Objective:To explore the clinical application value of a combined model based on the radiomics features of magnetic resonance imaging(MRI)and MRI signs in predicting recurrence after radical resection for hepatocellular carcinoma(HCC).Methods:A retrospective analysis was conducted on the imaging data of 100 patients with radical resection for HCC who admitted to Zibo 148 Hospital from May 2016 to May 2020.All patients underwent abdominal enhanced MRI examination before surgery,and they were followed up for at least 2 years after the surgery.They were randomly divided into training group(70 cases)and verification group(30 cases)as a ratio of 7:3.According to the postoperative follow-up results,the training group existed 12 cases of recurrence and 58 cases without recurrence,and the verification group existed 5 cases of recurrence and 25 cases without recurrence.The 3D-slicer software was used to extract radiomics features of preoperative MRI images of each HCC patient.The intra-group correlation coefficient(ICC)of the extracted imaging features of the observers was calculated.The maximum related minimum redundancy(mRMR)algorithm and LASSO regression were selected to analyze the established radiomics labels after dimensionality reduction and screening.Univariate and multivariate logistic regression analysis were used to screen the independent risk factors of predicting recurrence in MRI signs,and they were used respectively to construct radiomics models with the radiomics labels of plain scan,arterial phase,portal phase and hepatobiliary phase.The receiver operating characteristic(ROC)curve was used to assess the diagnostic efficacy of each radiomics model in predicting recurrence.Results:The ICC range of two physicians in selecting radiomics features from the MRI images of all patients were between 0.903 and 0.957,which consistency was favorable(ICC≥0.9).Compared with other predictive models,the highest area under curve(AUC)values of ROC curve of the radiomics model of plain scan of training group[0.951(95%CI:0.901-1.000)]and verification group[0.968(95%CI:0.917-1.000)]were respectively 0.951 and 0.968 in predicting recurrence after radical resection for liver cancer.Conclusion:The combined model that is constructed on the basis of MRI radiomics features has favorable predictive value for the recurrence of patients after radical resection for HCC.Among of them,the radiomics model of plain scan has a certain guiding role in the clinical implementation of personalized treatment plans under the absence of enhancement,and in underdeveloped areas.

Cholesterol is a crucial lipid in the human body.Elevated levels of cholesterol can result in condi-tions such as hypercholesterolemia.3-hydroxy-3-methylglutaryl coenzyme A reductase(HMGCR)serves as a pivotal en-zyme in the synthesis of cholesterol,acting as a rate-limiting factor.As a result,HMGCR plays a critical role in maintain-ing cholesterol balance,with the regulatory processes being intricate in vivo.This review outlines the advancements in un-derstanding the regulatory mechanisms of HMGCR,encompassing transcriptional control,degradation pathways,and en-zyme activity.

Objective:To explore the clinical application value of a combined model based on the radiomics features of magnetic resonance imaging(MRI)and MRI signs in predicting recurrence after radical resection for hepatocellular carcinoma(HCC).Methods:A retrospective analysis was conducted on the imaging data of 100 patients with radical resection for HCC who admitted to Zibo 148 Hospital from May 2016 to May 2020.All patients underwent abdominal enhanced MRI examination before surgery,and they were followed up for at least 2 years after the surgery.They were randomly divided into training group(70 cases)and verification group(30 cases)as a ratio of 7:3.According to the postoperative follow-up results,the training group existed 12 cases of recurrence and 58 cases without recurrence,and the verification group existed 5 cases of recurrence and 25 cases without recurrence.The 3D-slicer software was used to extract radiomics features of preoperative MRI images of each HCC patient.The intra-group correlation coefficient(ICC)of the extracted imaging features of the observers was calculated.The maximum related minimum redundancy(mRMR)algorithm and LASSO regression were selected to analyze the established radiomics labels after dimensionality reduction and screening.Univariate and multivariate logistic regression analysis were used to screen the independent risk factors of predicting recurrence in MRI signs,and they were used respectively to construct radiomics models with the radiomics labels of plain scan,arterial phase,portal phase and hepatobiliary phase.The receiver operating characteristic(ROC)curve was used to assess the diagnostic efficacy of each radiomics model in predicting recurrence.Results:The ICC range of two physicians in selecting radiomics features from the MRI images of all patients were between 0.903 and 0.957,which consistency was favorable(ICC≥0.9).Compared with other predictive models,the highest area under curve(AUC)values of ROC curve of the radiomics model of plain scan of training group[0.951(95%CI:0.901-1.000)]and verification group[0.968(95%CI:0.917-1.000)]were respectively 0.951 and 0.968 in predicting recurrence after radical resection for liver cancer.Conclusion:The combined model that is constructed on the basis of MRI radiomics features has favorable predictive value for the recurrence of patients after radical resection for HCC.Among of them,the radiomics model of plain scan has a certain guiding role in the clinical implementation of personalized treatment plans under the absence of enhancement,and in underdeveloped areas.

