus in the treatment of high-frequency diseases. It has been found that Forsythiae Fructus is often combined with heat-clearing herbs，tonifying herbs，exterior-releasing herbs，and blood-activating and stasis-resolving herbs for diverse diseases and syndromes. Under the premise of clearing heat and removing toxin，reinforcing healthy Qi and dredging stagnation are also emphasized. According to the degree of internal heat exuberance，the heat-clearing herbs with different merits are combined. This study has revealed the unique advantages of Forsythiae Fructus in the treatment of specific diseases and syndromes as well as its multi-component，multi-target，and multi-pathway mechanisms in anti-inflammation，breaking through the limitations in modern clinical and experimental research of Forsythiae Fructus. These findings are of great significance for guiding the rational clinical application of Forsythiae Fructus and the development of health foods and new Chinese medicines，thus better accelerating the development of Chinese medicine health industry.