Cholesterol is a crucial lipid in the human body.Elevated levels of cholesterol can result in condi-tions such as hypercholesterolemia.3-hydroxy-3-methylglutaryl coenzyme A reductase(HMGCR)serves as a pivotal en-zyme in the synthesis of cholesterol,acting as a rate-limiting factor.As a result,HMGCR plays a critical role in maintain-ing cholesterol balance,with the regulatory processes being intricate in vivo.This review outlines the advancements in un-derstanding the regulatory mechanisms of HMGCR,encompassing transcriptional control,degradation pathways,and en-zyme activity.

Objective To investigate the expression of Toll-like receptor 2(TLR2)and Toll-like receptor 4(TLR4)in peripheral blood mononuclear cells(PBMC)in children with recurrent respiratory tract infection(RRTI)and its relationship with T helper cell 1(Th1)/T helper cell 2(Th2)immune response.Methods A total of 65 children diagnosed with RRTI who admitted to the hospital from December 2020 to December 2022 were enrolled in the study as the RRTI group,and 45 healthy children who underwent physical examination in the hospital during the same period were enrolled as the control group.The relative expression levels of TLR2 and TLR4 mRNA in PBMCs were detected by real-time fluorescence quantitative PCR(qPCR).The expres-sion rates of TLR2 and TLR4 protein in PBMCs were detected by flow cytometry.The levels of Th1 cytokine interferon-γ(IFN-γ),Th2 cytokine interleukin-4(IL-4)and their ratio(IFN-γ/IL-4)in plasma were detected by enzyme-linked immunosorbent assay(ELISA).Pearson correlation analysis was used to analyze the corre-lation between TLR2,TLR4 protein expression rates and plasma IFN-γ,IL-4 levels.Results The RRTI group had significantly higher plasma level of Th2 cytokine IL-4 than the control group,significantly lower plasma level of Th1 cytokine IFN-y than the control group,and significantly lower ratio of IFN-γ/IL-4 than the con-trol group,the differences were all statistically significant(P＜0.05).The relative expression levels of TLR2 and TLR4 mRNA and protein expression rates in PBMC of children in the RRTI group were higher than those in the control group,and the differences were statistically significant(P＜0.05).Pearson correlation analysis showed that the protein expression rates of TLR2 and TLR4 in PBMC of children with RRTI were both nega-tively correlated with both plasma IFN-γ levels and IFN-γ/IL-4(P＜0.05)and positively correlated with plasma IL-4 levels(P＜0.05).Conclusion The expression of TLR2 and TLR4 in PBMC and plasma Th1/Th2 cytokines in children with RRTI may be involved in the occurrence and development of the disease.Ex-cessive activation of TLR2 and TLR4 may weaken Th1 function and enhance Th2 function.

Objective:To explore the predictive value of thrombus markers for venous thromboembolism (VTE) in patients with malignant tumors after surgery.Methods:The clinical data of 150 patients with malignant tumors after surgery admitted to Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine in Hebei Province from July 2020 to February 2021 were retrospectively analyzed. All 150 patients followed-up for 4 weeks were treated as the observation group, including 30 cases with VTE (the thrombosis group) and 120 cases without VTE (the non-thrombosis group). Another 60 cases undergoing healthy physical examination during the same period were selected as the control group. The chemiluminescence immunoassay was used to detect thrombin-antithrombin complex (TAT), plasmin-α 2 plasmin inhibitor complex (PIC), thrombomodulin (TM), tissue-type plasminogen activator inhibitor-1 complex(tPAIC). The control group was tested once, and the observation group was tested on the 1 day before the operation and 1 day after the operation. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of thrombus markers for VTE in patients with malignant tumors after surgery. Results:The patients with lung cancer ( χ2 = 12.53, P = 0.014), ≥ 60 years old ( χ2 = 6.66, P = 0.036),body mass index>30 kg/m 2 ( χ2 = 40.53, P<0.001), tumor metastasis ( χ2 = 5.38, P = 0.031), Ⅲ-Ⅳ stage ( χ2 = 5.83, P = 0.023) had higher incidence of VTE after the operation, and the difference was statistically significant. The levels of TAT, PIC and TM in the observation group were higher than those in the control group (all P < 0.05).The levels of TAT and TM in the thrombosis group were higher than those in the non-thrombosis group before the operation, and the difference was statistically significant (all P < 0.05).The value of TM in predicting VTE was high [the best cut-off value was 10.70 TU/ml, area under the curve (AUC) was 0.786, the sensitivity was 73.30%, the specificity was 81.70%], the combination of TAT and TM could improve the predictive value (AUC was 0.796, the sensitivity was 80.00%, the specificity was 77.50%). The levels of TAT, PIC, TM and tPAIC in thrombosis group were all higher than those in the non-thrombosis group after the operation, and the difference was statistically significant (all P < 0.05). The value of TAT in predicting VTE was high (the best cut-off value was 16.50 ng/ml, AUC was 0.887, the sensitivity was 82.36%, the specificity was 71.65%), the combination of TAT, PIC, TM and tPAIC could improve the predictive value (AUC was 0.913, the sensitivity was 90.00%, the specificity was 88.60%). The level of PIC was positively correlated with TAT before and after the operation ( r = 0.66, P < 0.001; r = 0.64, P < 0.001). Conclusions:TM can be used as a sensitive indicator in the early prediction of VTE for the patients with malignant tumors and it aims at the prevention; TAT can be used as a specific indicator in predicting the development of VTE and it aims at the intervention in time. The combined detection of TAT, PIC, TM and tPAIC can improve the predictive value of VTE. At the same time, PIC can be used to evaluate the risk of bleeding.

Protein-RNA interaction networks are essential to understand gene regulation control. Identifying binding sites of RNA-binding proteins (RBPs) by the UV-crosslinking and immunoprecipitation (CLIP) represents one of the most powerful methods to map protein-RNA interactions in vivo. However, the traditional CLIP protocol is technically challenging, which requires radioactive labeling and suffers from material loss during PAGE-membrane transfer procedures. Here we introduce a super-efficient CLIP method (GoldCLIP) that omits all gel purification steps. This nonisotopic method allows us to perform highly reproducible CLIP experiments with polypyrimidine tract-binding protein (PTB), a classical RBP in human cell lines. In principle, our method guarantees sequencing library constructions, providing the protein of interest can be successfully crosslinked to RNAs in living cells. GoldCLIP is readily applicable to diverse proteins to uncover their endogenous RNA targets.
Binding Sites ; Cell Line ; Heterogeneous-Nuclear Ribonucleoproteins ; isolation & purification ; metabolism ; Humans ; Immunoprecipitation ; methods ; Polypyrimidine Tract-Binding Protein ; isolation & purification ; metabolism ; RNA ; isolation & purification ; metabolism ; RNA-Binding Proteins ; isolation & purification ; metabolism

Objective To investigate the changes of platelet reactivity and its influencing factors after aspirin treatment in patients with ischemic stroke complicated with diabetes. Methods From September 2016to December 2017, patients with acute ischemic stroke admitted to the Department of Neurology, Weihai Municipal Hospital within 24 h of onset were enrolled. All patients took aspirin (100 mg/d) within 24 h ofadmission, and after taking the drug (7 ±2 d), the PL-11 platelet function analyzer was used to determine the maximum platelet aggregation ratio (MAR) induced by arachidonic acid (AA). The baseline data of the patients were documented. The factors affecting high platelet reactivity (HPR) were analyzed. Results A total of 398 patients with ischemic stroke were enrolled, including 137 in the diabetes group and 261 in the non-diabetes group. MARAA (43. 45％ ± 14. 11％ vs. 31. 55％ ± 19. 39％; t = 6. 996, P < 0. 001) and the incidence of HPR (34. 3％ vs. 19. 9％; χ2 = 9. 946, P = 0. 002) in the diabetes group were significantly higher than in those in the non-diabetes group. Of the 137 patients with ischemic stroke complicated with diabetes, 47 had HPR. The proportions of patients with hyperlipidemia, previous history of stroke or transient ischemic attack and baseline NIHSS score, HOMA-IR (homeostatis model assessment-insulin resistance),high-sensitivity C-reactive protein, fasting blood glucose, and glycosylated hemoglobin in the HPR group were significantly higher than those in the non-HPR group (all P < 0. 05). Multivariate logistic regression analysis showed that HOMA-IR (odds ratio [OR] 1. 153, 95％ confidence interval [CI] 1. 027-1. 295; P =0. 016), high-sensitivity C-reactive protein (OR 9. 416, 95％ CI 2. 271-39. 049; P = 0. 002), fasting blood glucose (OR 1. 125, 95％ CI 1. 025-1. 235; P = 0. 013), and glycosylated hemoglobin (OR 1. 458, 95％ CI 1. 170-1. 816; P = 0. 001) were the independent risk factors for HPR. Conclusion The platelet reactivity during aspirin therapy in patients with ischemic stroke complicated with diabetes mellitus was high, and platelet activity was associated with multiple mechanisms, such as inflammation, insulin resistance, and hyperglycemia.

RNA-binding protein exerts important biological function by specifically recognizing RNA motif. SELEX (Systematic evolution of ligands by exponential enrichment), an in vitro selection method, can obtain consensus motif with high-affinity and specificity for many target molecules from DNA or RNA libraries. Here, we combined SELEX with next-generation sequencing to study the protein-RNA interaction in vitro. A pool of RNAs with 20 bp random sequences were transcribed by T7 promoter, and target protein was inserted into plasmid containing SBP-tag, which can be captured by streptavidin beads. Through only one cycle, the specific RNA motif can be obtained, which dramatically improved the selection efficiency. Using this method, we found that human hnRNP A1 RRMs domain (UP1 domain) bound RNA motifs containing AGG and AG sequences. The EMSA experiment indicated that hnRNP A1 RRMs could bind the obtained RNA motif. Taken together, this method provides a rapid and effective method to study the RNA binding specificity of proteins.
Aptamers, Nucleotide ; Gene Library ; Heterogeneous Nuclear Ribonucleoprotein A1 ; genetics ; High-Throughput Nucleotide Sequencing ; Humans ; RNA ; SELEX Aptamer Technique